专题:纳米生物医学

纳米技术在抗肿瘤药物靶向递释系统中的应用研究进展

  • 于海军 ,
  • 王当歌 ,
  • 杨祥良 ,
  • 李亚平
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  • 1. 中国科学院上海药物研究所, 上海 201203;
    2. 华中科技大学生命科学与技术学院, 武汉 430074
于海军,研究员,研究方向为纳米载药系统和纳米药物,电子信箱:hjyu@simm.ac.cn

收稿日期: 2018-09-12

  修回日期: 2018-11-05

  网络出版日期: 2018-12-14

基金资助

国家自然科学基金项目(31671024,31622025,81521005)

Progress of nanosized drug delivery systems for targeted tumor therapy

  • YU Haijun ,
  • WANG Dangge ,
  • YANG Xiangliang ,
  • LI Yaping
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  • 1. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;
    2. College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China

Received date: 2018-09-12

  Revised date: 2018-11-05

  Online published: 2018-12-14

摘要

纳米载药技术已经在抗肿瘤药物递送领域受到广泛关注。纳米技术可以显著增加难溶性药物的生物利用度,改善药物释放与摄取行为,提高药物对肿瘤组织的靶向性,增加药物在肿瘤组织的分布与蓄积,降低药物对正常组织和细胞毒副作用,实现减毒增效。尽管如此,如何有效克服肿瘤生理屏障,进一步提高化疗药物的肿瘤特异性,实现肿瘤组织深度渗透和肿瘤细胞内可控释药仍然是开发抗肿瘤纳米药物亟需解决的重大挑战。从被动靶向、物理靶向、主动靶向和仿生靶向4个方面概述了纳米载药系统抗肿瘤药物在克服肿瘤屏障实现肿瘤靶向药物递送方面的研究进展。

本文引用格式

于海军 , 王当歌 , 杨祥良 , 李亚平 . 纳米技术在抗肿瘤药物靶向递释系统中的应用研究进展[J]. 科技导报, 2018 , 36(22) : 108 -117 . DOI: 10.3981/j.issn.1000-7857.2018.22.009

Abstract

Nanosized drug delivery systems (NDDS) have shown enormous potential in cancer therapy, as they can increase the bioavailability of poor water-soluble drugs, improve the drug distribution in tumor tissues, promote intracellular uptake as well as drug release inside tumor cells. The rational design of NDDS by utilizing the physiological properties of tumor may suppress the non-specific interactions between NDDS and normal tissue, and increase their tumor specificity and therapeutic performance. In this review, we briefly summarize the recent progress of passively-, actively-and biomimetically-targeting NDDS for cancer therapy.

