Engineering of Dual-drug Delivery of Oxaliplatin and Cabazitaxel Using Chitosan-PNIPAM Clacked Metal-organic Frameworks: A Path to Precision of pH/thermo Responsive Tactic to Liver cancer

IF 4.7 3区工程技术 Q2 ENGINEERING, ENVIRONMENTAL

Journal of Polymers and the Environment Pub Date : 2025-02-21 DOI:10.1007/s10924-025-03510-x

Conghuan Shen, Jianhua Li, Quanbao Zhang, Yifeng Tao, Ruidong Li, Zhenyu Ma, Zhengxin Wang

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引用次数: 0

Abstract

A pH/thermo-responsive nanoframeworks has been engineered using ZIF-8 decorated with the chitosan (C)-poly(N-isopropylacrylamide) (C-PNIPAM) for the co-delivery of oxaliplatin (OXP) and cabazitaxel (CTX) in liver cancer cells. The chitosan PNIPAM nanoparticles (CPNPs) exhibited particle diameters of 205 nm and a surface charge of + 28 mV. The CTX and OXP loading contents in the CPNPs were 12.10% and 54.49%. NPs exhibited a pH-and thermo-responsive drug release, characterized by a continuous and extended-release. The anticancer activity demonstrated a notable synergistic effect of OXP@ZIF-8/CTX@CPNPs, resulting in HepG2 and Bel7402 cells IC₅₀ of 2.21 and 5.23 µg/mL. The resultant NPs were lower cytotoxic than OXP and CTX on non-cancerous NIH3T3 cell lines. OXP@ZIF-8/CTX@CPNPs shows enhanced cellular uptake in HepG2 cells. The apoptotic mode of cell death in OXP@ZIF-8/CTX@CPNPs treated cells was indicated by acridine orange/propidium iodide (AO/PI) staining techniques. 4′, 6-diamidino-2-phenylindole (DAPI) staining also confirmed nuclear changes such as fragmentation and condensation. Annexin V-FITC/Propidium iodide (PI) staining with flow cytometry showed that OXP@ZIF-8/CTX@CPNPs improved apoptosis in HepG2 cells. The study validated the superior efficacy of the engineered polymeric drugs integrated with metal-organic nanoframeworks in combinational treatment against liver cancer cell lines, exhibiting reduced adverse effects compared to free anticancer drugs (OXP and CTX).

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壳聚糖- pnipam金属-有机骨架的奥沙利铂和卡巴他赛双药递送工程：通往肝癌pH/热响应策略的精确途径

利用壳聚糖(C)-聚（n -异丙基丙烯酰胺）（C- pnipam）修饰的ZIF-8设计了一种pH/热响应纳米框架，用于在肝癌细胞中共同递送奥沙利铂（OXP）和卡巴他赛（CTX）。壳聚糖PNIPAM纳米颗粒（CPNPs）的粒径为205 nm，表面电荷为+ 28 mV。CPNPs中CTX和OXP的含量分别为12.10%和54.49%。NPs表现出ph和热响应性药物释放，具有连续和缓释的特点。对HepG2和Bel7402细胞的IC50分别为2.21µg/mL和5.23µg/mL。NPs对NIH3T3细胞株的细胞毒性低于OXP和CTX。OXP@ZIF-8/CTX@CPNPs显示HepG2细胞摄取增强。采用吖啶橙/碘化丙啶（AO/PI）染色技术观察OXP@ZIF-8/CTX@CPNPs处理后细胞的凋亡模式。4 '， 6-二氨基-2-苯基吲哚（DAPI）染色也证实了核的变化，如碎裂和缩合。Annexin V-FITC/碘化丙啶（PI）流式细胞术染色显示OXP@ZIF-8/CTX@CPNPs可改善HepG2细胞的凋亡。该研究证实了与金属有机纳米框架结合的工程聚合物药物在联合治疗肝癌细胞系方面的优越疗效，与游离抗癌药物（OXP和CTX）相比，其副作用更小。

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来源期刊

Journal of Polymers and the Environment 工程技术-高分子科学

CiteScore

9.50

自引率

7.50%

发文量

297

审稿时长

9 months

期刊介绍： The Journal of Polymers and the Environment fills the need for an international forum in this diverse and rapidly expanding field. The journal serves a crucial role for the publication of information from a wide range of disciplines and is a central outlet for the publication of high-quality peer-reviewed original papers, review articles and short communications. The journal is intentionally interdisciplinary in regard to contributions and covers the following subjects - polymers, environmentally degradable polymers, and degradation pathways: biological, photochemical, oxidative and hydrolytic; new environmental materials: derived by chemical and biosynthetic routes; environmental blends and composites; developments in processing and reactive processing of environmental polymers; characterization of environmental materials: mechanical, physical, thermal, rheological, morphological, and others; recyclable polymers and plastics recycling environmental testing: in-laboratory simulations, outdoor exposures, and standardization of methodologies; environmental fate: end products and intermediates of biodegradation; microbiology and enzymology of polymer biodegradation; solid-waste management and public legislation specific to environmental polymers; and other related topics.