多孔碳纳米材料构建抗肿瘤药物靶向传递系统的研究进展

doi:10.15541/jim20200240

无机材料学报 ›› 2021, Vol. 36 ›› Issue (1): 9-24.DOI: 10.15541/jim20200240

所属专题：封面文章；【生物材料】肿瘤治疗

多孔碳纳米材料构建抗肿瘤药物靶向传递系统的研究进展

程晓昆^1,²,张越¹,吕海军¹,刘歆颖²,侯森林³,陈爱兵¹()

^1. 河北科技大学化学与制药工程学院,石家庄 050018
^2. 南非大学非洲可持续性能源发展研究所, 约翰内斯堡 1710, 南非
^3. 河北医科大学第二附属医院胆胰内镜外科, 石家庄 050000

收稿日期:2020-05-06 修回日期:2020-06-04 出版日期:2021-01-20 网络出版日期:2020-07-10
作者简介:程晓昆(1985-), 女, 博士研究生. E-mail: kunkuner007@163.com
基金资助:
国家自然科学基金(21676070);河北省高校百名优秀创新人才支持计划项目(SLRC2017034);北京分子科学国家实验室项目

Porous Carbon Nanomaterials Based Tumor Targeting Drug Delivery System: a Review

CHENG Xiaokun^1,²,ZHANG Yue¹,Lü Haijun¹,LIU Xinying²,HOU Senlin³,CHEN Aibing¹()

^1. College of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang 050018, China
^2. Institute for the Development of Energy for African Sustainability, University of South Africa, Private Bag X6, Johannesburg 1710, South Africa
^3. The Second Hospital of Hebei Medical University, Bilio-Pancreatic Endoscopic Surgery Department, Shijiazhuang 050000, China

Received:2020-05-06 Revised:2020-06-04 Published:2021-01-20 Online:2020-07-10
About author:CHENG Xiaokun (1985-), female, PhD candidate. E-mail: kunkuner007@163.com
Supported by:
National Natural Science Foundation of China(21676070);Hebei One Hundred-Excellent Innovative Talent Program(III)(SLRC2017034);Beijing National Laboratory for Molecular Sciences

摘要/Abstract

摘要：

抗肿瘤药物靶向传递系统是提高传统化疗药物疗效, 并降低其毒副作用的重要手段。以多孔碳纳米材料为药物载体, 根据肿瘤组织微环境特点, 构建抗肿瘤药物靶向传递系统是实现靶向治疗方案的有效方式。本文围绕基于多孔碳纳米材料的抗肿瘤药物靶向传递系统的构建及应用进行综述, 描述了多孔碳纳米材料适宜载药的设计、合成及功能化修饰; 通过理论与实例相结合的方式, 介绍了提高多孔碳纳米材料载药量和实现联合给药的有效策略; 从内源和外源性敏感刺激的角度, 重点分析了多孔碳纳米材料基于肿瘤微环境构建的靶向传递系统的机制和应用; 阐述了多孔碳纳米材料作为抗肿瘤药物载体面临的生物相容性和生物降解性的问题, 并分析了可能的解决途径; 展望了多孔碳纳米材料在构建肿瘤药物靶向传递系统应用中的前景及发展方向, 为研发靶向、可控的抗肿瘤药物传递系统提供了理论依据和例证支持。

关键词: 多孔碳纳米材料, 结构设计, 抗肿瘤, 靶向, 药物传递系统, 综述

Abstract:

