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<p>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&#xa0;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 IC<sub>50</sub> of 2.21 and 5.23&#xa0;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).</p>

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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

  • 期刊论文

  • 发表日期：

    2025年2月21日

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

摘要

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).