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化学进展 2021, Vol. 33 Issue (10): 1900-1916 DOI: 10.7536/PC200956 前一篇   

• 综述 •

纳米载体在共负载siRNA及化疗药物对逆转肿瘤多药耐药性方面的应用

杨强强1, 李川1, 于淑娴1, 范书华1, 王月霞2, 洪敏1,*()   

  1. 1 聊城大学化学化工学院 聊城 252059
    2 齐鲁工业大学(山东省科学院)山东省高校轻工精细化学品重点实验室 化学与制药工程学院 济南 250353
  • 收稿日期:2020-09-28 修回日期:2020-12-02 出版日期:2021-10-20 发布日期:2020-12-22
  • 通讯作者: 洪敏
  • 基金资助:
    国家自然科学基金项目(91543206); 山东省自然科学基金项目(ZR2015BM024); 山东省“泰山学者” 研究经费和聊城大学研究基金(318012026)
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Application of Nanocarriers in Co-Loading siRNA and Chemotherapeutic Drugs to Reverse Multidrug Resistance of Tumor

Qiangqiang Yang1, Chuan Li1, Shuxian Yu1, Shuhua Fan1, Yuexia Wang2, Min Hong1()   

  1. 1 School of Chemistry and Chemical Engineering, Liaocheng University,Liaocheng 252059, China
    2 Key Laboratory of Fine Chemicals in Universities of Shandong, School of Chemistry and Pharmaceutical Engineering, Qilu University of Technology(Shandong Academy of Sciences),Jinan 250353, China
  • Received:2020-09-28 Revised:2020-12-02 Online:2021-10-20 Published:2020-12-22
  • Contact: Min Hong
  • Supported by:
    National Natural Science Foundation of China(91543206); Natural Science Foundation of Shandong Province(ZR2015BM024); Tai-Shan Scholar Research Fund of Shandong Province and Research Foundation of Liaocheng University(318012026)

近年来,基于小干扰RNA(siRNA)的基因干扰技术从基因水平上调节与肿瘤产生多药耐药性相关的各种蛋白进而逆转化疗多药耐药性方面表现出了巨大的应用潜力。鉴于此,研究者们在RNA干扰与化疗药物的协同抗癌方面做了大量工作。但游离的siRNA在无载体的情况下不易被细胞吸收,而且会被血浆和组织中内源性的核糖核酸酶降解,因此必须将siRNA负载在载体上才能有效应用于肿瘤治疗。鉴于纳米载体的安全、高效及靶向性等优点,人们已经发展出大量能同时负载siRNA及化疗药物的纳米复合体系。本文主要评述了近年来报道的一些纳米材料在共负载siRNA及化疗药物对逆转肿瘤多药耐药性方面的应用,以及研究中经常用到的一些逆转多药耐药的作用靶点。

关键词： RNA干扰技术, 基因调控, 逆转多药耐药性, 纳米载体

In recent years, gene interference technology based on small interfering RNA(siRNA) has shown great potential in reversing multidrug resistance of chemotherapy by regulating various proteins related to multidrug resistance of tumor at the gene level. In view of this, the researchers have done a lot of work in the area of RNA interference and chemotherapy drugs. But the free siRNA is not easy to be absorbed by cells without carrier, and it will be degraded by endogenous ribonuclease in plasma and tissues. Therefore, it is necessary to load siRNA on the carrier in order to effectively apply it to tumor treatment. In view of the safety, high efficiency and targeting of nanocarriers, a large number of nanocomposite systems have been developed which can simultaneously load siRNA and chemotherapy drugs. In this paper, the application of nanomaterials in co-loading siRNA and reversing multidrug resistance of chemotherapy drugs are reviewed. In addition, in order to have a better understanding of the related work, some targets which are often used in the study to reverse multidrug resistance are also briefly described.

