A comprehensive overview of drug delivery systems for tumor treatment

Nasser Ali Alhabib; Soliman Mohammed Alehaidib; Mohammed Ahmed Almansour; Mubarak Saad Aldosary; Maysam Taysir Almegbel; Ahlam Mohammed Alzahrani

doi:10.53730/ijhs.v5nS1.15039

Authors

Nasser Ali Alhabib KSA, National Guard Health Affairs
Soliman Mohammed Alehaidib KSA, National Guard Health Affairs
Mohammed Ahmed Almansour KSA, National Guard Health Affairs
Mubarak Saad Aldosary KSA, National Guard Health Affairs
Maysam Taysir Almegbel KSA, National Guard Health Affairs
Ahlam Mohammed Alzahrani KSA, National Guard Health Affairs

Keywords:

Drug delivery systems, cancer therapy, nanomedicine, pegylated liposomes, ferritin, exosomes, dendrimers

Abstract

Background: With 19.3 million new cancer cases and 10 million related deaths globally in 2020, there is an urgent need for effective cancer treatments. Traditional modalities such as surgery, radiotherapy, and chemotherapy have limitations, particularly for aggressive and metastatic cancers, leading to high recurrence rates and poor outcomes. The development of advanced drug delivery systems (DDS) is emerging as a promising strategy to enhance treatment efficacy and reduce side effects. Aim: This review aims to provide a comprehensive overview of the various drug delivery systems employed in tumor treatment, highlighting their preparation, characteristics, applications, and clinical potential. Methods: The review covers a range of drug delivery carriers including nonmetallic nanoparticles, metal nanoparticles, albumin, ferritin, liposomes, exosomes, and dendrimers. The focus is on their design, functionalization, and effectiveness in delivering antitumor drugs. Additionally, it discusses the integration of various anticancer agents with these delivery systems and their impact on treatment efficacy. Results: Recent advancements in DDS have shown significant improvements in drug targeting and delivery. For instance, second-generation nanomedicines with active targeting mechanisms have demonstrated enhanced specificity and reduced systemic toxicity. Notable developments include pegylated liposomal doxorubicin, ferritin-based drug carriers, and exosome-sheathed nanoparticles.

Downloads

Download data is not yet available.

References

Ahmad, N., Sharma, S., Alam, M. K., Singh, V. N., Shamsi, S. F., Mehta, B. R., et al. (2010). Rapid Synthesis of Silver Nanoparticles Using Dried Medicinal Plant of Basil. Colloids Surf. B. Biointerfaces 81, 81–86. doi:10.1016/j.colsurfb.2010.06.029

Alomrani, A., Badran, M., Harisa, G. I., ALshehry, M., Alshamsan, A., Alkholief, M., et al. (2019). The Use of Chitosan-Coated Flexible Liposomes as a Remarkable Carrier to Enhance the Antitumor Efficacy of 5-fluorouracil against Colorectal Cancer. Saudi Pharm. J. 27, 603–611. doi:10.1016/j.jsps.2019.02.008

Anitha, A., Chennazhi, K. P., Nair, S. V., and Jayakumar, R. (2012a). 5-flourouracil Loaded N,O-carboxymethyl Chitosan Nanoparticles as an Anticancer Nanomedicine for Breast Cancer. J. Biomed. Nanotechnol 8, 29–42. doi:10.1166/jbn.2012.1365

Anitha, A., Maya, S., Deepa, N., Chennazhi, K. P., Nair, S. V., and Jayakumar, R. (2012b). Curcumin-loaded N,O-carboxymethyl Chitosan Nanoparticles for Cancer Drug Delivery. J. Biomater. Sci. Polym. Ed. 23, 1381–1400. doi:10.1163/092050611x581534

Anitha, A., Sreeranganathan, M., Chennazhi, K. P., Lakshmanan, V. K., and Jayakumar, R. (2014). In Vitro combinatorial Anticancer Effects of 5-fluorouracil and Curcumin Loaded N,O-carboxymethyl Chitosan Nanoparticles toward colon Cancer and In Vivo Pharmacokinetic Studies. Eur. J. Pharm. Biopharm. 88, 238–251. doi:10.1016/j.ejpb.2014.04.017

Anitha, A., Divya Rani, V. V., Krishna, R., Sreeja, V., Selvamurugan, N., Nair, S. V., et al. (2009). Synthesis, Characterization, Cytotoxicity and Antibacterial Studies of Chitosan, O-Carboxymethyl and N,O-carboxymethyl Chitosan Nanoparticles. Carbohydr. Polym. 78, 672–677. doi:10.1016/j.carbpol.2009.05.028

Aydın, B., Uçar, E., Tekin, V., İçhedef, Ç., and Teksöz, S. (2020). Biocompatible Delivery System for Metformin: Characterization, Radiolabeling and In Vitro Studies. Anticancer Agents Med. Chem. 20, 1626–1634. doi:10.2174/1871520620666200423081235

Baetke, S. C., Lammers, T., and Kiessling, F. (2015). Applications of Nanoparticles for Diagnosis and Therapy of Cancer. Br. J. Radiol. 88, 20150207. doi:10.1259/bjr.20150207

Bai, J., Duan, J., Liu, R., Du, Y., Luo, Q., Cui, Y., et al. (2020). Engineered Targeting tLyp-1 Exosomes as Gene Therapy Vectors for Efficient Delivery of siRNA into Lung Cancer Cells. Asian J. Pharm. Sci. 15, 461–471. doi:10.1016/j.ajps.2019.04.002

Batrakova, E. V., and Kim, M. S. (2015). Using Exosomes, Naturally-Equipped Nanocarriers, for Drug Delivery. J. Control Release 219, 396–405. doi:10.1016/j.jconrel.2015.07.030

Bingham, R. J., Olmsted, P. D., and Smye, S. W. (2010). Undulation Instability in a Bilayer Lipid Membrane Due to Electric Field Interaction with Lipid Dipoles. Phys. Rev. E Stat. Nonlin Soft Matter Phys. 81, 051909. doi:10.1103/PhysRevE.81.051909

Bishop, A. J., Zagars, G. K., Torres, K. E., Bird, J. E., Feig, B. W., and Guadagnolo, B. A. (2018). Malignant Peripheral Nerve Sheath Tumors: A Single Institution's Experience Using Combined Surgery and Radiation Therapy. Am. J. Clin. Oncol. 41, 465–470. doi:10.1097/coc.0000000000000303

Calisti, L., Trabuco, M. C., Boffi, A., Testi, C., Montemiglio, L. C., des Georges, A., et al. (2018). Engineered Ferritin for Lanthanide Binding. PLoS One 13, e0201859. doi:10.1371/journal.pone.0201859

Carvalho, C., Santos, R. X., Cardoso, S., Correia, S., Oliveira, P. J., Santos, M. S., et al. (2009). Doxorubicin: the Good, the Bad and the Ugly Effect. Curr. Med. Chem. 16, 3267–3285. doi:10.2174/092986709788803312

Chauhan, A. S. (2015). Dendrimer Nanotechnology for Enhanced Formulation and Controlled Delivery of Resveratrol. Ann. N. Y. Acad. Sci. 1348, 134–140. doi:10.1111/nyas.12816

Chauhan, A. S. (2018). Dendrimers for Drug Delivery. Molecules 23, 938. doi:10.3390/molecules23040938

Chen, C., Lu, L., Yan, S., Yi, H., Yao, H., Wu, D., et al. (2018). Autophagy and Doxorubicin Resistance in Cancer. Anticancer Drugs 29, 1–9. doi:10.1097/cad.0000000000000572

Chen, J., Dou, Y., Tang, Y., and Zhang, X. (2020). Folate Receptor-Targeted RNAi Nanoparticles for Silencing STAT3 in Tumor-Associated Macrophages and Tumor Cells. Nanomedicine 25, 102173. doi:10.1016/j.nano.2020.102173

