Abstract: The application prospect of chemotherapy is currently limited by the disadvantages of tumor multidrug resistance (MDR), non-specific drug distribution and systemic toxic side effects. Therapeutic genes can be transported to tumor cells by appropriate vectors to achieve therapeutic purposes by down-regulating the expression of resistance-associated proteins or silencing other genes that regulate tumor function. Therefore, the combination of chemotherapy and gene therapy with the help of nanocarriers can exert the synergistic effect of the two and improve the effect of chemotherapy, which is a promising anticancer strategy. Silencing drug resistance-related genes is the main idea to solve tumor MDR, and it is still necessary to explore other gene therapy strategies that can synergize with chemotherapy to achieve the purpose of cancer treatment for a wider range of targets by regulating one or some links in tumor development. In the meantime, the use of nanoparticles (NPs) to co-deliver genes and chemotherapeutic agents places higher demands on nanocarriers. Genes are easily degraded by nucleases, unstable in the bloodstream, poor cellular uptake and low transfection efficiency, so safe and efficient co-delivery systems are urgently needed to overcome many obstacles and achieve maximum efficiency of drug co-loading and transport. According to the different therapeutic gene targets selected, the therapeutic strategies of gene-chemotherapy drug co-delivery can be divided into various types such as reversing MDR in tumor cells, promoting tumor cell apoptosis, anti-tumor angiogenesis, chemotherapy synergistic immunotherapy and removing cancer stem cells (CSCs), and the delivered genes include MDR-1 siRNA, Bcl-2 siRNA, p53 DNA, VEGF siRNA, PD-L1 siRNA and miR-205. The ideal nanocarrier for co-delivery should meet the conditions of high safety, good biocompatibility, biodegradability, and high gene transfection rate. Researchers have made full use of the characteristic advantages of various materials to develop different types of co-delivery carriers such as polymer nanoparticles, nanomicelles, liposomes, inorganic nanoparticles, viruses and nucleic acid carriers. In addition, the effect of targeted release of drugs according to the changes in tumor microenvironment or external environment can be realized by stimulating responsive design of carriers, so as to avoid the sudden release of encapsulated drugs, ensure the drug distribution at the tumor site, improve the therapeutic efficiency and reduce the toxic side effects on normal tissues. In this review, the phased research progress of co-delivery of genes and chemotherapeutic drugs by nanocarriers is summarized, the co-delivery strategies and co-delivery carriers of gene-chemotherapeutic drugs are introduced, the characteristics of various types of carriers are analyzed, some problems to be solved in the field of nanocarrier research are considered and their prospects are prospected. The above contents provide a reference for realizing safe and efficient gene-chemical combination therapy.
贾斐, 杜传超, 毛天立, 刘宇, 刘晓光. 纳米载体共递送基因和化疗药物用于肿瘤治疗的研究进展[J]. 材料导报, 2022, 36(17): 20080171-9.
JIA Fei, DU Chuanchao, MAO Tianli, LIU Yu, LIU Xiaoguang. Progress in the Use of Nanocarriers for Co-delivery of Genes and Chemotherapeutic Agents for Cancer Therapy. Materials Reports, 2022, 36(17): 20080171-9.
