摘要
以1-叔丁氧基羰基-2-丙烯酰肼(Boc-AH)、N-(3,4-二羟基苯乙基)丙烯酰胺(DA)和聚乙二醇甲醚丙烯酸酯(mPEGA)为单体,利用可逆加成-断裂链转移聚合法制备了嵌段共聚物聚丙烯酰肼-聚N-(3,4-二羟基苯乙基)丙烯酰胺-聚单甲氧基聚乙二醇丙烯酸酯(PAH-b-PAD-bPmPEGA,缩写为HDP),该共聚物经酚羟基偶联于金纳米棒(GNR)表面,酰肼基团与阿霉素(DOX)中羰基形成酸敏感的腙键从而实现药物装载,构建了光热-化疗联合治疗的纳米体系(HDP-GNR-DOX)。利用紫外-可见(UV-Vis)吸收光谱和溶液颜色变化检测GNR的悬浮稳定性。利用透射电镜、流式细胞术和激光共聚焦显微镜研究了纳米药物被细胞摄取及细胞内分布情况。利用MTT法评估HDP-GNR-DOX介导的光热-化疗联合治疗效果。利用活/死细胞检验方法进一步分析了纳米药物对细胞的杀伤效果。结果表明,该纳米体系载药率高达8.1%,具有优异的光热性能和pH响应性药物释放性能。细胞实验表明,该纳米体系可被人乳腺癌细胞(MCF-7)有效摄取,具有光热-化疗协同杀伤肿瘤细胞的功效。
A triblock copolymer with mussel-inspired adhesive ability, poly(acryl hydrazide)-b-poly(N-(3, 4-dihydroxyphenylethyl) acrylamide)-b-poly(monomethoxypolyethylene glycol acrylate)(PAH-b-PAD-b-PmPEGA,abbreviated as HDP), was designed and synthesized via reversible addition fragmentation chain transfer polymerization process from three monomers, including 1-tert-butcarbonyl-2-acrylhydrazide(Boc-AH), N-(3, 4-dihydroxyphenylethyl)acrylamide(DA) and poly(ethylene glycol) methyl ether methacrylate(mPEGA). The copolymer was used for decorating gold nanorod(GNR) to obtain GNR-based nanocarrier. Chemotherapeutic drug doxorubicin(DOX) was conjugated onto the nanocarrier by an acid-labile hydrazone linkage, resulting in HDP-GNR-DOX nanodrug. The physicochemical properties of the nanocarrier, such as structure, stability, photothermal performance, and pH-responsive drug release, were characterized.Moreover, the in vitro anti-tumor effect of the nanodrug towards breast cancer cells(MCF-7) was evaluated. Results showed that the DOX content of the nanodrug was as high as 8.1% and the nanodrug exhibited excellent photothermal conversion ability, favorable stability and pH-responsive drug release behavior. Importantly, the results of cellular experiments demonstrated that the nanodrug could be effectively internalized by MCF-7. In the case of near infrared irradiation, the nanodrug showed high apoptosis-inducing ability on MCF-7, achieving highly efficient photothermal-chemotherapy of breast cancer.
作者
郭敏
侯光晖
胥伟军
钱军民
GUO Min;HOU Guanghui;XU Weijun;QIAN Junmin(State Key Laboratory for Mechanical Behavior of Materials,Xi’an Jiaotong University,Xi’an 710049,China)
出处
《功能高分子学报》
CAS
CSCD
北大核心
2022年第1期44-53,共10页
Journal of Functional Polymers
基金
国家自然科学基金(82073309)
陕西省重点研发计划(2020SF-033,2020GY-290)。
关键词
嵌段共聚物
金纳米棒
联合治疗
光热-化疗
block copolymer
gold nanorod
combination therapy
photothermal-chemotherapy