Contents

1 Introduction

2 Main targets of siRNA regulation

2.1 ATP-binding cassette transporters

2.2 Apoptosis related proteins

2.3 Other targets

3 Nanocarriers for co-delivery of siRNA and chemotherapeutic drugs

3.1 Mesoporous silica nanoparticles

3.2 Metal-organic frameworks

3.3 Polymeric micelles

3.4 Liposome/Niosome

3.5 Dendrimer

3.6 Layer-by-layer nanoparticles

3.7 Hyaluronic acid nanosystem

3.8 Summary

4 Expansion

5 Conclusion and outlook

Key words: RNA interference technology, gene regulation, reversal of multidrug resistance, nanocarrier
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图1 DOX-MSN-COOH@ZIF-8/Bcl-2 siRNA NPs示意图[61]
Fig.1 Schematic illustration of the Synthesis of DOX-MSN-COOH@ZIF-8/Bcl-2 siRNA NPs[61]. Copyright 2018, American Chemical Society
图2 功能性金属有机骨架纳米药物的合成方法及响应机理[73]
Fig. 2 Synthesis process and response mechanism for functional metal-organic framework-based nanodrug(DOX@AMOFs@DRHC/CPPs)[73]. Copyright 2017, American Chemical Society
图3 结合靶向药物“赫赛汀”并负载DTX的TPGS-siPlk1/TPGS胶束(micSDH)制备示意图[76]
Fig. 3 Preparation of TPGS-siPlk1/TPGS micelles(micSDH) combined with targeted drug Herceptin and DTX[76]
图4 三嵌段共聚物胶束mPEG45-b-PCL80-b-PPEEA制备及载药示意图[80]
Fig. 4 Schematic diagram of the preparation and drug-loading of triblock copolymer micelle mPEG45-b-PCL80-b-PPEEA[80]. Copyright 2011, American Chemical Society
图5 自组装脂质纳米粒共同递送Pt(Ⅳ)前药-DSCP和靶向XPF的siRNA的示意图。释放出DSCP破坏DNA的同时携带siRNA到细胞中,特异性下调XPF mRNA和蛋白质表达,从而增强铂类药物的作用[83]
Fig. 5 Schematic view of our design to co-deliver the Pt(Ⅳ) prodrug DSCP and XPF-targeted siRNA using self-assembled lipid nanoparticles. Cisplatin prodrug DSCP is released and activated to damage DNA. At the same time, siRNA is carried into cells and specifically down-regulates both mRNA and protein levels of endonuclease XPF to prevent the repair of Pt-DNA damage to potentiate the platinum drug[83].Copyright 2019, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
图6 使用可生物降解PSomes来递送Bcl-xL siRNA和DOX的共递送系统的示意图.(i)Bcl-xL-siRNA直接包埋在PSomes(SPSomes)中;(ii)然后通过疏水作用将DOX装入SPSomes的壳中形成CPSomes[93]
Fig. 6 Schematic illustration of the co-delivery system using biodegradable PSomes to deliver Bcl-xL siRNA and DOX.(i) Bcl-xL siRNA is directly encapsulated into PSomes(SPSomes).(ii) DOX is then loaded into the shell of SPSomes through hydrophobic interaction to form CPSomes[93]. Copyright 2013, WILEY-VCH Verlag GmbH & Co
图7 层层组装纳米颗粒示意图[97]
Fig. 7 Schematic diagram of layer-by-layer nanoparticle[97]. Copyright 2013, American Chemical Society
图8 siRNA/DOX/GH-DPP纳米粒制备以及在体内循环及细胞内作用示意图.(1)siRNA/DOX/GH-DPP纳米粒的制备(2)经血液循环,肝靶向药物传递(3)细胞摄取(4)pH触发的Bcl-2 siRNA和DOX释放[101]
Fig. 8 Schematic illustration of (1)preparation of siRNA/DOX/GH-DPP nanoparticles(2)liver-targeted drug delivery via blood cycle(3)cellular uptake(4)pH-triggered release of Bcl-2 siRNA and DOX[101]. Copyright 2019
表1 共负载siRNA和化疗药物纳米体系汇总表
Table 1 Summary of co-loaded siRNA and chemotherapeutic drug nanosystems
Materials for
surface modification		 Drug siRNA Substances with targeting effect Release conditions References Advantages of carrier Deficiency of carrier
MSN PEI-PEG DOX P-gp、Bcl-2、c-Myc、PXR - Acidic 56 Biological stability;
Low toxicity;
Biodegradable;Modifiability;High
porosity; Uniform
and adjustable
aperture; Better load capacity		 Risk of hemolysis; Complicated preparation
ZIF-8 DOX Bcl-2 - Lysosome 57
PEG DOX T-type Ca2+
channel		 - Acidic 58
S-S bond、PAE DOX P-gp - Reductive(GSH) 59
PEI DOX P-gp - Reductive(GSH) 62
CA PTX
DTX		 AKT
ERBB2		 - Acidic 63
LDHs Se P-gp
β-tubulin Ⅲ		 - Biodegradation 65