1 Chen Q, Ke H, Dai Z, et al. Biomaterials, 2015, 73, 214. 2 Jardim G, Lima D, Valença W, et al. Molecules, 2017, 23, 83. 3 Wu Q, Yang Z, Nie Y, et al. Cancer Letters, 2014, 347, 159. 4 Pérez-Herrero E, Fernández-Medarde A. European Journal Pharmaceutics and Biopharmaceutics, 2015, 93, 52. 5 Susa M, Choy E, Yang C, et al. Journal of Biomolecular Screening, 2010, 15, 287. 6 Chow E K, Ho D. Science Translational Medicine, 2013, 5, 216rv4. 7 Zhang X Q, Xu X, Bertrand N, et al. Advanced Drug Delivery Reviews, 2012, 64, 1363. 8 Ramya R, Shruthilaya M, Akila K. International Journal of Nanomedicine, 2012, 2012, 1043. 9 Karageorgis A, Dufort S, Sancey L, et al. Scientific Reports, 2016, 6, 21417. 10 Yoo J W, Irvine D J, Discher D E, et al. Nature Reviews Drug Discovery, 2011, 10, 521. 11 Zhao M, van Straten D, Broekman M L D, et al. Theranostics, 2020, 10, 1355. 12 Thibault M, Lavertu M, Astolfi M, et al. Molecular Biotechnology, 2016, 58, 648. 13 Zhang M, Liu E, Cui Y, et al. Cancer Biology & Medicine, 2017, 14, 212. 14 Ahmed K A, Davis B J, Wilson T M, et al. Frontiers in Oncology, 2012, 2, 172. 15 Rui M, Qu Y, Gao T, et al. International Journal of Nanomedicine, 2017, 12, 217. 16 Baek D, Villen J, Shin C, et al. Nature, 2008, 455, 64. 17 Svoronos A A, Engelman D M, Slack F J. Cancer Research, 2016, 76, 3666. 18 Xue H Y, Liu S, Wong H L. Nanomedicine, 2014, 9, 295. 19 Yi Y, Kim H J, Mi P, et al. Journal of Controlled Release, 2016,244, 247. 20 Li X, Sun A N, Liu Y J, et al. NPG Asia Materials, 2018,10, 238. 21 Cullis P R, Hope M J. Molecular Therapy, 2017, 25, 1467. 22 Leber N, Nuhn L, Zentel R. Macromolecular Bioscience, 2017, 17(10), 1700092. 23 Singh M S, Peer D. Therapeutic Delivery, 2016, 7, 51. 24 Shah S, Lal H A. Therapeutic Delivery, 2015, 6, 1131. 25 Abbasi M, Lavasanifar A, Uludag H. Medicinal Research Reviews, 2013, 33, 33. 26 Wu M, Lin X, Tan X, et al. ACS Applied Materials & Interfaces, 2018, 10, 19416. 27 Zhang Q, Kuang G, He S, et al. Nano Letters, 2020, 20, 3039. 28 Hao F, Lee RJ, Yang C, et al. Pharmaceutics, 2019, 11, 92. 29 Xiong X B, Lavasanifar A. ACS Nano, 2011, 5, 5202. 30 Sun T M, Du J Z, Yao Y D, et al. ACS Nano, 2011, 5, 1483. 31 Hussain M, Beale G, Hughes M, et al. International Journal of Pharmaceutics, 2002, 234, 129. 32 Wan W J, Qu C X, Zhou Y J, et al. International Journal of Pharmaceutics, 2019, 566, 731. 33 Zhu Q L, Zhou Y, Guan M, et al. Biomaterials, 2014, 35, 5965. 34 Xu F, Ye M L, Zhang Y P, et al. Cancer Science, 2020, 111, 1528. 35 Xu X, Xie K, Zhang X Q, et al. Proceedings of the National Academy of Sciences, 2013, 110, 18638. 36 Zhang X, Zeng X, Liang X, et al. Biomaterials, 2014, 35, 9144. 37 Cho K, Wang X, Nie S, et al. Clinical Cancer Research, 2008, 14, 1310. 38 Wang D, Xu X, Zhang K, et al. International Journal of Nanomedicine, 2017, 13, 187. 39 Cao Y, Huang H Y, Chen L Q, et al. ACS Applied Materials & Interfaces, 2019, 11, 9763. 40 Zhang X, Pan J, Yao M, et al. European Journal Pharmaceutics and Biopharmaceutics, 2020, 154, 43. 41 Roberts C M, Shahin S A, Wen W, et al. Nanomedicine, 2017, 13, 965. 