参考文献

[1] Peer D, Karp J M, Hong S, et al. Nanocarriers as an emerging platform for cancer therapy[J]. Nature Nanotechnology, 2007, 2(12):751-760.
[2] Mann J. Natural products in cancer chemotherapy:Past, present and future[J]. Nature Reviews Cancer, 2002, 2(2):143-148.
[3] Petros R A, Desimone J M. Strategies in the design of nanoparticles for therapeutic applications[J]. Nature Reviews Drug Discovery, 2010, 9(8):615-627.
[4] Hassan S, Prakash G, Ozturk A, et al. Evolution and clinical translation of drug delivery nanomaterials[J]. Nano Today, 2017, 15:91-106.
[5] Veiga N, Goldsmith M, Granot Y, et al. Cell specific delivery of modified mRNA expressing therapeutic proteins to leukocytes[J]. Nature Communication, 2018, 9(1):4493.
[6] Szebeni J, Simberg D, González-Fernández Á, et al. Roadmap and strategy for overcoming infusion reactions to nanomedicines[J]. Nature Nanotechnology, 2018, doi:10.1038/s41565-018-0273-1.
[7] Liu Y, Jiang Y, Zhang M, et al. Modulating hypoxia via nanomaterials chemistry for efficient treatment of solid tumors[J]. Accounts of Chemical Research, 2018, 51(10):2502-2511.
[8] Anselmo A C, Mitragotri S. A review of clinical translation of inorganic nanoparticles[J]. AAPS Jounal, 2015, 17(5):1041-1054.
[9] Etheridge M L, Campbell S A, Erdman A G, et al. The big picture on nanomedicine:The state of investigational and approved nanomedicine products[J]. Nanomedicine, 2013, 9(1):1-14.
[10] Shi J, Kantoff P W, Wooster R, et al. Cancer nanomedicine:Progress, challenges and opportunities[J]. Nature Reviews Cancer, 2017, 17(1):20-37.
[11] Galic V L, Wright J D, Lewin S N, et al. Paclitaxel poliglumex for ovarian cancer[J]. Expert Opinion on Investigational Drugs, 2011, 20(6):813-821.
[12] Keefe S M, Hoffman-Censits J, Cohen R B, et al. Efficacy of the nanoparticle-drug conjugate CRLX101 in combination with bevacizumab in metastatic renal cell carcinoma:Results of an investigator-initiated phase I-Ⅱa clinical trial[J]. Annals of Oncology, 2016, 27(8):1579-1585.
[13] Tagami T, Ozeki T. Recent trends in clinical trials related to carrier-based drugs[J]. Journal of Pharmaceutical Sciences, 2017, 106(9):2219-2226.
[14] Duncan R, Sat Y N. Tumour targeting by enhanced permeability and retention (EPR) effect[J]. Annals of Oncology, 1998, 9:39-39.
[15] Torchilin V P. Multifunctional, stimuli-sensitive nanoparticulate systems for drug delivery[J]. Nature Reviews Drug Discovery, 2014, 13(11):813-827.
[16] Geretti E, Leonard S C, Dumont N, et al. Cyclophosphamidemediated tumor priming for enhanced delivery and antitumor activity of HER2-targeted liposomal doxorubicin (MM-302)[J]. Molecular Cancer Therapeutics, 2015, 14(9):2060-2071.
[17] Camp E R, Wang C, Little E C, et al. Transferrin receptor targeting nanomedicine delivering wild-type p53 gene sensitizes pancreatic cancer to gemcitabine therapy[J]. Cancer Gene Theray, 2013, 20(4):222-228.
[18] Tanaka T, Shiramoto S, Miyashita M, et al. Tumor targeting based on the effect of enhanced permeability and retention (EPR) and the mechanism of receptor-mediated endocytosis (RME)[J]. International Journal of Pharmaceutics, 2004, 277(1-2):39-61.
[19] Prabhakar U, Maeda H, Jain R K, et al. Challenges and key considerations of the enhanced permeability and retention effect for nanomedicine drug delivery in oncology[J]. Cancer Research, 2013, 73(8):2412-2417.
[20] Nehoff H, Parayath N N, Domanovitch L, et al. Nanomedicine for drug targeting:Strategies beyond the enhanced permeability and retention effect[J]. International Journal of Nanomedicine, 2014, 9:2539-2555.
[21] Du J Z, Li H J, Wang J. Tumor-acidity-cleavable maleic acid amide (TACMAA):A powerful tool for designing smart nanoparticles to overcome delivery barriers in cancer nanomedicine[J]. Accounts of Chemical Research, 2018, doi:10.1021/acs.accounts.8b00195.