Ca/P/Liposome DTX GRP78 RGD Biodegradation 36
MOF UiO DPP P-gp、Bcl-2
Survivin		 - Phosphate 68 Biodegradable; High porosity; Large
specific surface area; Better load capacity; self-assembly		 Poor biocompatibility; poor drug release propertie
MIL-101 Se、Ru P-gp - Biodegradation 69
AMOFS DOX HIF-1α CPPS Azoreduction 70
Polym
ericmi
celles		 LDL NSC-SS-UA PTX BCRP LDL Reductive (GSH)、Acidic 71 High stability in
vivo; Controlled drug release; Functional design		 Poor storage
stability; Toxicity;
Prepared by
chemical reaction
TPGS DTX PLK1 Herceptin Reductive (GSH)、Acidic 72
HA-ss-(OA-g-bPEI) PTX AURKA HA Reductive(GSH) 73
C18-N
DSPE-PEG2000		 DOX PLK1 - Acidic 74
DPA+PEI PTX Akt - Acidic 75
mPEG45-b-PCL80-b-PPEEA PTX PLK1 - Biodegradation 76
Liposome/
Niosome		 DOTAP、CHOL
DSPE-mPEG DPPC		 PTX GAPDH - Biodegradation 78 Easy assembly; High
entrapment efficiency; Narrow
size distribution;
Controlled drug
release		 Poor storage
stability; High-cost
DOTAP、CHOLDSPE-
mPEG DOPE		 DSCP XPF - Acidic 79
PRTM、DOPE
DDCTMA		 PTX survivin - Biodegradation 80
PRTM、DOTAP
CHOL		 Gem Mcl-1 - Biodegradation 81
mPEG-PLGA
EPL、PEG		 Gem HIF-1a - Biodegradation 82
LHSSG2C14 SPC、CHOL PTX Survivin - Reductive(GSH) 83
PRTM、DOPE
CHOL		 DOX Fab - Biodegradation 84
EDOPC PTX Mcl-1 - Biodegradation 86
LDL、DOPE
CHOLDSPE-PEG		 PTX Bcl-2 - Biodegradation 87
Span80、DOTAP DOX Bcl-2 BCRP - Biodegradation 88
mPEG-b-PLA DOX Bcl-xl - Biodegradation 89
Dendrimer Fol-PEG-GUG-β-CDE DOX PLK1 FA Acidic 92 Structural uniformity; Easily
attached		 Toxicity; Complicated preparation
LbL AuNP IM STAT3 - Biodegradation 94 Modular design;
Modifiability; Controlled drug
release;		 Poor bearing
capacity; Less
available materials
PLA、HA DOX MRP1 HA Biodegradation 95
HA CaP、DPA/ZnHA-CA DOX P-gp HA Acidic 96 Biocompatibility; Targetability; Modifiability; High
degradability;		 Poor bearing
capacity; Uncontrolled drug
release
DSPE-PEG-PEIGA-HA DOX Bcl-2 GA-HA Acidic 97
表2 缩略语表
Table 2 List of abbreviation
Abbreviation full name Abbreviation full name
MDR multi-drug resistence
(多药耐药)		 DSCP disuccinatocisplatin
(琥珀酸顺铂)
P-gp P-glycoprotein
(P-糖蛋白)		 IM imatinib mesylate
(甲磺酸伊马替尼)
MRP1 multidrug resistance-associated protein 1
(多药耐药相关蛋白1)		 GST glutathione S-transferase
(谷胱甘肽巯基转移酶)
BCRP breast cancer resistance protein
(乳腺癌耐药蛋白)		 MGMT O6-methyguanine-DNA methytransferase
(O6-甲基鸟嘌呤-DNA-甲基转移酶)
Bcl-2 B-cell lymphoma-2
(B淋巴细胞瘤-2基因)		 RRM2 ribonucleotide reductase M2
(核糖核苷酸还原酶M2)
Mcl-1 myeloid cell leukemia 1
(一种凋亡调控基因)		 GAPDH glyceraldehyde-3-phosphate Dehydrogenase
(甘油醛-3-磷酸脱氢酶)
PLK1 Polo-like Kinase 1
(Polo样蛋白质激酶1)		 HIF-1 hypoxia-inducible factor-1
(缺氧诱导因子1)
EPR
效应		 enhanced permeability and retention effect
(高渗透长滞留效应)		 c-Myc 一种可使细胞无限增殖的基因
RES
系统		 reticuloendothelial system
(网状内皮系统)		 MSN mesoporous Silica Nanoparticles
(介孔二氧化硅)
CPPs cell penetrating peptide
(细胞穿透肽)		 MON mesoporous Organosilica Nanoparticles
(介孔有机二氧化硅)
LDL low-density Lipoprotein
(低密度脂蛋白)		 MOF metal-Organic Frameworks
(金属有机框架)
PXR pregnane X receptor
(孕烷X受体)		 DPA dipicolylamine
(二甲基吡啶胺)
PAE poly (β-amino esters)
(聚β-氨基酯)		 PRTM protamine
(鱼精蛋白)
DPPC 1,2-Dihexadecanoyl-rac-glycer0-3-phosp
(二棕榈酰磷脂酰胆碱)		 EPL ε-polylysine
(ε-聚赖氨酸)
DOTAP N-[1-(2,3-dioleyloxy)proply]-N,N,
N-trimethylammonium chloridep
(1,2-二油酰-3-三甲基丙烷基氯化铵)		 DOPE dioleoyl Phosphoethanolamine
(二油酰基磷脂酰乙醇胺)
XPF xeroderma pigmentosum complementation group F
(F组着色性干皮病偶联因子重组蛋白)		 DSPE 1,2-distearoyl-sn-glycero-3-phosphoethanolamine
(二硬脂酰基磷脂酰乙醇胺)
[1]
Garcia-Mayea Y, Mir C, Masson F, Paciucci R, LLeonart M E. Semin. Cancer Biol., 2020, 60: 166.