Chemotherapy is the main method used for cancer treatment. However, most chemotherapeutic drugs show low selectivity towards tumor cells. When killing tumor cells, chemotherapeutic drugs can also damage normal tissue cells and induce a series of side effects and toxic reactions, such as gastrointestinal reactions, calvities and so on. An effective way to reduce the adverse drug reactions is to construct targeted delivery systems based on the microenvironment properties of tumor tissue. Porous carbon nanomaterials (PCN), with excellent properties such as good structural stability, pores, and easily modified surface, are promising candidate to be used for such strategy. In this paper, the construction and application of the PCN-based targeted antitumor drugs delivery system were reviewed; the structural properties, the design philosophy of PCN suitable for drug loading were summarized; the effective strategies to improve drug loading on PCN for combined drug delivery were discussed both theoretically and experimentally. The mechanism and applications of PCN for tumor microenvironment based targeted delivery system were analyzed from the perspectives of endogenous sensitive stimulations (such as acidity, redox potential and specific enzyme), exogenous sensitive stimulations (such as light and magnetic) and multiple sensitive stimulations (such as double sensitive stimulations, including acidity/redox potential, acidity/magnetic and magnetic/light, and three sensitive stimulation, including acidity/redox potential/light). The biocompatibility and biodegradability of PCN used as anti-tumor drug delivery system was discussed, and the possible solutions were analyzed. The prospects of the application of PCN to be used in tumor drugs were discussed at the end of this review. This review provides theoretical basis and examples towards design and synthesis of porous carbon (PC) materials based anti-tumor drug delivery system, which may help the research and development of targeted and controllable tumor treatment.

Key words: porous carbon nanomaterials, structural design, antitumor, targeting, drug delivery systems, review

中图分类号:

TQ174

程晓昆, 张越, 吕海军, 刘歆颖, 侯森林, 陈爱兵. 多孔碳纳米材料构建抗肿瘤药物靶向传递系统的研究进展[J]. 无机材料学报, 2021, 36(1): 9-24.

CHENG Xiaokun, ZHANG Yue, Lü Haijun, LIU Xinying, HOU Senlin, CHEN Aibing. Porous Carbon Nanomaterials Based Tumor Targeting Drug Delivery System: a Review[J]. Journal of Inorganic Materials, 2021, 36(1): 9-24.

图/表 15

表1 多孔碳纳米材料的制备方法

Table 1 Preparation of porous carbon nanomaterials

Preparation	Basic steps	Ref.
Hard template method	Impregnate the preformed hard template with carbon source, then remove the template after pyrolysis at a high temperature	[29-30]
Soft template method	Through surfactant assembly, the template is removed after pyrolysis at high temperature	[31-33]
Direct pyrolysis method	Direct pyrolysis of carbon precursors, such as MOF, biomass, ionic liquid or polymer	[34-37]
Chemical vapor deposition method	Introducing two or more gaseous carbon precursors into the tubular quartz reactor, carbon materials obtained through pyrolysis	[38-40]

图1 模板法合成多孔碳纳米材料示意图[41]

Fig. 1 Schematic illustration of template method for synthesis of PCN[41] (a) Soft template method; (b) Hard template method

图2 直接热解法制备(a)金属有机骨架热解成碳[52], (b)植物组织制备分级多孔碳[57], (c)苯胺-吡咯共聚物热解成碳[60], (d)嵌段共聚物聚甲基丙烯酸甲酯-苯乙烯热解成碳[61]

Fig. 2 Schematic illustration of direct pyrolysis methods for synthesis of porous carbon nanomaterials (PCN) (a) Preparation of MOF and porous carbon (PC)[58]; (b) Preparation of PC from plant tissue[59]; (c) Preparation of PC from PAN-co-PPy[60]; (d) Preparation of PC from PMMA-co-PS[61]

图3 (a)羧基化的多孔碳球与阿霉素和叶酸偶联的制备, (b)阿霉素在孔道和表面的吸附形式[71]

Fig. 3 (a) Schematic illustration of the preparation of DOX and FA conjugate with f-PCN to form CB-DOX/FA, and (b) the loading of DOX inside the pores and at the surface of functionalized PCN (f-PCN)[71]

图4 多孔碳球装载阿霉素并基于π-π作用进行通道封装[75]

Fig. 4 Schematic preparation of DOX loaded on oxide mesoporous carbon nanospheres (OMCN) and its channel capped by the interaction of π-π[75]

图5 (a) 双孔核壳介孔碳@二氧化硅[81]和(b)分级孔道多孔中空碳球装载阿霉素及小干扰RNA[82]联合给药载体制备方法

Fig. 5 Schematic illustration of preparing combined administration of (a) hierarchical hybrid dual-pore core-shell mesoporous carbon@silica[81] and (b) PHCNs-PEI-PEG for drug and gene co-loading[82] DOX: doxorubicin; PEI; polyethyleneimine; PEG: poly (ethylene glycol); RF: resorcinlo-formaldehyde