Chen, X., Zhang, Y., Tang, C., Tian, C., Sun, Q., Su, Z., et al. (2017). Co-delivery of Paclitaxel and Anti-survivin siRNA via Redox-Sensitive Oligopeptide Liposomes for the Synergistic Treatment of Breast Cancer and Metastasis. Int. J. Pharm. 529, 102–115. doi:10.1016/j.ijpharm.2017.06.071

Chen, Y. C., Huang, X. C., Luo, Y. L., Chang, Y. C., Hsieh, Y. Z., and Hsu, H. Y. (2013). Non-metallic Nanomaterials in Cancer Theranostics: a Review of Silica- and Carbon-Based Drug Delivery Systems. Sci. Technol. Adv. Mater. 14, 044407. doi:10.1088/1468-6996/14/4/044407

Chinnaiyan, S. K., Soloman, A. M., Perumal, R. K., Gopinath, A., and Balaraman, M. (2019). 5 Fluorouracil-Loaded Biosynthesised Gold Nanoparticles for the In Vitro Treatment of Human Pancreatic Cancer Cell. IET Nanobiotechnol 13, 824–828. doi:10.1049/iet-nbt.2019.0007

Cho, H. S., Dong, Z., Pauletti, G. M., Zhang, J., Xu, H., Gu, H., et al. (2010). Fluorescent, Superparamagnetic Nanospheres for Drug Storage, Targeting, and Imaging: a Multifunctional Nanocarrier System for Cancer Diagnosis and Treatment. ACS Nano 4, 5398–5404. doi:10.1021/nn101000e

Damiani, V., Falvo, E., Fracasso, G., Federici, L., Pitea, M., De Laurenzi, V., et al. (2017). Therapeutic Efficacy of the Novel Stimuli-Sensitive Nano-Ferritins Containing Doxorubicin in a Head and Neck Cancer Model. Int. J. Mol. Sci. 18, 1555. doi:10.3390/ijms18071555

De, A., Kuppuswamy, G., and Jaiswal, A. (2019). Implementation of Two Different Experimental Designs for Screening and Optimization of Process Parameters for Metformin-Loaded Carboxymethyl Chitosan Formulation. Drug Dev. Ind. Pharm. 45, 1821–1834. doi:10.1080/03639045.2019.1665060

de Weger, V. A., Beijnen, J. H., and Schellens, J. H. (2014). Cellular and Clinical Pharmacology of the Taxanes Docetaxel and Paclitaxel-Aa Review. Anticancer Drugs 25, 488–494. doi:10.1097/cad.0000000000000093

Durán, N., Durán, M., de Jesus, M. B., Seabra, A. B., Fávaro, W. J., and Nakazato, G. (2016). Silver Nanoparticles: A New View on Mechanistic Aspects on Antimicrobial Activity. Nanomedicine 12, 789–799. doi:10.1016/j.nano.2015.11.016

Falvo, E., Tremante, E., Arcovito, A., Papi, M., Elad, N., Boffi, A., et al. (2016). Improved Doxorubicin Encapsulation and Pharmacokinetics of Ferritin-Fusion Protein Nanocarriers Bearing Proline, Serine, and Alanine Elements. Biomacromolecules 17, 514–522. doi:10.1021/acs.biomac.5b01446

Feng, L., Wu, L., and Qu, X. (2013). New Horizons for Diagnostics and Therapeutic Applications of Graphene and Graphene Oxide. Adv. Mater. 25, 168–186. doi:10.1002/adma.201203229

Feng, T., Wei, Y., Lee, R. J., and Zhao, L. (2017). Liposomal Curcumin and its Application in Cancer. Int. J. Nanomedicine 12, 6027–6044. doi:10.2147/ijn.S132434

Fracasso, G., Falvo, E., Colotti, G., Fazi, F., Ingegnere, T., Amalfitano, A., et al. (2016). Selective Delivery of Doxorubicin by Novel Stimuli-Sensitive Nano-Ferritins Overcomes Tumor Refractoriness. J. Control Release 239, 10–18. doi:10.1016/j.jconrel.2016.08.010

Fu, L., Sun, Y., Ding, L., Wang, Y., Gao, Z., Wu, Z., et al. (2016). Mechanism Evaluation of the Interactions between Flavonoids and Bovine Serum Albumin Based on Multi-Spectroscopy, Molecular Docking and Q-TOF HR-MS Analyses. Food Chem. 203, 150–157. doi:10.1016/j.foodchem.2016.01.105

Gajendiran, M., Jo, H., Kim, K., and Balasubramanian, S. (2019). Green Synthesis of Multifunctional PEG-Carboxylate π Back-Bonded Gold Nanoconjugates for Breast Cancer Treatment. Int. J. Nanomedicine 14, 819–834. doi:10.2147/ijn.S190946

Ganeshkumar, M., Ponrasu, T., Raja, M. D., Subamekala, M. K., and Suguna, L. (2014). Green Synthesis of Pullulan Stabilized Gold Nanoparticles for Cancer Targeted Drug Delivery. Spectrochim Acta A. Mol. Biomol. Spectrosc. 130, 64–71. doi:10.1016/j.saa.2014.03.097

Greco, K. A., Franzen, C. A., Foreman, K. E., Flanigan, R. C., Kuo, P. C., and Gupta, G. N. (2016). PLK-1 Silencing in Bladder Cancer by siRNA Delivered with Exosomes. Urology 91, 241–247. doi:10.1016/j.urology.2016.01.028

Guo, J., O'Driscoll, C. M., Holmes, J. D., and Rahme, K. (2016). Bioconjugated Gold Nanoparticles Enhance Cellular Uptake: A Proof of Concept Study for siRNA Delivery in Prostate Cancer Cells. Int. J. Pharm. 509, 16–27. doi:10.1016/j.ijpharm.2016.05.027

Guo, J., Yang, W., and Wang, C. (2005). Systematic Study of the Photoluminescence Dependence of Thiol-Capped CdTe Nanocrystals on the Reaction Conditions. J. Phys. Chem. B 109, 17467–17473. doi:10.1021/jp044770z

Guo, J., Yang, W., Wang, C., He, J., and Chen, J. (2006). Poly(N-isopropylacrylamide)-Coated Luminescent/Magnetic Silica Microspheres: Preparation, Characterization, and Biomedical Applications. Chem. Mater. 18, 5554–5562. doi:10.1021/cm060976w

Haghiralsadat, F., Amoabediny, G., Naderinezhad, S., Forouzanfar, T., Helder, M. N., and Zandieh-Doulabi, B. (2018). Preparation of PEGylated Cationic Nanoliposome-siRNA Complexes for Cancer Therapy. Artif. Cells Nanomed Biotechnol 46, 684–692. doi:10.1080/21691401.2018.1434533

Hanan, N. A., Chiu, H. I., Ramachandran, M. R., Tung, W. H., Mohamad Zain, N. N., Yahaya, N., et al. (2018). Cytotoxicity of Plant-Mediated Synthesis of Metallic Nanoparticles: A Systematic Review. Int. J. Mol. Sci. 19, 1725. doi:10.3390/ijms19061725

Handali, S., Moghimipour, E., Kouchak, M., Ramezani, Z., Amini, M., Angali, K. A., et al. (2019). New Folate Receptor Targeted Nano Liposomes for Delivery of 5-fluorouracil to Cancer Cells: Strong Implication for Enhanced Potency and Safety. Life Sci. 227, 39–50. doi:10.1016/j.lfs.2019.04.030

Handali, S., Moghimipour, E., Rezaei, M., Ramezani, Z., Kouchak, M., Amini, M., et al. (2018). A Novel 5-Fluorouracil Targeted Delivery to colon Cancer Using Folic Acid Conjugated Liposomes. Biomed. Pharmacother. 108, 1259–1273. doi:10.1016/j.biopha.2018.09.128

Harrington, K. J., Mohammadtaghi, S., Uster, P. S., Glass, D., Peters, A. M., Vile, R. G., et al. (2001). Effective Targeting of Solid Tumors in Patients with Locally Advanced Cancers by Radiolabeled Pegylated Liposomes. Clin. Cancer. Res. 7, 243–254.