doi: S1044-579X(19)30164-6     pmid: 31369817
[2]
Lin G, Chen S Y, Mi P. J. Biomed. Nanotechnol., 2018, 14(7): 1189.

doi: 10.1166/jbn.2018.2546     URL    
[3]
Li K, Lai H. Biomed. Pharmacother., 2017, 96: 371.

doi: 10.1016/j.biopha.2017.10.016     URL    
[4]
Lu J F, Pokharel D, Bebawy M. Drug Deliv. Transl. Res., 2017, 7(2): 276.
[5]
Zhang Y K, Zhang X Y, Zhang G N, Wang Y J, Xu H Z, Zhang D M, Shukla S, Liu L L, Yang D H, Ambudkar S V, Chen Z S. Biochem. Pharmacol., 2017, 132: 29.

doi: 10.1016/j.bcp.2017.02.019     URL    
[6]
Li X Q, Wang L, Lei Y, Hu T, Zhang F L, Cho C H, To K K W. Eur. J. Med. Chem., 2015, 101: 560.

doi: 10.1016/j.ejmech.2015.06.049     URL    
[7]
Wang J Q, Li J Y, Teng Q X, Lei Z N, Ji N, Cui Q B, Zeng L L, Pan Y H, Yang D H, Chen Z S. Cancers, 2020, 12(2): 466.

doi: 10.3390/cancers12020466     URL    
[8]
Ma J, Zhao Z X, Wu K M, Xu Z, Liu K Z. Gene, 2016, 587(2): 147.

doi: 10.1016/j.gene.2016.04.054     URL    
[9]
Li H Y, Luo F, Li X Y, Fu X F, He J F, Tian Y Z, Zhu J J, Chu X Y, Zhao H L. Anti Cancer Agents Med. Chem., 2019, 19(6): 740.

doi: 10.2174/1871520619666190301145637     URL    
[10]
Tong X J, Zhao J, Zhang Y H, Mu P, Wang X B. Oncol. Lett., 2019: 1 8:22.
[11]
Liu H X, Liao Y, Tang M, Wu T, Tan D L, Zhang S X, Wang H D. Cancer Med., 2018, 7(5): 1921.

doi: 10.1002/cam4.2018.7.issue-5     URL    
[12]
Tsouris V, Joo M K, Kim S H, Kwon I C, Won Y Y. Biotechnol. Adv., 2014, 32(5): 1037.

doi: 10.1016/j.biotechadv.2014.05.006     URL    
[13]
Wang J, Mi P, Lin G, Wáng Y X, Liu G, Chen X. Adv., Drug Deliv. Rev., 2016, 104: 44.
[14]
Uchino K, Ochiya T, Takeshita F. Jpn. J. Clin. Oncol., 2013, 43(6): 596.

doi: 10.1093/jjco/hyt052     pmid: 23592885
[15]
Qiao C M, Yang J, Shen Q, Liu R Y, Li Y H, Shi Y J, Chen J L, Shen Y Q, Xiao Z B, Weng J, Zhang X. Adv. Mater., 2018, 30(18): 1705054.

doi: 10.1002/adma.201705054     URL    
[16]
Crouchet E, Saad R, Affolter-Zbaraszczuk C, Ogier J, Baumert T F, Schuster C, Meyer F. J. Mater. Chem. B, 2017, 5(4): 858.

doi: 10.1039/c6tb01718e     pmid: 32263854
[17]
刘颖(Liu Y,), 赵俐(Zhao L). 医药导报(Herald of Medicine), 2018, 37(05): 581.
[18]
Wagstaff K, Jans D. Curr. Med. Chem., 2006, 13(12): 1371.

pmid: 16719783
[19]
Chen S H, Zhaori G T. Eur. J. Clin. Investig., 2011, 41(2): 221.
[20]
Layzer J M, McCaffrey A P, Tanner A K, Huang Z, Kay M A, Sullenger B A. RNA, 2004, 10: 766.
[21]
van de Water F M, Boerman O C, Wouterse A C, Peters J G P, Russel F G M, Masereeuw R. Drug Metab. Dispos., 2006, 34(8): 1393.

doi: 10.1124/dmd.106.009555     URL    
[22]
Mosser D M, Edwards J P. Nat. Rev. Immunol., 2008, 8(12): 958.

doi: 10.1038/nri2448     pmid: 19029990
[23]
Singha K, Namgung R, Kim W J. Nucleic Acid Ther., 2011, 21(3): 133.

doi: 10.1089/nat.2011.0293     URL    
[24]
Mu L, Feng S S. J. Control. Release, 2003, 86(1): 33.

doi: 10.1016/S0168-3659(02)00320-6     URL    
[25]
Saggar J K, Fung A S, Patel K J, Tannock I F. Mol. Cancer Ther., 2013, 12(4): 542.