表2 多孔碳纳米材料构建抗肿瘤药物靶向传递系统

Table 2 Construction of tumor targeting drug delivery system based on porous carbon nanomaterials

Structure	Response modes	Drugs	＞啊.
Porous carbon sphere	pH	Mitoxantrone HCl	[87]
Porous carbon sphere	pH	Doxorubicin	[26]
Porous carbon sphere	Specific enzyme	Doxorubicin	[91]
Porous carbon derived from ZIF	Specific enzyme	Methylene blue	[35]
Porous carbon sphere	Redox potential	Doxorubicin	[93]
Hollow porous carbon sphere	Near infrared	Doxorubicin	[82]
Porous carbon sphere	Near infrared	Doxorubicin	[98]
Porous carbon sphere coated with Fe₃O₄	Magnetic	Doxorubicin	[102]
Mesoporous carbon sphere	pH-redox potential	Doxorubicin	[104] [105]
Porous carbon sphere	pH-magnetic	Doxorubicin	[106]
Ordered mesoporous carbon sphere	pH-magnetic	Doxorubicin	[107]
Ordered mesoporous carbon spheres coated with Fe₃O₄	Magnetic-near infrared	Doxorubicin	[108]
Porous carbon spheres coated with Au and Fe₃O₄	Magnetic-near infrared	Doxorubicin	[109]
Hollow porous carbon sphere	pH-redox potential-near infrared	Doxorubicin	[110]

图6 ZnO门控多孔碳球的pH响应性控制释放示意图[87]

Fig. 6 Schematic illustration of pH-responsive controlled release of ZnO-gated MCNs[87] MCN: mesoporous carbon nanoparticles

图7 ZIF热解获得的多孔碳球酶敏感响应示意图[35]

Fig. 7 Schematic illustration of enzyme-responsive of porous carbon obtained from ZIF pyrolysis [35]

图8 多孔中空碳球的修饰及光热响应示意图[98]

Fig. 8 Schematic illustration of modified porous hollow carbon spheres and the photothermal therapy[98]

图9 多孔碳包覆Fe3O4纳米粒子并负载阿霉素的制备[102]

Fig. 9 Schematic illustration of MCNs coated Fe3O4 nanoparticles and DOX loaded[102] PCCMNs: porous carbon coated magnetic nanoparticles; DOX: doxorubicin; 1 Oe≈79.62 A/m

图10 制备pH和谷胱甘肽双敏感的多孔碳球示意图[105]

Fig. 10 Schematic preparation of MCN responsive controlled release by pH and glutathione[105] PAA: polyacrylic acid; PEI: polyc (ethyllene glycol); DOX: doxorubicin

图11 利用花状多孔碳球构建pH和磁复合敏感材料[106]

Fig. 11 Schematic illustration of construction of pH and magnetic composite sensitive materials by flower-like porous carbon composite (FPCS)[106] DOX: doxorubicin

图12 磁热、光热能双敏感释放药物传递载体构建示意图[108]

Fig. 12 Schematic illustration of construction drug delivery by pH and magnetic composite sensitive[108] OMCNs: ordered mesoporous carbon nanospheres; MOMCNs: magnetically OMCNs; TMOMCNs: thermo-sensitiuely MOMCNs; SMOMCNs: silane modified MOMCNs; DOX: doxorubicin

图13 肿瘤化疗pH、谷胱甘肽和光热化疗协同刺激反应药物传递系统的合成示意图[110]

Fig. 13 Schematic preparation of stimuli-responsive MHPCNs based drug delivery system for synergistic pH, glutathione and photothermal of tumor chemotherapy[110] MHPCNs: magnetic hollow porous carbon nanoparticles

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多孔碳纳米材料构建抗肿瘤药物靶向传递系统的研究进展

Porous Carbon Nanomaterials Based Tumor Targeting Drug Delivery System: a Review

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