Hatamie, S., Akhavan, O., Sadrnezhaad, S. K., Ahadian, M. M., Shirolkar, M. M., and Wang, H. Q. (2015). Curcumin-reduced Graphene Oxide Sheets and Their Effects on Human Breast Cancer Cells. Mater. Sci. Eng. C Mater. Biol. Appl. 55, 482–489. doi:10.1016/j.msec.2015.05.077

Huang, Y., Hu, L., Huang, S., Xu, W., Wan, J., Wang, D., et al. (2018). Curcumin-loaded Galactosylated BSA Nanoparticles as Targeted Drug Delivery Carriers Inhibit Hepatocellular Carcinoma Cell Proliferation and Migration. Int. J. Nanomedicine 13, 8309–8323. doi:10.2147/ijn.S184379

Hurtado-Gallego, J., Leganés, F., Rosal, R., and Fernández-Piñas, F. (2019). Use of Cyanobacterial Luminescent Bioreporters to Report on the Environmental Impact of Metallic Nanoparticles. Sensors (Basel) 19, 3597. doi:10.3390/s19163597

Ji, A., Zhang, Y., Lv, G., Lin, J., Qi, N., Ji, F., et al. (2018). 131 I Radiolabeled Immune Albumin Nanospheres Loaded with Doxorubicin for In Vivo Combinatorial Therapy. J. Labelled Comp. Radiopharm. 61, 362–369. doi:10.1002/jlcr.3593

Jose, A., Labala, S., Ninave, K. M., Gade, S. K., and Venuganti, V. V. K. (2018). Effective Skin Cancer Treatment by Topical Co-delivery of Curcumin and STAT3 siRNA Using Cationic Liposomes. AAPS PharmSciTech 19, 166–175. doi:10.1208/s12249-017-0833-y

Jose, P., Sundar, K., Anjali, C. H., and Ravindran, A. (2015). Metformin-loaded BSA Nanoparticles in Cancer Therapy: a New Perspective for an Old Antidiabetic Drug. Cell Biochem Biophys 71, 627–636. doi:10.1007/s12013-014-0242-8

Julien, D. C., Behnke, S., Wang, G., Murdoch, G. K., and Hill, R. A. (2011). Utilization of Monoclonal Antibody-Targeted Nanomaterials in the Treatment of Cancer. MAbs 3, 467–478. doi:10.4161/mabs.3.5.16089

Kamerkar, S., LeBleu, V. S., Sugimoto, H., Yang, S., Ruivo, C. F., Melo, S. A., et al. (2017). Exosomes Facilitate Therapeutic Targeting of Oncogenic KRAS in Pancreatic Cancer. Nature 546, 498–503. doi:10.1038/nature22341

Kaminskas, L. M., Kelly, B. D., McLeod, V. M., Sberna, G., Owen, D. J., Boyd, B. J., et al. (2011). Characterisation and Tumour Targeting of PEGylated Polylysine Dendrimers Bearing Doxorubicin via a pH Labile Linker. J. Control Release 152, 241–248. doi:10.1016/j.jconrel.2011.02.005

Karimi, M., Bahrami, S., Ravari, S. B., Zangabad, P. S., Mirshekari, H., Bozorgomid, M., et al. (2016). Albumin Nanostructures as Advanced Drug Delivery Systems. Expert Opin. Drug Deliv. 13, 1609–1623.

Kulhari, H., Pooja, D., Shrivastava, S., Kuncha, M., Naidu, V. G. M., Bansal, V., et al. (2016). Trastuzumab-grafted PAMAM Dendrimers for the Selective Delivery of Anticancer Drugs to HER2-Positive Breast Cancer. Sci. Rep. 6, 23179. doi:10.1038/srep23179

Kumar, C. S., Raja, M. D., Sundar, D. S., Gover Antoniraj, M., and Ruckmani, K. (2015). Hyaluronic Acid Co-functionalized Gold Nanoparticle Complex for the Targeted Delivery of Metformin in the Treatment of Liver Cancer (HepG2 Cells). Carbohydr. Polym. 128, 63–74. doi:10.1016/j.carbpol.2015.04.010

Kumar, K., Vulugundam, G., Jaiswal, P. K., Shyamlal, B. R. K., and Chaudhary, S. (2017). Efficacious Cellular Codelivery of Doxorubicin and EGFP siRNA Mediated by the Composition of PLGA and PEI Protected Gold Nanoparticles. Bioorg. Med. Chem. Lett. 27, 4288–4293. doi:10.1016/j.bmcl.2017.08.037

Kuruvilla, S. P., Tiruchinapally, G., ElAzzouny, M., and ElSayed, M. E. (2017). N-Acetylgalactosamine-Targeted Delivery of Dendrimer-Doxorubicin Conjugates Influences Doxorubicin Cytotoxicity and Metabolic Profile in Hepatic Cancer Cells. Adv. Healthc. Mater. 6, 1601046. doi:10.1002/adhm.201601046

Lamichhane, S., and Lee, S. (2020). Albumin Nanoscience: Homing Nanotechnology Enabling Targeted Drug Delivery and Therapy. Arch. Pharm. Res. 43, 118–133. doi:10.1007/s12272-020-01204-7

Lammers, T., Rizzo, L. Y., Storm, G., and Kiessling, F. (2012). Personalized Nanomedicine. Clin. Cancer Res. 18, 4889–4894. doi:10.1158/1078-0432.Ccr-12-1414

Landgraf, M., Lahr, C. A., Kaur, I., Shafiee, A., Sanchez-Herrero, A., Janowicz, P. W., et al. (2020). Targeted Camptothecin Delivery via Silicon Nanoparticles Reduces Breast Cancer Metastasis. Biomaterials 240, 119791. doi:10.1016/j.biomaterials.2020.119791

Laomeephol, C., Ferreira, H., Kanokpanont, S., Neves, N. M., Kobayashi, H., and Damrongsakkul, S. (2020). Dual-functional Liposomes for Curcumin Delivery and Accelerating Silk Fibroin Hydrogel Formation. Int. J. Pharm. 589, 119844. doi:10.1016/j.ijpharm.2020.119844

Leboffe, L., di Masi, A., Polticelli, F., Trezza, V., and Ascenzi, P. (2020). Structural Basis of Drug Recognition by Human Serum Albumin. Curr. Med. Chem. 27, 4907–4931. doi:10.2174/0929867326666190320105316

Lee, J. Y., Shin, D. H., and Kim, J. S. (2019). Anticancer Effect of Metformin in Herceptin-Conjugated Liposome for Breast Cancer. Pharmaceutics 12, 11. doi:10.3390/pharmaceutics12010011

Lee, S. J., Kim, M. J., Kwon, I. C., and Roberts, T. M. (2016). Delivery Strategies and Potential Targets for siRNA in Major Cancer Types. Adv. Drug Deliv. Rev. 104, 2–15. doi:10.1016/j.addr.2016.05.010

Li, D., Yao, S., Zhou, Z., Shi, J., Huang, Z., and Wu, Z. (2020a). Hyaluronan Decoration of Milk Exosomes Directs Tumor-specific Delivery of Doxorubicin. Carbohydr. Res. 493, 108032. doi:10.1016/j.carres.2020.108032

Li, L. S., Ren, B., Yang, X., Cai, Z. C., Zhao, X. J., and Zhao, M. X. (2021). Hyaluronic Acid-Modified and Doxorubicin-Loaded Gold Nanoparticles and Evaluation of Their Bioactivity. Pharmaceuticals (Basel) 14, 101. doi:10.3390/ph14020101

Li, R., Lin, Z., Zhang, Q., Zhang, Y., Liu, Y., Lyu, Y., et al. (2020b). Injectable and In Situ-Formable Thiolated Chitosan-Coated Liposomal Hydrogels as Curcumin Carriers for Prevention of In Vivo Breast Cancer Recurrence. ACS Appl. Mater. Inter. 12, 17936–17948. doi:10.1021/acsami.9b21528

Li, S., Wang, A., Jiang, W., and Guan, Z. (2008). Pharmacokinetic Characteristics and Anticancer Effects of 5-fluorouracil Loaded Nanoparticles. BMC Cancer 8, 103. doi:10.1186/1471-2407-8-103