doi: 10.1158/1535-7163.MCT-12-0967     URL    
[26]
Murakami M, Cabral H, Matsumoto Y, Wu S, Kano M R, Yamori T, Nishiyama N, Kataoka K. Sci. Transl. Med., 2011, 3(64): 64ra2.
[27]
Yan Y, Ochs C J, Such G K, Heath J K, Nice E C, Caruso F. Adv. Mater., 2010, 22(47): 5398.

doi: 10.1002/adma.201003162    
[28]
Li T A, Xu D H, Gao J Q. Chin. Pharm. J., 2016, 51: 1360.
[29]
Majidinia M, Mirza-Aghazadeh-attari M, Rahimi M, Mihanfar A, Karimian A, Safa A M, Yousefi B. IUBMB Life, 2020, 72(5): 855.

doi: 10.1002/iub.2215     pmid: 31913572
[30]
Wang H X, Zhao Y X, Wang H Y, Gong J B, He H N, Shin M C, Yang V C, Huang Y Z. J. Control. Release, 2014, 192: 47.

doi: 10.1016/j.jconrel.2014.06.051     URL    
[31]
牛星燕(Niu X Y,), 张冬萍(Zhang D P,), 李飞霞(Li F X). 国际妇产科学杂志(Journal of International Obstetrics and Gynecology), 2020, 47(2): 125.
[32]
左鹏(Zuo P,), 李小平(Li X P). 实用妇产科杂志(Journal of Practical Obstetrics and Gynecology), 2020, 36(2): 83.
[33]
李勇威(Li Y W,), 靳晓伟(Jin X W,), 王红(Wang H,), 刘亚男(Liu Y N,), 汪海岩(Wang H Y). 医学研究杂志(Journal of Medical Research), 2020, 49(7): 136.
[34]
Wang Y, Qin L, Chen W, Chen Q, Sun J, Wang G. Eur. J. Med.Chem.. 2021, 226:113806.
[35]
Ni Q Q, Zhang F W, Zhang Y L, Zhu G Z, Wang Z, Teng Z G, Wang C Y, Yung B C, Niu G, Lu G M, Zhang L J, Chen X Y. Adv. Mater., 2018, 30(10): 1870064.

doi: 10.1002/adma.v30.10     URL    
[36]
Sun L J, Wang D G, Chen Y, Wang L Y, Huang P, Li Y P, Liu Z W, Yao H L, Shi J L. Biomaterials, 2017, 133: 219.

doi: 10.1016/j.biomaterials.2017.04.028     URL    
[37]
Mi P, Cabral H, Kataoka K. Adv. Mater., 2020, 32(13): 2070101.

doi: 10.1002/adma.v32.13     URL    
[38]
Liu J H, Zhao Y X, Guo Q Q, Wang Z, Wang H Y, Yang Y X, Huang Y Z. Biomaterials, 2012, 33(26): 6155.

doi: 10.1016/j.biomaterials.2012.05.035     URL    
[39]
Zhang M, Liu E G, Cui Y N, Huang Y Z. Cancer Biol. Med., 2017, 14(3): 212.

doi: 10.20892/j.issn.2095-3941.2017.0054     pmid: 28884039
[40]
Conseil G, Arama-Chayoth M, Tsfadia Y, Cole S P C. FASEB J., 2019, 33(10): 10692.
[41]
Grant C E, Gao M, DeGorter M K, Cole S P C, Deeley R G. Drug Metab. Dispos., 2008, 36(12): 2571.

doi: 10.1124/dmd.108.022491     URL    
[42]
Wong I L K, Zhu X Z, Chan K F, Law M C, Lo A M Y, Hu X S, Chow L M C, Chan T H. J. Med. Chem., 2018, 61(22): 9931.

doi: 10.1021/acs.jmedchem.8b00834     URL    
[43]
Yang J, Zhang B B, Qin Z F, Li S S, Xu J J, Yao Z H, Zhang X J, Gonzalez F J, Yao X S. BioFactors, 2018, 44(6): 558.

doi: 10.1002/biof.v44.6     URL    
[44]
Mao Q, Unadkat J D,. AAPS J., 2005, 7: E118.
[45]
Nakanishi T, Ross D D. Chin. J. Cancer, 2012, 31(2): 73.

doi: 10.5732/cjc.011.10320     pmid: 22098950
[46]
Reustle A, Fisel P, Renner O, Büttner F, Winter S, Ransch S, Kruck S, Nies A T, Hennenlotter J, Scharpf M, Fend F, Stenzl A, Bedke J, Schwab M, Schaeffeler E. Experimental and Molecular Therapeutics. Int. J. Cancer, 2018, 143:3181.

doi: 10.1002/ijc.31741     pmid: 30070687
[47]
Yuan Y L, Cai T G, Xia X, Zhang R H, Chiba P, Cai Y. Drug Deliv., 2016, 23(9): 3350.