[22] Zhang P, Wang J, Chen H, Zhao L, et al. Tumor microenvironment-responsive ultrasmall nanodrug generators with enhanced tumor delivery and penetration[J]. Journal of American Chemistry Society, 2018, doi:10.1021/jacs.8b09396.
[23] Zhou F Y, Feng B, Wang T T, et al. Programmed multiresponsive vesicles for enhanced tumor penetration and combination therapy of triple-negative breast cancer[J]. Advanced Functional Materials, 2017, 27(20):1606530.
[24] Guan X W, Guo Z P, Wang T H, et al. A pH-responsive detachable peg shielding strategy for gene delivery system in cancer therapy[J]. Biomacromolecules, 2017, 18(4):1342-1349.
[25] Wang D G, Wang T T, Liu J P, et al. Acid-activatable versatile micelleplexes for PD-L1 blockade enhanced cancer photodynamic immunotherapy[J]. Nano Letters, 2016, 16(9):5503-5513.
[26] Wang H X, Zuo Z Q, Du J Z, et al. Surface charge critically affects tumor penetration and therapeutic efficacy of cancer nanomedicines[J]. Nano Today, 2016, 11(2):133-144.
[27] Lee Y, Fukushima S, Bae Y, et al. A protein nanocarrier from charge-conversion polymer in response to endosomal pH[J]. Journal of the American Chemical Society, 2007, 129(17):5362-5364.
[28] Yuan Y Y, Mao C Q, Du X J, et al. Surface charge switchable nanoparticles based on zwitterionic polymer for enhanced drug delivery to tumor[J]. Advanced Materials, 2012, 24(40):5476-5480.
[29] Liu L H, Qiu W X, Zhang Y H, et al. A charge reversible self-delivery chimeric peptide with cell membrane-targeting properties for enhanced photodynamic therapy[J]. Advanced Functional Materials, 2017, 27(25):1700220.
[30] Bertrand N, Wu J, Xu X Y, et al. Cancer nanotechnology:The impact of passive and active targeting in the era of modern cancer biology[J]. Advanced Drug Delivery Reviews, 2014, 66:2-25.
[31] Li H J, Du J Z, Liu J, et al. Smart superstructures with ultrahigh ph-sensitivity for targeting acidic tumor microenvironment:Instantaneous size switching and improved tumor penetration[J]. ACS Nano, 2016, 10(7):6753-6761.
[32] Li H J, Du J Z, Du X J, et al. Stimuli-responsive clustered nanoparticles for improved tumor penetration and therapeutic efficacy[J]. PNAS, 2016, 113(15):4164-4169.
[33] Chen J J, Ding J X, Wang Y C, et al. Sequentially responsive shell-stacked nanoparticles for deep penetration into solid tumors[J]. Advanced Materials, 2017, 29(32):201701170.
[34] Su J H, Sun H P, Meng Q S, et al. Long circulation redblood-cell-mimetic nanoparticles with peptide-enhanced tumor penetration for simultaneously inhibiting growth and lung metastasis of breast cancer[J]. Advanced Functional Materials, 2016, 26(8):1243-1252.
[35] Rao L, Bu L L, Xu J H, et al. Red blood cell membrane as a biomimetic nanocoating for prolonged circulation time and reduced accelerated blood clearance[J]. Small, 2015, 11(46):6225-6236.
[36] Mou X B, Ali Z S, Li S, et al. Applications of magnetic nanoparticles in targeted drug delivery system[J]. Journal of Nanoscience and Nanotechnology, 2015, 15(1):54-62.
[37] Yang Z, Fan W, Tang W, Shen Z, et al. Near-infrared semiconducting polymer brush and pH/GSH-responsive polyoxometalate cluster hybrid platform for enhanced tumor-specific phototheranostics[J]. Angewandte Chemie International Edition, 2018, 57(43):14101-14105.
[38] Costa DF, Mendes LP, Torchilin VP. The effect of low-and high-penetration light on localized cancer therapy[J]. Advanced Drug Delivery Review, 2018, doi:10.1016/j.addr.2018.09.004.
[39] Matera C, Gomila A M J, Camarero N, et al, Photoswitchable antimetabolite for targeted photoactivated chemotherapy[J]. Journal American Chemistry Society, 2018, doi:10.1021/jacs.8b08249.
[40] Ni J S, Zhang P, Jiang T, et al. Red/NIR-emissive benzo[d]imidazole-cored AIEgens:Facile molecular design for wavelength extending and in vivo tumor metabolic imaging[J]. Advanced Materials, 2018, doi:10.1002/adma.201805220.
[41] Liu Y, Bhattarai P, Dai Z, Chen X. Photothermal therapy and photoacoustic imaging via nanotheranostics in fighting cancer[J]. Chemistry Society Review, 2018, doi:10.1039/c8cs00618k.