Li, Y., Gao, Y., Gong, C., Wang, Z., Xia, Q., Gu, F., et al. (2018). A33 Antibody-Functionalized Exosomes for Targeted Delivery of Doxorubicin against Colorectal Cancer. Nanomedicine 14, 1973–1985. doi:10.1016/j.nano.2018.05.020

Liszbinski, R. B., Romagnoli, G. G., Gorgulho, C. M., Basso, C. R., Pedrosa, V. A., and Kaneno, R. (2020). Anti-EGFR-Coated Gold Nanoparticles In Vitro Carry 5-Fluorouracil to Colorectal Cancer Cells. Materials (Basel) 13, 375. doi:10.3390/ma13020375

Liu, F., Li, M., Liu, C., Liu, Y., Liang, Y., Wang, F., et al. (2014). Tumor-specific Delivery and Therapy by Double-Targeted DTX-CMCS-PEG-NGR Conjugates. Pharm. Res. 31, 475–488. doi:10.1007/s11095-013-1176-3

Liu, J., Cui, L., and Losic, D. (2013). Graphene and Graphene Oxide as New Nanocarriers for Drug Delivery Applications. Acta Biomater. 9, 9243–9257. doi:10.1016/j.actbio.2013.08.016

Liu, S. (2012). Epigenetics Advancing Personalized Nanomedicine in Cancer Therapy. Adv. Drug Deliv. Rev. 64, 1532–1543. doi:10.1016/j.addr.2012.08.004

Liu, W., Zhu, Y., Wang, F., Li, X., Liu, X., Pang, J., et al. (2018). Galactosylated Chitosan-Functionalized Mesoporous Silica Nanoparticles for Efficient colon Cancer Cell-Targeted Drug Delivery. R. Soc. Open Sci. 5, 181027. doi:10.1098/rsos.181027

Liu, X. X., Rocchi, P., Qu, F. Q., Zheng, S. Q., Liang, Z. C., Gleave, M., et al. (2009). PAMAM Dendrimers Mediate siRNA Delivery to Target Hsp27 and Produce Potent Antiproliferative Effects on Prostate Cancer Cells. ChemMedChem 4, 1302–1310. doi:10.1002/cmdc.200900076

Lorusso, D., Sabatucci, I., Maltese, G., Lepori, S., Tripodi, E., Bogani, G., et al. (2019). Treatment of Recurrent Ovarian Cancer with Pegylated Liposomal Doxorubicin: a Reappraisal and Critical Analysis. Tumori 105, 282–287. doi:10.1177/0300891619839308

Lu, Z., Qi, L., Lin, Y. R., Sun, L., Zhang, L., Wang, G. C., et al. (2020). Novel Albumin Nanoparticle Enhanced the Anti-insulin-resistant-hepatoma Activity of Metformin. Int. J. Nanomedicine 15, 5203–5215. doi:10.2147/ijn.S253094

Luan, X., Rahme, K., Cong, Z., Wang, L., Zou, Y., He, Y., et al. (2019). Anisamide-targeted PEGylated Gold Nanoparticles Designed to Target Prostate Cancer Mediate: Enhanced Systemic Exposure of siRNA, Tumour Growth Suppression and a Synergistic Therapeutic Response in Combination with Paclitaxel in Mice. Eur. J. Pharm. Biopharm. 137, 56–67. doi:10.1016/j.ejpb.2019.02.013

Luo, M., Lewik, G., Ratcliffe, J. C., Choi, C. H. J., Mäkilä, E., Tong, W. Y., et al. (2019). Systematic Evaluation of Transferrin-Modified Porous Silicon Nanoparticles for Targeted Delivery of Doxorubicin to Glioblastoma. ACS Appl. Mater. Inter. 11, 33637–33649. doi:10.1021/acsami.9b10787

Ma, Y., Li, R., Dong, Y., You, C., Huang, S., Li, X., et al. (2021). tLyP-1 Peptide Functionalized Human H Chain Ferritin for Targeted Delivery of Paclitaxel. Int. J. Nanomedicine 16, 789–802. doi:10.2147/ijn.S289005

Mach, C. M., Mathew, L., Mosley, S. A., Kurzrock, R., and Smith, J. A. (2009). Determination of Minimum Effective Dose and Optimal Dosing Schedule for Liposomal Curcumin in a Xenograft Human Pancreatic Cancer Model. Anticancer Res. 29, 1895–1899.

Mahmoudi, R., Ashraf Mirahmadi-Babaheidri, S., Delaviz, H., Fouani, M. H., Alipour, M., Jafari Barmak, M., et al. (2021). RGD Peptide-Mediated Liposomal Curcumin Targeted Delivery to Breast Cancer Cells. J. Biomater. Appl. 35, 743–753. doi:10.1177/0885328220949367

Malekmohammadi, S., Hadadzadeh, H., Farrokhpour, H., and Amirghofran, Z. (2018). Immobilization of Gold Nanoparticles on Folate-Conjugated Dendritic Mesoporous Silica-Coated Reduced Graphene Oxide Nanosheets: a New Nanoplatform for Curcumin pH-Controlled and Targeted Delivery. Soft Matter 14, 2400–2410. doi:10.1039/c7sm02248d

Mani, G., Kim, S., and Kim, K. (2018). Development of Folate-Thioglycolate-Gold Nanoconjugates by Using Citric Acid-PEG Branched Polymer for Inhibition of MCF-7 Cancer Cell Proliferation. Biomacromolecules 19, 3257–3267. doi:10.1021/acs.biomac.8b00543

Manju, S., and Sreenivasan, K. (2012). Gold Nanoparticles Generated and Stabilized by Water Soluble Curcumin-Polymer Conjugate: Blood Compatibility Evaluation and Targeted Drug Delivery onto Cancer Cells. J. Colloid Interf. Sci. 368, 144–151. doi:10.1016/j.jcis.2011.11.024

Mansoori, B., Mohammadi, A., Abedi-Gaballu, F., Abbaspour, S., Ghasabi, M., Yekta, R., et al. (2020). Hyaluronic Acid-Decorated Liposomal Nanoparticles for Targeted Delivery of 5-fluorouracil into HT-29 Colorectal Cancer Cells. J. Cell Physiol 235, 6817–6830. doi:10.1002/jcp.29576

Marcinkowska, M., Stanczyk, M., Janaszewska, A., Sobierajska, E., Chworos, A., and Klajnert-Maculewicz, B. (2019b). Multicomponent Conjugates of Anticancer Drugs and Monoclonal Antibody with PAMAM Dendrimers to Increase Efficacy of HER-2 Positive Breast Cancer Therapy. Pharm. Res. 36, 154. doi:10.1007/s11095-019-2683-7

Marcinkowska, M., Stanczyk, M., Janaszewska, A., Gajek, A., Ksiezak, M., Dzialak, P., et al. (2019a). Molecular Mechanisms of Antitumor Activity of PAMAM Dendrimer Conjugates with Anticancer Drugs and a Monoclonal Antibody. Polymers 11, 1422. doi:10.3390/polym11091422

Maya, S., Kumar, L. G., Sarmento, B., Sanoj Rejinold, N., Menon, D., Nair, S. V., et al. (2013). Cetuximab Conjugated O-Carboxymethyl Chitosan Nanoparticles for Targeting EGFR Overexpressing Cancer Cells. Carbohydr. Polym. 93, 661–669. doi:10.1016/j.carbpol.2012.12.032

Mendt, M., Kamerkar, S., Sugimoto, H., McAndrews, K. M., Wu, C. C., Gagea, M., et al. (2018). Generation and Testing of Clinical-Grade Exosomes for Pancreatic Cancer. JCI Insight 3, 99263. doi:10.1172/jci.insight.99263

Mitra, A. K., Agrahari, V., Mandal, A., Cholkar, K., Natarajan, C., Shah, S., et al. (2015). Novel Delivery Approaches for Cancer Therapeutics. J. Control Release 219, 248–268. doi:10.1016/j.jconrel.2015.09.067

Mitra, M., Kandalam, M., Rangasamy, J., Shankar, B., Maheswari, U. K., Swaminathan, S., et al. (2013). Novel Epithelial Cell Adhesion Molecule Antibody Conjugated Polyethyleneimine-Capped Gold Nanoparticles for Enhanced and Targeted Small Interfering RNA Delivery to Retinoblastoma Cells. Mol. Vis. 19, 1029–1038.