doi: 10.1080/10717544.2016.1178825     URL    
[48]
Gottesman M M. Annu. Rev. Med., 2002, 53(1): 615.

doi: 10.1146/med.2002.53.issue-1     URL    
[49]
Adams J M, Cory S. Curr. Opin. Immunol., 2007, 19(5): 488.

doi: 10.1016/j.coi.2007.05.004     URL    
[50]
Yang C B, Chan K K, Lin W J, Soehartono A M, Lin G M, Toh H, Yoon H S, Chen C K, Yong K T. Nano Res., 2017, 10(9): 3049.
[51]
Yan X, Yu Q S, Guo L Y, Guo W X, Guan S L, Tang H, Lin S S, Gan Z H. ACS Appl. Mater. Interfaces, 2017, 9(8): 6804.

doi: 10.1021/acsami.6b14244     URL    
[52]
Prevarskaya N, Ouadid-Ahidouch H, Skryma R, Shuba Y. Phil. Trans. R. Soc. B, 2014, 369(1638): 20130097.

doi: 10.1098/rstb.2013.0097     URL    
[53]
Dziegielewska B, Casarez E V, Yang W Z, Gray L S, Dziegielewski J, Slack-Davis J K. Mol. Cancer Ther., 2016, 15(3): 460.

doi: 10.1158/1535-7163.MCT-15-0456     pmid: 26832797
[54]
Chen J R, Jia X H, Wang H, Yi Y J, Wang J Y, Li Y J. Int. J. Oncol., 2016, 48(5): 2063.

doi: 10.3892/ijo.2016.3423     URL    
[55]
Powell D, Chandra S, Dodson K, Shaheen F, Wiltz K, Ireland S, Syed M, Dash S, Wiese T, Mandal T, Kundu A. Eur. J. Pharm. Biopharm., 2017, 114: 108.

doi: S0939-6411(17)30119-4     pmid: 28131717
[56]
Ai Z H, Lu Y, Qiu S B, Fan Z. Cancer Lett., 2016, 373(1): 36.
[57]
Zhang Q, Shi J Z, Yuan F, Wang H H, Fu W H, Pan J H, Huang Y Q, Yu J, Yang J, Chen Z W. Int. J. Cancer, 2016, 139(12): 2827.

doi: 10.1002/ijc.30396     pmid: 27542841
[58]
Liu H, Liu T, Zhou Y, Song X, Wei R. Oncol. Lett., 2020, 19: 1993.
[59]
Chen A M, Zhang M, Wei D G, Stueber D, Taratula O, Minko T, He H X. Small, 2009, 5(23): 2673.

doi: 10.1002/smll.v5:23     URL    
[60]
Meng H, Mai W X, Zhang H Y, Xue M, Xia T, Lin S J, Wang X, Zhao Y, Ji Z X, Zink J I, Nel A E. ACS Nano, 2013, 7(2): 994.

doi: 10.1021/nn3044066     URL    
[61]
Pan Q S, Chen T T, Nie C P, Yi J T, Liu C, Hu Y L, Chu X. ACS Appl. Mater. Interfaces, 2018, 10(39): 33070.

doi: 10.1021/acsami.8b13393     URL    
[62]
Wang S, Liu X, Chen S Z, Liu Z R, Zhang X D, Liang X J, Li L L. ACS Nano, 2019, 13: 2663., 2019, 13: 274.
[63]
Huang I P, Sun S P, Cheng S H, Lee C H, Wu C Y, Yang C S, Lo L W, Lai Y K. Mol. Cancer Ther., 2011, 10(5): 761.

doi: 10.1158/1535-7163.MCT-10-0884     pmid: 21411714
[64]
M Wu, Q Meng, Y Chen, Y Du, L Zhang, Y Li, L Zhang, J Shi. Adv. Mater. Weinheim, 2015, 27: 215.
[65]
Wu M Y, Meng Q S, Chen Y, Zhang L X, Li M L, Cai X J, Li Y P, Yu P C, Zhang L L, Shi J L. Adv. Mater., 2016, 28(10): 1963.

doi: 10.1002/adma.201505524     URL    
[66]
Fatemian T, Moghimi H R, Chowdhury E H. Pharmaceutics, 2019, 11(9): 458.

doi: 10.3390/pharmaceutics11090458     URL    
[67]
Hu H B, Li G X, Wang L, Watts J, Combs G F, Lü J. Clin. Cancer Res., 2008, 14(4): 1150.

doi: 10.1158/1078-0432.CCR-07-4037     URL    
[68]
Zheng W J, Yin T T, Chen Q C, Qin X Y, Huang X Q, Zhao S, Xu T Y, Chen L M, Liu J. Acta Biomater., 2016, 31: 197.

doi: 10.1016/j.actbio.2015.11.041     URL    
[69]
Zhang X Y, He Z L, Xiang L Q, Li L, Zhang H Y, Lin F Z, Cao H Y. Drug Des. Dev. Ther., 2019, 13: 1357.