[42] Yu H J, Cui Z R, Yu P C, et al. pH and near-infrared lightresponsive micelles with hyperthermia-triggered tumor penetration reverse multidrug resistance in breast cancer[J]. Advanced Functional Materials, 2016, 12(2):461-461.
[43] Tay Z W, Chandrasekharan P, Chiu-Lam A, et al. Magnetic particle imaging-guided heating in vivo using gradient fields for arbitrary localization of magnetic hyperthermia therapy[J]. ACS Nano, 2018, 12(4):3699-3713.
[44] Pan X T, Bai L X, Wang H, et al. Metal-organic-frameworkderived carbon nanostructure augmented sonodynamic cancer therapy[J]. Advanced Materials, 2018, 30(23):1800180
[45] Wang X Y, Li Y M, Li Q S, et al. Hyaluronic acid modification of RNase A and its intracellular delivery using lipid-like nanoparticles[J]. Journal of Controlled Release, 2017, 263:39-45.
[46] Yang R, Xu J, Xu L, et al. Cancer cell membrane-coated adjuvant nanoparticles with mannose modification for effective anticancer vaccination[J]. ACS Nano, 2018, 12(6):5121-5129.
[47] Qiao C, Yang J, Shen Q, et al. Traceable nanoparticles with dual targeting and ros response for rnai-based immunochemotherapy of intracranial glioblastoma treatment[J]. Advanced Materials, 2018, 30(18):1705054.
[48] Wang Y, Xie Y, Li J, et al. Tumor-penetrating nanoparticles for enhanced anticancer activity of combined photodynamic and hypoxia-activated therapy[J]. ACS Nano, 2017, 11(2):2227-2238.
[49] Xu X, Saw P E, Tao W, et al. ROS-responsive polyprodrug nanoparticles for triggered drug delivery and effective cancer therapy[J]. Advanced Materials, 2017, 29(33):201700141.
[50] Ahn J, Miura Y, Yamada N, et al. Antibody fragment-conjugated polymeric micelles incorporating platinum drugs for targeted therapy of pancreatic cancer[J]. Biomaterials, 2015, 39:23-30.
[51] Wang T, Wang D, Liu J, et al. Acidity-triggered ligand-presenting nanoparticles to overcome sequential drug delivery barriers to tumors[J]. Nano Letters, 2017, 17(9):5429-5436.
[52] Li D, Ma Y, Du J, et al. Tumor acidity/NIR controlled interaction of transformable nanoparticle with biological systems for cancer therapy[J]. Nano Letters, 2017, 17(5):2871-2878.
[53] Li J, Zhen X, Lyu Y, et al. Cell membrane coated semiconducting polymer nanoparticles for enhanced multimodal cancer phototheranostics[J]. ACS Nano, 2018, 12(8):8520-8530.
[54] Fang R H, Hu C M J, Luk B T, et al. Cancer cell membranecoated nanoparticles for anticancer vaccination and drug delivery[J]. Nano Letters, 2014, 14(4):2181-2188.
[55] Hu C M J, Zhang L, Aryal S, et al. Erythrocyte membranecamouflaged polymeric nanoparticles as a biomimetic delivery platform[J]. PNAS, 2011, 108(27):10980-10985.
[56] Aizik G, Waiskopf N, Agbaria M, et al. Delivery of liposomal quantum dots via monocytes for imaging of inflamed tissue[J]. ACS Nano, 2017, 11(3):3038-3051.
[57] Lang T Q, Dong X Y, Huang Y, et al. Ly6C(hi) monocytes delivering ph-sensitive micelle loading paclitaxel improve targeting therapy of metastatic breast cancer[J]. Advanced Functional Materials, 2017, 27(26):1701093.
[58] He X Y, Cao H Q, Wang H, et al. Inflammatory monocytes loading protease-sensitive nanoparticles enable lung metastasis targeting and intelligent drug release for anti-metastasis therapy[J]. Nano Letters, 2017, 17(9):5546-5554.
[59] Chambers E, Mitragotri S. Long circulating nanoparticles via adhesion on red blood cells:Mechanism and extended circulation[J]. Experimental Biology and Medicine, 2007, 232(7):958-966.
[60] Sun H P, Su J H, Meng Q S, et al. Cancer-cell-biomimetic nanoparticles for targeted therapy of homotypic tumors[J]. Advanced Materials, 2016, 28(43):9581-9588.
[61] Cao H Q, Dan Z L, He X Y, et al. Liposomes coated with isolated macrophage membrane can target lung metastasis of breast cancer[J]. ACS Nano, 2016, 10(8):7738-7748.
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