Moghimipour, E., Rezaei, M., Ramezani, Z., Kouchak, M., Amini, M., Angali, K. A., et al. (2018). Transferrin Targeted Liposomal 5-fluorouracil Induced Apoptosis via Mitochondria Signaling Pathway in Cancer Cells. Life Sci. 194, 104–110. doi:10.1016/j.lfs.2017.12.026

Mohammed, M. A., Syeda, J. T. M., Wasan, K. M., and Wasan, E. K. (2017). An Overview of Chitosan Nanoparticles and its Application in Non-parenteral Drug Delivery. Pharmaceutics 9, 53. doi:10.3390/pharmaceutics9040053

Morales, D. R., and Morris, A. D. (2015). Metformin in Cancer Treatment and Prevention. Annu. Rev. Med. 66, 17–29. doi:10.1146/annurev-med-062613-093128

Mousavi, S. M., Hashemi, S. A., Ghasemi, Y., Amani, A. M., Babapoor, A., and Arjmand, O. (2019). Applications of Graphene Oxide in Case of Nanomedicines and Nanocarriers for Biomolecules: Review Study. Drug Metab. Rev. 51, 12–41. doi:10.1080/03602532.2018.1522328

Mukherjee, S., Dasari, M., Priyamvada, S., Kotcherlakota, R., Bollu, V. S., and Patra, C. R. (2015). A green Chemistry Approach for the Synthesis of Gold Nanoconjugates that Induce the Inhibition of Cancer Cell Proliferation through Induction of Oxidative Stress and Their In Vivo Toxicity Study. J. Mater. Chem. B 3, 3820–3830. doi:10.1039/c5tb00244c

Mukherjee, S., B, V., Prashanthi, S., Bangal, P. R., Sreedhar, B., and Patra, C. R. (2013). Potential Therapeutic and Diagnostic Applications of One-step In Situ Biosynthesized Gold Nanoconjugates (2-in-1 System) in Cancer Treatment. RSC Adv. 3, 2318. doi:10.1039/c2ra22299j

Mulens-Arias, V., Nicolás-Boluda, A., Pinto, A., Balfourier, A., Carn, F., Silva, A. K. A., et al. (2021). Tumor-Selective Immune-Active Mild Hyperthermia Associated with Chemotherapy in Colon Peritoneal Metastasis by Photoactivation of Fluorouracil-Gold Nanoparticle Complexes. ACS Nano 15, 3330–3348. doi:10.1021/acsnano.0c10276

Mun, E. J., Babiker, H. M., Weinberg, U., Kirson, E. D., and Von Hoff, D. D. (2018). Tumor-Treating Fields: A Fourth Modality in Cancer Treatment. Clin. Cancer Res. 24, 266–275. doi:10.1158/1078-

Narmani, A., Rezvani, M., Farhood, B., Darkhor, P., Mohammadnejad, J., Amini, B., et al. (2019). Folic Acid Functionalized Nanoparticles as Pharmaceutical Carriers in Drug Delivery Systems. Drug Dev. Res. 80, 404–424. doi:10.1002/ddr.21545

Nasrollahi, F., Varshosaz, J., Khodadadi, A. A., Lim, S., and Jahanian-Najafabadi, A. (2016). Targeted Delivery of Docetaxel by Use of Transferrin/Poly(allylamine Hydrochloride)-Functionalized Graphene Oxide Nanocarrier. ACS Appl. Mater. Inter. 8, 13282–13293. doi:10.1021/acsami.6b02790

Nawaz, A., and Wong, T. W. (2018). Chitosan-Carboxymethyl-5-Fluorouracil-Folate Conjugate Particles: Microwave Modulated Uptake by Skin and Melanoma Cells. J. Invest Dermatol. 138, 2412–2422. doi:10.1016/j.jid.2018.04.037

Ngernyuang, N., Seubwai, W., Daduang, S., Boonsiri, P., Limpaiboon, T., and Daduang, J. (2016). Targeted Delivery of 5-fluorouracil to Cholangiocarcinoma Cells Using Folic Acid as a Targeting Agent. Mater. Sci. Eng. C Mater. Biol. Appl. 60, 411–415. doi:10.1016/j.msec.2015.11.062

Nicoletti, M. I., Lucchini, V., D'Incalci, M., and Giavazzi, R. (1994). Comparison of Paclitaxel and Docetaxel Activity on Human Ovarian Carcinoma Xenografts. Eur. J. Cancer 30a, 691–696. doi:10.1016/0959-8049(94)90547-9

Nie, L., Sun, S., Sun, M., Zhou, Q., Zhang, Z., Zheng, L., et al. (2020). Synthesis of Aptamer-PEI-G-PEG Modified Gold Nanoparticles Loaded with Doxorubicin for Targeted Drug Delivery. JoVE, e61139. doi:10.3791/61139

Ovais, M., Khalil, A. T., Ayaz, M., Ahmad, I., Nethi, S. K., and Mukherjee, S. (2018a). Biosynthesis of Metal Nanoparticles via Microbial Enzymes: A Mechanistic Approach. Int. J. Mol. Sci. 19, 100. doi:10.3390/ijms19124100

Ovais, M., Zia, N., Ahmad, I., Khalil, A. T., Raza, A., Ayaz, M., et al. (2018b). Phyto-Therapeutic and Nanomedicinal Approaches to Cure Alzheimer's Disease: Present Status and Future Opportunities. Front Aging Neurosci. 10, 284. doi:10.3389/fnagi.2018.00284

Palombarini, F., Di Fabio, E., Boffi, A., Macone, A., and Bonamore, A. (2020). Ferritin Nanocages for Protein Delivery to Tumor Cells. Molecules 25, 825. doi:10.3390/molecules25040825

Pan, G., Jia, T. T., Huang, Q. X., Qiu, Y. Y., Xu, J., Yin, P. H., et al. (2017). Mesoporous Silica Nanoparticles (MSNs)-Based Organic/inorganic Hybrid Nanocarriers Loading 5-Fluorouracil for the Treatment of colon Cancer with Improved Anticancer Efficacy. Colloids Surf. B. Biointerfaces 159, 375–385. doi:10.1016/j.colsurfb.2017.08.013

Pan, Y., Leifert, A., Ruau, D., Neuss, S., Bornemann, J., Schmid, G., et al. (2009). Gold Nanoparticles of Diameter 1.4 Nm Trigger Necrosis by Oxidative Stress and Mitochondrial Damage. Small 5, 2067–2076. doi:10.1002/smll.200900466

Patra, S., Mukherjee, S., Barui, A. K., Ganguly, A., Sreedhar, B., and Patra, C. R. (2015). Green Synthesis, Characterization of Gold and Silver Nanoparticles and Their Potential Application for Cancer Therapeutics. Mater. Sci. Eng. C Mater. Biol. Appl. 53, 298–309. doi:10.1016/j.msec.2015.04.048

Pazdur, R., Kudelka, A. P., Kavanagh, J. J., Cohen, P. R., and Raber, M. N. (1993). The Taxoids: Paclitaxel (Taxol) and Docetaxel (Taxotere). Cancer Treat Rev. 19, 351–386. doi:10.1016/0305-7372(93)90010-o

Pecot, C. V., Wu, S. Y., Bellister, S., Filant, J., Rupaimoole, R., Hisamatsu, T., et al. (2014). Therapeutic Silencing of KRAS Using Systemically Delivered siRNAs. Mol. Cancer Ther. 13, 2876–2885. doi:10.1158/1535-7163.Mct-14-0074