doi: 10.2147/DDDT     URL    
[70]
Rieter W J, Pott K M, Taylor K M L, Lin W B. J. Am. Chem. Soc., 2008, 130(35): 11584.

doi: 10.1021/ja803383k     URL    
[71]
Imaz I, Rubio-Martínez M, García-Fernández L, García F, Ruiz-Molina D, Hernando J, Puntes V, Maspoch D. Chem. Commun., 2010, 46(26): 4737.

doi: 10.1039/c003084h     URL    
[72]
He C B, Lu K D, Liu D M, Lin W B. J. Am. Chem. Soc., 2014, 136(14): 5181.
[73]
Chen Q C, Xu M, Zheng W J, Xu T Y, Deng H, Liu J. ACS Appl. Mater. Interfaces, 2017, 9(8): 6712.

doi: 10.1021/acsami.6b12792     URL    
[74]
Huang C X, Tan W L, Zheng J, Zhu C, Huo J, Yang R H. ACS Appl. Mater. Interfaces, 2019, 11(29): 25740.

doi: 10.1021/acsami.9b08115     URL    
[75]
Zhu W J, Yang S D, Qu C X, Zhu Q L, Chen W L, Li F, Yuan Z Q, Liu Y, You B G, Zhang X N. Int. J. Nanomed., 2017, 12: 3375.

doi: 10.2147/IJN     URL    
[76]
Zhao J, Mi Y, Feng S S. Biomaterials, 2013, 34(13): 3411.

doi: 10.1016/j.biomaterials.2013.01.009     URL    
[77]
Yin T J, Wang L, Yin L F, Zhou J P, Huo M R. Biomaterials, 2015, 61: 10.

doi: 10.1016/j.biomaterials.2015.05.022     URL    
[78]
Liu H M, Qiao C M, Yang J, Weng J, Zhang X. J. Mater. Chem. B, 2014, 2(35): 5910.

doi: 10.1039/C4TB00814F     URL    
[79]
Yin J Y, Lang T Q, Cun D M, Zheng Z, Huang Y, Yin Q, Yu H J, Li Y P. Theranostics, 2017, 7(17): 4204.

doi: 10.7150/thno.21516     URL    
[80]
Sun T M, Du J Z, Yao Y D, Mao C Q, Dou S, Huang S Y, Zhang P Z, Leong K W, Song E W, Wang J. ACS Nano, 2011, 5(2): 1483.

doi: 10.1021/nn103349h     URL    
[81]
Barenholz Y. J. Control. Release, 2012, 160(2): 117.

doi: 10.1016/j.jconrel.2012.03.020     URL    
[82]
Guan J B, Sun J, Sun F L, Lou B, Zhang D, Mashayekhi V, Sadeghi N, Storm G, Mastrobattista E, He Z G. Nanoscale, 2017, 9(26): 9190.

doi: 10.1039/C7NR02663C     URL    
[83]
Li C, Li T Z, Huang L F, Yang M S, Zhu G Y. Chem. Asian J., 2019, 14(9): 1570.

doi: 10.1002/asia.v14.9     URL    
[84]
Zhang C M, Zhang S B, Zhi D F, Zhao Y N, Cui S H, Cui J N. Colloids Surf. A: Physicochem. Eng. Aspects, 2020, 585: 124054.
[85]
Wang Y B, Gao F H, Jiang X W, Zhao X, Wang Y, Kuai Q Y, Nie G J, He M, Pan Y J, Shi W, Ren S P, Yu Q. J. Biomed. Nanotechnol., 2019, 15(5): 966.

doi: 10.1166/jbn.2019.2762     URL    
[86]
Zhao X, Li F, Li Y Y, Wang H, Ren H, Chen J, Nie G J, Hao J H. Biomaterials, 2015, 46: 13.

doi: 10.1016/j.biomaterials.2014.12.028     URL    
[87]
Chen X Y, Zhang Y D, Tang C M, Tian C L, Sun Q, Su Z G, Xue L J, Yin Y F, Ju C Y, Zhang C. Int. J. Pharm., 2017, 5291-2: 102.
[88]
Gao J, Chen H W, Yu Y S, Song J J, Song H, Su X, Li W, Tong X, Qian W Z, Wang H, Dai J X, Guo Y J. Biomaterials, 2013, 34(38): 10084.

doi: 10.1016/j.biomaterials.2013.08.088     URL    
[89]
Mehnert W, Mäder K. Adv. Drug Deliv. Rev., 2012, 64: 83.

doi: 10.1016/j.addr.2012.09.021     URL    
[90]
Yu Y H, Kim E, Park D E, Shim G, Lee S, Kim Y B, Kim C W, Oh Y K. Eur. J. Pharm. Biopharm., 2012, 80(2): 268.