42 Chen Y, Sun L, Guo D, et al. Journal of Gene Medicine, 2017, 19(12), e2998. 43 Byeon Y, Lee J W, Choi W S, et al. Cancer Research, 2018, 78, 6247. 44 Bahreyni A, Alibolandi M, Ramezani M, et al. Colloids and Surfaces B: Biointerfaces, 2019, 175, 231. 45 Li C, Li T, Huang L, et al. Chemistry-an Asian Journal, 2019, 14, 1570. 46 Wang S, Liu X, Chen S, et al. ACS Nano, 2019, 13, 274. 47 Shen J, Meng Q, Sui H, et al. Molecular Pharmaceutics, 2014, 11, 2579. 48 Li M, Zhao P, Fan T, et al. International Journal of Pharmaceutics, 2019, 572, 118769. 49 Zhang X, Wang Q, Qin L, et al. Drug Delivery, 2016, 23, 2936. 50 Davoodi P, Srinivasan M P, Wang C H. Acta Biomaterialia, 2016, 39, 79. 51 Shi H, Sun S, Xu H, et al. International Journal of Nanomedicine, 2020, 15, 3347. 52 Gong C, Hu C, Gu F, et al. Journal of Controlled Release, 2017, 266, 272. 53 Wang F, Zhang L, Bai X, et al. ACS Applied Materials & Interfaces, 2018, 10, 22767. 54 Kwak G, Jo S D, Kim D, et al. Journal of Controlled Release, 2017, 267, 203. 55 Jang Y, Kim D, Lee H, et al. Nanomedicine, 2020, 27, 102194. 56 Zhou Y J, Wan W J, Tong Y, et al. Journal of Biomedical Materials Research Part B-Applied Biomaterials, 2020, 108, 1710. 57 Song W, Shen L, Wang Y, et al. Nature Communications, 2018, 9, 2237. 58 Tang X, Rao J, Yin S, et al. European Journal of Pharmaceutical Sciences, 2019, 127, 161. 59 Yang T, Chen Y, Zhao P, et al. Nanomedicine, 2018, 14, 2009. 60 Chaudhary A K, Mondal G, Kumar V, et al. Cancer Letters, 2017, 402, 1. 61 Wei J, Han X S, Zhang C W, et al. Materials Reports A: Review Papers, 2019, 33(1), 16(in Chinese). 韦晶,韩希恩,张承武,等.材料导报:综述篇, 2019, 33(1), 16. 62 Akkapeddi P, Azizi S A, Freedy, A M, et al. Chemical Science, 2016, 7, 2954. 63 Hu X, Li J, Lin W, et al. RSC Advances, 2014, 4, 38405. 64 Zhang Y, Xiao C, Li M, et al. Macromolecular Bioscience, 2013, 13, 584. 65 Li W, Wei H, Li H, et al. Nanomedicine (London), 2014, 9, 2587. 66 Miao L, Lin C M, Huang L. Journal of Controlled Release, 2015, 219, 192. 67 Zhu X, Sun Y, Chen D, et al. Journal of Controlled Release, 2017, 254, 107. 68 Ryu J H, Chacko R T, Jiwpanich S, et al. Journal of the American Chemi-cal Society, 2010, 132, 17227. 69 Gao G H, Park M J, Li Y, et al. Biomaterials, 2012, 33, 9157. 70 Li H, Sun Y, Chen D, et al. Scientific Reports, 2015, 5, 15712. 71 Markman J L, Rekechenetshiy A, Holler E, et al. Advanced Drug Delive-ry Reviews, 2013, 65, 1866. 72 Zhang L, Wang T, Li L, et al. Chemical Communication, 2012, 48, 8706. 73 Liu P F, Yu H, Sun Y, et al. Biomaterials, 2012, 33, 4403. 74 Nehate C, Moothedathu Raynold A A, Koul V. ACS Applied Materials & Interfaces, 2017, 9, 39672. 75 Sadreddini S, Safaralizadeh R, Baradaran B, et al. Immunology Letters, 2017, 181, 79. 76 Glasgow M D, Chougule M B. Journal of Biomedical Nanotechnology, 2015, 11, 1859. 77 Pan J, Mendes L P, Yao M, et al. European Journal Pharmaceutics and Biopharmaceutics, 2019, 136, 18. 78 Patil M L, Zhang M, Taratula O, et al. Biomacromolecules, 2009, 10, 258. 79 Zhen X, Cheng P, Pu K. Small, 2019, 15, 1804105. 80 Chen M, Chen M, He J. Artificial Cells Nanomedicine and Biotechnology, 2019, 47, 1635. 