Pędziwiatr-Werbicka, E., Gorzkiewicz, M., Horodecka, K., Abashkin, V., Klajnert-Maculewicz, B., Peña-González, C. E., et al. (2020). Silver Nanoparticles Surface-Modified with Carbosilane Dendrons as Carriers of Anticancer siRNA. Int. J. Mol. Sci. 21, 4647. doi:10.3390/ijms21134647

Petrilli, R., Eloy, J. O., Saggioro, F. P., Chesca, D. L., de Souza, M. C., Dias, M. V. S., et al. (2018). Skin Cancer Treatment Effectiveness Is Improved by Iontophoresis of EGFR-Targeted Liposomes Containing 5-FU Compared with Subcutaneous Injection. J. Control Release 283, 151–162. doi:10.1016/j.jconrel.2018.05.038

Podhorecka, M., Ibanez, B., and Dmoszyńska, A. (2017). Metformin - its Potential Anti-cancer and Anti-aging Effects. Postepy Hig Med. Dosw (Online) 71, 170–175. doi:10.5604/01.3001.0010.3801

Prabaharan, M. (2015). Chitosan-based Nanoparticles for Tumor-Targeted Drug Delivery. Int. J. Biol. Macromol 72, 1313–1322. doi:10.1016/j.ijbiomac.2014.10.052

Qu, M. H., Zeng, R. F., Fang, S., Dai, Q. S., Li, H. P., and Long, J. T. (2014). Liposome-based Co-delivery of siRNA and Docetaxel for the Synergistic Treatment of Lung Cancer. Int. J. Pharm. 474, 112–122. doi:10.1016/j.ijpharm.2014.08.019

Qu, Y., Sun, F., He, F., Yu, C., Lv, J., Zhang, Q., et al. (2019). Glycyrrhetinic Acid-Modified Graphene Oxide Mediated siRNA Delivery for Enhanced Liver-Cancer Targeting Therapy. Eur. J. Pharm. Sci. 139, 105036. doi:10.1016/j.ejps.2019.105036

Rahimi-Moghaddam, F., Sattarahmady, N., and Azarpira, N, (2019). Gold-Curcumin Nanostructure in Photo-thermal Therapy on Breast Cancer Cell Line: 650 and 808 Nm Diode Lasers as Light Sources. J. Biomed. Phys. Eng. 9, 473–482. doi:10.31661/jbpe.v0i0.906

Rahnama, E., Mahmoodian-Moghaddam, M., Khorsand-Ahmadi, S., Saberi, M. R., and Chamani, J. (2015). Binding Site Identification of Metformin to Human Serum Albumin and Glycated Human Serum Albumin by Spectroscopic and Molecular Modeling Techniques: a Comparison Study. J. Biomol. Struct. Dyn. 33, 513–533. doi:10.1080/07391102.2014.893540

Rakhit, C. P., Trigg, R. M., Le Quesne, J., Kelly, M., Shaw, J. A., Pritchard, C., et al. (2019). Early Detection of Pre-malignant Lesions in a KRASG12D-Driven Mouse Lung Cancer Model by Monitoring Circulating Free DNA. Dis. Model Mech. 12, dmm036863. doi:10.1242/dmm.036863

Ranjan, A. P., Mukerjee, A., Helson, L., Gupta, R., and Vishwanatha, J. K. (2013). Efficacy of Liposomal Curcumin in a Human Pancreatic Tumor Xenograft Model: Inhibition of Tumor Growth and Angiogenesis. Anticancer Res. 33, 3603–3609.

Rao, D. D., Vorhies, J. S., Senzer, N., and Nemunaitis, J. (2009). siRNA vs. shRNA: Similarities and Differences. Adv. Drug Deliv. Rev. 61, 746–759. doi:10.1016/j.addr.2009.04.004

Rao, P. V., Nallappan, D., Madhavi, K., Rahman, S., Jun Wei, L., and Gan, S. H. (2016). Phytochemicals and Biogenic Metallic Nanoparticles as Anticancer Agents. Oxid Med. Cell Longev 2016, 3685671. doi:10.1155/2016/3685671

Riaz, M. K., Riaz, M. A., Zhang, X., Lin, C., Wong, K. H., Chen, X., et al. (2018). Surface Functionalization and Targeting Strategies of Liposomes in Solid Tumor Therapy: A Review. Int. J. Mol. Sci. 19, 195. doi:10.3390/ijms19010195

Rivankar, S. (2014). An Overview of Doxorubicin Formulations in Cancer Therapy. J. Cancer Res. Ther. 10, 853–858. doi:10.4103/0973-1482.139267

Sahu, S. K., Maiti, S., Maiti, T. K., Ghosh, S. K., and Pramanik, P. (2011). Hydrophobically Modified Carboxymethyl Chitosan Nanoparticles Targeted Delivery of Paclitaxel. J. Drug Target 19, 104–113. doi:10.3109/10611861003733987

Saini, N., and Yang, X. (2018). Metformin as an Anti-cancer Agent: Actions and Mechanisms Targeting Cancer Stem Cells. Acta Biochim. Biophys. Sin (Shanghai) 50, 133–143. doi:10.1093/abbs/gmx106

Schwendener, R. A. (2007). Liposomes in Biology and Medicine. Adv. Exp. Med. Biol. 620, 117–128. doi:10.1007/978-0-387-76713-0_9

Shariatinia, Z. (2018). Carboxymethyl Chitosan: Properties and Biomedical Applications. Int. J. Biol. Macromol 120, 1406–1419. doi:10.1016/j.ijbiomac.2018.09.131

Sharma, A., Goyal, A. K., and Rath, G. (2018). Recent Advances in Metal Nanoparticles in Cancer Therapy. J. Drug Target 26, 617–632. doi:10.1080/1061186x.2017.1400553

Shen, J.-M., Tang, W.-J., Zhang, X.-L., Chen, T., and Zhang, H.-X. (2012). A Novel Carboxymethyl Chitosan-Based folate/Fe3O4/CdTe Nanoparticle for Targeted Drug Delivery and Cell Imaging. Carbohydr. Polym. 88, 239–249. doi:10.1016/j.carbpol.2011.11.087

Shi, H. S., Gao, X., Li, D., Zhang, Q. W., Wang, Y. S., Zheng, Y., et al. (2012a). A Systemic Administration of Liposomal Curcumin Inhibits Radiation Pneumonitis and Sensitizes Lung Carcinoma to Radiation. Int. J. Nanomedicine 7, 2601–2611. doi:10.2147/ijn.S31439

Shi, K., Zhao, Y., Miao, L., Satterlee, A., Haynes, M., Luo, C., et al. (2017). Dual Functional LipoMET Mediates Envelope-type Nanoparticles to Combinational Oncogene Silencing and Tumor Growth Inhibition. Mol. Ther. 25, 1567–1579. doi:10.1016/j.ymthe.2017.02.008

Shi, L., Tang, C., and Yin, C. (2012b). Glycyrrhizin-modified O-Carboxymethyl Chitosan Nanoparticles as Drug Vehicles Targeting Hepatocellular Carcinoma. Biomaterials 33, 7594–7604. doi:10.1016/j.biomaterials.2012.06.072

Shi, X., Du, Y., Yang, J., Zhang, B., and Sun, L. (2006). Effect of Degree of Substitution and Molecular Weight of Carboxymethyl Chitosan Nanoparticles on Doxorubicin Delivery. J. Appl. Polym. Sci. 100, 4689–4696. doi:10.1002/app.23040

Shukla, S. K., Kulkarni, N. S., Chan, A., Parvathaneni, V., Farrales, P., Muth, A., et al. (2019). Metformin-Encapsulated Liposome Delivery System: An Effective Treatment Approach against Breast Cancer. Pharmaceutics 11, 559. doi:10.3390/pharmaceutics11110559

Singh, A., Trivedi, P., and Jain, N. K. (2018a). Advances in siRNA Delivery in Cancer Therapy. Artif. Cells Nanomed Biotechnol 46, 274–283. doi:10.1080/21691401.2017.1307210