doi: 10.1016/j.ejpb.2011.11.002     URL    
[91]
Bae K H, Lee J Y, Lee S H, Park T G, Nam Y S. Adv. Healthc. Mater., 2013, 2(4): 576.

doi: 10.1002/adhm.v2.4     URL    
[92]
Sun M, Yang C X, Zheng J, Wang M, Chen M W, Le D Q S, Kjems J, Bünger C E. Acta Biomater., 2015, 28: 171.

doi: 10.1016/j.actbio.2015.09.029     URL    
[93]
Kim H O, Kim E, An Y, Choi J, Jang E, Choi E B, Kukreja A, Kim M H, Kang B, Kim D J, Suh J S, Huh Y M, Haam S. Macromol. Biosci., 2013, 13(6): 669.

doi: 10.1002/mabi.201370018     URL    
[94]
Zhang L, Gu F X, Chan J M, Wang A Z, Langer R S, Farokhzad O C. Clin. Pharmacol. Ther., 2008, 83(5): 761.

pmid: 17957183
[95]
Biswas S, Deshpande P P, Navarro G, Dodwadkar N S, Torchilin V P. Biomaterials, 2013, 34(4): 1289.

doi: 10.1016/j.biomaterials.2012.10.024     pmid: 23137395
[96]
Mohammed A F A, Higashi T, Motoyama K, Ohyama A, Onodera R, Khaled K A, Sarhan H A, Hussein A K, ARIMA H. AAPS J., 2019, 21(4): 1.
[97]
Deng Z J, Morton S W, Ben-Akiva E, Dreaden E C, Shopsowitz K E, Hammond P T. ACS Nano, 2013, 7(11): 9571.

doi: 10.1021/nn4047925     URL    
[98]
Labala S, Jose A, Chawla S R, Khan M S, Bhatnagar S, Kulkarni O P, Venuganti V V K. Int. J. Pharm., 2017, 525(2): 407.

doi: 10.1016/j.ijpharm.2017.03.087     URL    
[99]
Yang X Q, Iyer A K, Singh A, Milane L, Choy E, Hornicek F J, Amiji M M, Duan Z F. Pharm. Res., 2015, 32(6): 2097.

doi: 10.1007/s11095-014-1602-1     URL    
[100]
Choi K Y, Silvestre O F, Huang X L, Min K H, Howard G P, Hida N, Jin A J, Carvajal N, Lee S W, Hong J I, Chen X Y. ACS Nano, 2014, 8(5): 4559.

doi: 10.1021/nn500085k     URL    
[101]
Tian G X, Pan R Y, Zhang B, Qu M H, Lian B, Jiang H, Gao Z Q, Wu J L. Front. Pharmacol., 2019, 10: 4.

doi: 10.3389/fphar.2019.00004     URL    
[102]
Zhi F, Dong H, Jia X, Guo W, Lu H, Yang Y, Ju H X, Zhang X, Hu Y,. PLoS ONE, 2013, 8: e60034.
[103]
Gupta B, Ruttala H B, Poudel B K, Pathak S, Regmi S, Gautam M, Poudel K, Sung M H, Ou W, Jin S G, Jeong J H, Ku S K, Choi H G, Yong C S, Kim J O,. ACS Appl. Mater. Interfaces, 2018, 10: 24392.
[104]
Xu F, Ye M L, Zhang Y P, Li W J, Li M T, Wang H Z, Qiu X, Xu Y, Yin J W, Hu Q, Wei W H, Chang Y, Liu L, Zhao Q,. Cancer Sci., 2020, 111: 1528.
[105]
Li J W, Yuan D D, Zheng X J, Zhang X Y, Li X M, Zhang S S. Sci. China Chem., 2020, 63(4): 546.

doi: 10.1007/s11426-019-9673-4     URL    
[106]
Viswanathan V S, Ryan M J, Dhruv H D, Gill S, Eichhoff O M, Seashore-Ludlow B, Kaffenberger S D, Eaton J K, Shimada K, Aguirre A J, Viswanathan S R, Chattopadhyay S, Tamayo P, Yang W S, Rees M G, Chen S X, Boskovic Z V, Javaid S, Huang C, Wu X Y, Tseng Y Y, Roider E M, Gao D, Cleary J M, Wolpin B M, Mesirov J P, Haber D A, Engelman J A, Boehm J S, Kotz J D, Hon C S, Chen Y, Hahn W C, Levesque M P, Doench J G, Berens M E, Shamji A F, Clemons P A, Stockwell B R, Schreiber S L. Nature, 2017, 547(7664): 453.

doi: 10.1038/nature23007     URL    
[107]
Hangauer M J, Viswanathan V S, Ryan M J, Bole D, Eaton J K, Matov A, Galeas J, Dhruv H D, Berens M E, Schreiber S L, McCormick F, McManus M T. Nature, 2017, 551(7679): 247.

doi: 10.1038/nature24297     URL    
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