81 Cabral H, Kataoka K. Journal of Controlled Release, 2014, 190, 465. 82 Li X, Yu Y, Ji Q, et al. Nanomedicine, 2015, 11, 175. 83 Basak R, Bandyopadhyay R. Langmuir, 2013, 29, 4350. 84 Pitto-Barry A, Barry N P. Polymer Chemistry, 2014, 5, 3291. 85 Zhang C G, Yang S D, Zhu W J, et al. Journal of Biomedical Materials Research Part B-Applied Biomaterials, 2017, 105, 2093. 86 Butt A M, Amin M C, Katas H, et al. Molecular Pharmaceutics, 2016, 13, 4179. 87 Khare R, Li J, Lu Z. Journal of Biomedical Informatics, 2014, 52, 448. 88 Bangham A D, Standish M M, Watkins J C. Journal of Molecular Biology, 1965, 13, 238. 89 Zhang J, Du Z, Pan S, et al. ACS Applied Materials & Interfaces, 2018, 10, 21590. 90 Haghiralsadat F, Amoabediny G, Naderinezhad S, et al. International Journal of Nanomedicine, 2018, 13, 3853. 91 Pang J, Luan Y, Yang X, et al. Mini-reviews in Medicinal Chemistry, 2012, 12, 775. 92 Yu C, Qian L, Ge J, et al. Angewandte Chemie International Edition, 2016, 55, 9272. 93 Yu C, Qian L, Uttamchandani M, et al. Angewandte Chemie International Edition, 2015, 54, 10574. 94 Gupta B, Ruttala H B, Poudel B K, et al. ACS Applied Materials & Interfaces, 2018, 10, 24392. 95 Zhu S H, Huang B Y, Zhou K C. Journal of Nanoparticle Research, 2004, 6, 307. 96 Chen H, Ma X, Li Z, et al. Biomedicine & Pharmacotherapy, 2012, 66, 334. 97 Li J M, Zhao M X, Su H, et al. Biomaterials, 2011, 32, 978. 98 Xiao Y, Jaskula-Sztul R, Javadi A, et al. Nanoscale, 2012, 4, 7185. 99 Yin P T, Pongkulapa T, Cho H Y, et al. ACS Applied Materials & Interfaces, 2018, 10, 26954. 100 Pereira S, Lee J, Rubio N, et al. Pharmaceutical Research, 2015, 32, 3293. 101 Li J M, Wang Y Y, Zhao M X, et al. Biomaterials, 2012, 33, 2780. 102 Yin F, Yang C, Wang Q, et al. Theranostics, 2015, 5, 818. 103 Yang J, Zhang Q, Liu Y, et al. Nanomedicine (London), 2020, 15, 1391. 104 Shen L H, Zhou J, Wang Y X, et al. Small, 2015, 11, 1190. 105 Zhao J, Ye Z, Yang J, et al. Biomaterials, 2020, 240, 119849. 106 Zhou J, Shum K T, Burnett J C, et al. Pharmaceuticals (Basel), 2013, 6, 85. 107 Shu D, Shu Y, Haque F, et al. Nature Nanotechnology, 2011, 6, 658. 108 Cui D, Zhang C, Liu B, et al. Scientific Reports, 2015, 5, 10726. 109 Zahid M, Kim B, Hussain R, et al. Nanoscale Research Letters, 2013, 8, 119. 110 Shu Y, Yin H, Rajabi M, et al. Journal of Controlled Release, 2018, 276, 17. 111 Zhu L, Guo Y, Qian Q, et al. Angewandte Chemie International Edition, 2020, 59(41), 17944. 112 Li W, Huang L, Ying X, et al. Angewandte Chemie International Edition, 2015, 54, 3126. 113 Wu L, Zou Y, Deng C, et al. Biomaterials, 2013, 34, 5262. 114 Lv S, Tang Z, Zhang D, et al. Journal of Controlled Release, 2014, 194, 220. 115 Wan W J, Qu C X, Zhou Y J, et al. International Journal of Pharmaceutics, 2019, 566, 731. 116 Gao Y, Jia L, Wang Q, et al. ACS Applied Materials & Interfaces, 2019, 11, 16296. 117 Tang S, Meng Q, Sun H, et al. Advanced Functional Materials, 2016, 26, 6033. 118 Wu M, Lin X, Tan X, et al. ACS Applied Materials & Interfaces, 2018, 10, 19416. 119 Zhang Q, Kuang G, He S, et al. Nano Letters, 2020, 20, 3039.