Singh, D. P., Herrera, C. E., Singh, B., Singh, S., Singh, R. K., and Kumar, R. (2018b). Graphene Oxide: An Efficient Material and Recent Approach for Biotechnological and Biomedical Applications. Mater. Sci. Eng. C Mater. Biol. Appl. 86, 173–197. doi:10.1016/j.msec.2018.01.004

Singh, P., Gupta, U., Asthana, A., and Jain, N. K. (2008). Folate and Folate-PEG-PAMAM Dendrimers: Synthesis, Characterization, and Targeted Anticancer Drug Delivery Potential in Tumor Bearing Mice. Bioconjug. Chem. 19, 2239–2252. doi:10.1021/bc800125u

Slingerland, M., Guchelaar, H. J., and Gelderblom, H. (2012). Liposomal Drug Formulations in Cancer Therapy: 15 Years along the Road. Drug Discov. Todaytoday 17, 160–166. doi:10.1016/j.drudis.2011.09.015

Snima, K. S., Jayakumar, R., and Lakshmanan, V. K. (2014). In Vitro and In Vivo Biological Evaluation of O-Carboxymethyl Chitosan Encapsulated Metformin Nanoparticles for Pancreatic Cancer Therapy. Pharm. Res. 31, 3361–3370. doi:10.1007/s11095-014-1425-0

Snima, K. S., Jayakumar, R., Unnikrishnan, A. G., Nair, S. V., and Lakshmanan, V. K. (2012). O-carboxymethyl Chitosan Nanoparticles for Metformin Delivery to Pancreatic Cancer Cells. Carbohydr. Polym. 89, 1003–1007. doi:10.1016/j.carbpol.2012.04.050

Su, C., Li, H., Shi, Y., Wang, G., Liu, L., Zhao, L., et al. (2014a). Carboxymethyl-β-cyclodextrin Conjugated Nanoparticles Facilitate Therapy for Folate Receptor-Positive Tumor with the Mediation of Folic Acid. Int. J. Pharm. 474, 202–211. doi:10.1016/j.ijpharm.2014.08.026

Su, Z., Xing, L., Chen, Y., Xu, Y., Yang, F., Zhang, C., et al. (2014b). Lactoferrin-modified Poly(ethylene Glycol)-Grafted BSA Nanoparticles as a Dual-Targeting Carrier for Treating Brain Gliomas. Mol. Pharm. 11, 1823–1834. doi:10.1021/mp500238m

Sun, T., Zhang, Y. S., Pang, B., Hyun, D. C., Yang, M., and Xia, Y. (2014). Engineered Nanoparticles for Drug Delivery in Cancer Therapy. Angew. Chem. Int. Ed. Engl. 53, 12320–12364. doi:10.1002/anie.201403036

Sun, X., Chen, Y., Zhao, H., Qiao, G., Liu, M., Zhang, C., et al. (2018). Dual-modified Cationic Liposomes Loaded with Paclitaxel and Survivin siRNA for Targeted Imaging and Therapy of Cancer Stem Cells in Brain Glioma. Drug Deliv. 25, 1718–1727. doi:10.1080/10717544.2018.1494225

Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., et al. (2021). Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 71, 209–249. doi:10.3322/caac.21660

Tamarov, K. P., Osminkina, L. A., Zinovyev, S. V., Maximova, K. A., Kargina, J. V., Gongalsky, M. B., et al. (2014). Radio Frequency Radiation-Induced Hyperthermia Using Si Nanoparticle-Based Sensitizers for Mild Cancer Therapy. Sci. Rep. 4, 7034. doi:10.1038/srep07034

Tang, Y., Liu, Y., Xie, Y., Chen, J., and Dou, Y. (2020). Apoptosis of A549 Cells by Small Interfering RNA Targeting Survivin Delivery Using Poly-β-Amino Ester/guanidinylated O-Carboxymethyl Chitosan Nanoparticles. Asian J. Pharm. Sci. 15, 121–128. doi:10.1016/j.ajps.2018.09.009

Tao, H., Xu, H., Zuo, L., Li, C., Qiao, G., Guo, M., et al. (2020). Exosomes-coated Bcl-2 siRNA Inhibits the Growth of Digestive System Tumors Both In Vitro and In Vivo. Int. J. Biol. Macromol 161, 470–480. doi:10.1016/j.ijbiomac.2020.06.052

Taverna, S., Fontana, S., Monteleone, F., Pucci, M., Saieva, L., De Caro, V., et al. (2016). Curcumin Modulates Chronic Myelogenous Leukemia Exosomes Composition and Affects Angiogenic Phenotype via Exosomal miR-21. Oncotarget 7, 30420–30439. doi:10.18632/oncotarget.8483

Thakkar, K. N., Mhatre, S. S., and Parikh, R. Y. (2010). Biological Synthesis of Metallic Nanoparticles. Nanomedicine 6, 257–262. doi:10.1016/j.nano.2009.07.002

Theek, B., Rizzo, L. Y., Ehling, J., Kiessling, F., and Lammers, T. (2014). The Theranostic Path to Personalized Nanomedicine. Clin. Transl Imaging 2, 66–76. doi:10.1007/s40336-014-0051-5

Théry, C., Zitvogel, L., and Amigorena, S. (2002). Exosomes: Composition, Biogenesis and Function. Nat. Rev. Immunol. 2, 569–579. doi:10.1038/nri855

Thomas, T. J., Tajmir-Riahi, H. A., and Pillai, C. K. S. (2019). Biodegradable Polymers for Gene Delivery. Molecules 24, 3744. doi:10.3390/molecules24203744

Tian, L., Wang, S., Jiang, S., Liu, Z., Wan, X., Yang, C., et al. (2021). Luteolin as an Adjuvant Effectively Enhances CTL Anti-tumor Response in B16F10 Mouse Model. Int. Immunopharmacol. 94, 107441. doi:10.1016/j.intimp.2021.107441

Tolstik, E., Osminkina, L. A., Matthäus, C., Burkhardt, M., Tsurikov, K. E., Natashina, U. A., et al. (2016). Studies of Silicon Nanoparticles Uptake and Biodegradation in Cancer Cells by Raman Spectroscopy. Nanomedicine 12, 1931–1940. doi:10.1016/j.nano.2016.04.004

Tomalia, D. A. (2012). Interview: An Architectural Journey: from Trees, Dendrons/dendrimers to Nanomedicine. Interview by Hannah Stanwix. Nanomedicine (Lond) 7, 953–956. doi:10.2217/nnm.12.81

Tong, W. Y., Alnakhli, M., Bhardwaj, R., Apostolou, S., Sinha, S., Fraser, C., et al. (2018). Delivery of siRNA In Vitro and In Vivo Using PEI-Capped Porous Silicon Nanoparticles to Silence MRP1 and Inhibit Proliferation in Glioblastoma. J. Nanobiotechnology 16, 38. doi:10.1186/s12951-018-0365-y

Truffi, M., Fiandra, L., Sorrentino, L., Monieri, M., Corsi, F., and Mazzucchelli, S. (2016). Ferritin Nanocages: A Biological Platform for Drug Delivery, Imaging and Theranostics in Cancer. Pharmacol. Res. 107, 57–65. doi:10.1016/j.phrs.2016.03.002

Udofot, O., Affram, K., Israel, B., and Agyare, E. (2015). Cytotoxicity of 5-Fluorouracil-Loaded pH-Sensitive Liposomal Nanoparticles in Colorectal Cancer Cell Lines. Integr. Cancer Sci. Ther. 2, 245–252. doi:10.15761/icst.1000150

van den Boorn, J. G., Dassler, J., Coch, C., Schlee, M., and Hartmann, G. (2013). Exosomes as Nucleic Acid Nanocarriers. Adv. Drug Deliv. Rev. 65, 331–335. doi:10.1016/j.addr.2012.06.011

Wang, C., Ma, Q., Dou, W., Kanwal, S., Wang, G., Yuan, P., et al. (2009). Synthesis of Aqueous CdTe Quantum Dots Embedded Silica Nanoparticles and Their Applications as Fluorescence Probes. Talanta 77, 1358–1364. doi:10.1016/j.talanta.2008.09.018

Wang, J., and Zhang, B. (2018). Bovine Serum Albumin as a Versatile Platform for Cancer Imaging and Therapy. Curr. Med. Chem. 25, 2938–2953. doi:10.2174/0929867324666170314143335

Wang, W. Y., Cao, Y. X., Zhou, X., and Wei, B. (2019). Delivery of Folic Acid-Modified Liposomal Curcumin for Targeted Cervical Carcinoma Therapy. Drug Des. Devel Ther. 13, 2205–2213. doi:10.2147/dddt.S205787

Wang, X. Y., Ishida, T., Ichihara, M., and Kiwada, H. (2005). Influence of the Physicochemical Properties of Liposomes on the Accelerated Blood Clearance Phenomenon in Rats. J. Control Release 104, 91–102. doi:10.1016/j.jconrel.2005.01.008

Wei, Y., Pu, X., and Zhao, L. (2017). Preclinical Studies for the Combination of Paclitaxel and Curcumin in Cancer Therapy (Review). Oncol. Rep. 37, 3159–3166. doi:10.3892/or.2017.5593

Wei, Y., Yang, P., Cao, S., and Zhao, L. (2018). The Combination of Curcumin and 5-fluorouracil in Cancer Therapy. Arch. Pharm. Res. 41, 1–13. doi:10.1007/s12272-017-0979-x

Wicki, A., Witzigmann, D., Balasubramanian, V., and Huwyler, J. (2015). Nanomedicine in Cancer Therapy: Challenges, Opportunities, and Clinical Applications. J. Control Release 200, 138–157. doi:10.1016/j.jconrel.2014.12.030

Wu, H., Zhou, J., Zeng, C., Wu, D., Mu, Z., Chen, B., et al. (2016). Curcumin Increases Exosomal TCF21 Thus Suppressing Exosome-Induced Lung Cancer. Oncotarget 7, 87081–87090. doi:10.18632/oncotarget.13499

Wu, S. Y., An, S. S., and Hulme, J. (2015). Current Applications of Graphene Oxide in Nanomedicine. Int. J. Nanomedicine 10 (Spec Iss), 9–24. doi:10.2147/ijn.S88285

Xia, B., Zhang, Q., Shi, J., Li, J., Chen, Z., and Wang, B. (2018). Co-loading of Photothermal Agents and Anticancer Drugs into Porous Silicon Nanoparticles with Enhanced Chemo-Photothermal Therapeutic Efficacy to Kill Multidrug-Resistant Cancer Cells. Colloids Surf. B. Biointerfaces 164, 291–298. doi:10.1016/j.colsurfb.2018.01.059

Xiao, B., Ma, L., and Merlin, D. (2017). Nanoparticle-mediated Co-delivery of Chemotherapeutic Agent and siRNA for Combination Cancer Therapy. Expert Opin. Drug Deliv. 14, 65–73. doi:10.1080/17425247.2016.1205583

Xie, Y., Qiao, H., Su, Z., Chen, M., Ping, Q., and Sun, M. (2014). PEGylated Carboxymethyl Chitosan/calcium Phosphate Hybrid Anionic Nanoparticles Mediated hTERT siRNA Delivery for Anticancer Therapy. Biomaterials 35, 7978–7991. doi:10.1016/j.biomaterials.2014.05.068

Xiong, W., Qi, L., Jiang, N., Zhao, Q., Chen, L., Jiang, X., et al. (2021). Metformin Liposome-Mediated PD-L1 Downregulation for Amplifying the Photodynamic Immunotherapy Efficacy. ACS Appl. Mater. Inter. 13, 8026–8041. doi:10.1021/acsami.0c21743

Xu, W. W., Liu, D. Y., Cao, Y. C., and Wang, X. Y. (2017). GE11 Peptide-Conjugated Nanoliposomes to Enhance the Combinational Therapeutic Efficacy of Docetaxel and siRNA in Laryngeal Cancers. Int. J. Nanomedicine 12, 6461–6470. doi:10.2147/ijn.S129946

Yan, L., Gao, S., Shui, S., Liu, S., Qu, H., Liu, C., et al. (2020). Small Interfering RNA-Loaded Chitosan Hydrochloride/carboxymethyl Chitosan Nanoparticles for Ultrasound-Triggered Release to Hamper Colorectal Cancer Growth In Vitro. Int. J. Biol. Macromol 162, 1303–1310. doi:10.1016/j.ijbiomac.2020.06.246

Yang, Y., Xie, X., Xu, X., Xia, X., Wang, H., Li, L., et al. (2016). Thermal and Magnetic Dual-Responsive Liposomes with a Cell-Penetrating Peptide-siRNA Conjugate for Enhanced and Targeted Cancer Therapy. Colloids Surf. B. Biointerfaces 146, 607–615. doi:10.1016/j.colsurfb.2016.07.002

Yang, Z., Wang, J., Liu, S., Li, X., Miao, L., Yang, B., et al. (2020). Defeating Relapsed and Refractory Malignancies through a Nano-Enabled Mitochondria-Mediated Respiratory Inhibition and Damage Pathway. Biomaterials 229, 119580. doi:10.1016/j.biomaterials.2019.119580

Yang, Z. Z., Li, J. Q., Wang, Z. Z., Dong, D. W., and Qi, X. R. (2014). Tumor-targeting Dual Peptides-Modified Cationic Liposomes for Delivery of siRNA and Docetaxel to Gliomas. Biomaterials 35, 5226–5239. doi:10.1016/j.biomaterials.2014.03.017

Yardley, D. A. (2013). Nab-Paclitaxel Mechanisms of Action and Delivery. J. Control Release 170, 365–372. doi:10.1016/j.jconrel.2013.05.041

Ying, H., Dey, P., Yao, W., Kimmelman, A. C., Draetta, G. F., Maitra, A., et al. (2016). Genetics and Biology of Pancreatic Ductal Adenocarcinoma. Genes Dev. 30, 355–385. doi:10.1101/gad.275776.115

Yong, T., Zhang, X., Bie, N., Zhang, H., Zhang, X., Li, F., et al. (2019). Tumor Exosome-Based Nanoparticles Are Efficient Drug Carriers for Chemotherapy. Nat. Commun. 10, 3838. doi:10.1038/s41467-019-11718-4

Yue, J., Feliciano, T. J., Li, W., Lee, A., and Odom, T. W. (2017). Gold Nanoparticle Size and Shape Effects on Cellular Uptake and Intracellular Distribution of siRNA Nanoconstructs. Bioconjug. Chem. 28, 1791–1800. doi:10.1021/acs.bioconjchem.7b00252

Zhang, H. G., Kim, H., Liu, C., Yu, S., Wang, J., Grizzle, W. E., et al. (2007). Curcumin Reverses Breast Tumor Exosomes Mediated Immune Suppression of NK Cell Tumor Cytotoxicity. Biochim. Biophys. Acta 1773, 1116–1123. doi:10.1016/j.bbamcr.2007.04.015

Zhang, M., Zhu, J., Zheng, Y., Guo, R., Wang, S., Mignani, S., et al. (2018). Doxorubicin-Conjugated PAMAM Dendrimers for pH-Responsive Drug Release and Folic Acid-Targeted Cancer Therapy. Pharmaceutics 10, 162. doi:10.3390/pharmaceutics10030162

Zhou, F., Zheng, T., Abdel-Halim, E. S., Jiang, L., and Zhu, J. J. (2016). A Multifunctional Core-Shell Nanoplatform for Enhanced Cancer Cell Apoptosis and Targeted Chemotherapy. J. Mater. Chem. B 4, 2887–2894. doi:10.1039/c6tb00438e

Zhou, L., Jing, Y., Liu, Y., Liu, Z., Gao, D., Chen, H., et al. (2018). Mesoporous Carbon Nanospheres as a Multifunctional Carrier for Cancer Theranostics. Theranostics 8, 663–675. doi:10.7150/thno.21927

Zhu, L., and Chen, L. (2019). Progress in Research on Paclitaxel and Tumor Immunotherapy. Cell. Mol. Biol. Lett. 24, 40. doi:10.1186/s11658-019-0164-y