HASc-responsive dual-drug nano-particles for co-delivery of Pt(II) and BAI for combination therapy of tumors

IF 4.5 3区工程技术 Q1 CHEMISTRY, APPLIED

Reactive & Functional Polymers Pub Date : 2025-01-13 DOI:10.1016/j.reactfunctpolym.2025.106165

Yifan Zhao , Tong Qiu , Chige Zhuang , Dan Li , Zimin Wan , Hua Zheng , Xueqiong Zhang

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引用次数: 0

Abstract

In this study, ascorbic acid (HASc)-responsive nano-particles were designed to co-deliver the ferroptosis inducer Baicalin (BAI) and the chemotherapeutic drug cisplatin (Pt(II)) to tumor sites, aiming for a synergistic effect of chemotherapy(CT) and ferroptosis. Using CMCS as the carrier, the small-molecule pro-drug cis-Pt(IV)-COOH was grafted onto the carrier to create an amphiphilic polymer pro-drug. Single-drug nano-particles M(Pt) and dual-drug nano-particles M(BAI/Pt) were obtained by ultrasonically self-assembling BAI encapsulated in hydrophobic cores. The M(BAI/Pt) exhibited an average diameter of 211.37

\pm

3.01 nm, a polydispersity index (PDI) of 0.196

\pm

0.015, and a surface charge of −14.93

\pm

0.72 mV, demonstrating excellent stability. Given that cis-Pt(IV)-COOH is sensitive to HASc, the nanoparticles could quickly release Pt(II) with 83.22 % efficiency in simulated tumor cells. Meanwhile, the nanoparticles disintegrated and released BAI with 84.35 % efficiency as well. BAI can induce the accumulation of lipid peroxides by down-regulating GPX4, while Pt(II) contributes to iron ion accumulation. The combined treatment strategy aims to achieve an effective synergistic approach between chemotherapy and ferroptosis. In vitro toxicity studies indicated that the M(BAI/Pt₁_–₁) exhibited significant cytotoxicity, synergistic impact (CI = 0.94) and strong selectivity (SI = 1.60) against 4 T1 cells. Mitochondrial membrane potential assessments and intracellular ROS and MDA analyses indicated that the M(BAI/Pt₁_–₁) generated substantial ROS, causing mitochondrial structural damage and lipid peroxidation in 4 T1 cells. The M(BAI/Pt₁_–₁) induced ferroptosis in 4 T1 cells by downregulating GPX4 expression and decreasing GSH levels, ultimately inhibiting in vitro tumor cell proliferation effectively. Consequently, these nano-particles provide fresh strategy to cancer treatment by combining chemotherapy with ferroptosis.

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来源期刊

Reactive & Functional Polymers 工程技术-高分子科学

CiteScore

8.90

自引率

5.90%

发文量

259

审稿时长

27 days

期刊介绍： Reactive & Functional Polymers provides a forum to disseminate original ideas, concepts and developments in the science and technology of polymers with functional groups, which impart specific chemical reactivity or physical, chemical, structural, biological, and pharmacological functionality. The scope covers organic polymers, acting for instance as reagents, catalysts, templates, ion-exchangers, selective sorbents, chelating or antimicrobial agents, drug carriers, sensors, membranes, and hydrogels. This also includes reactive cross-linkable prepolymers and high-performance thermosetting polymers, natural or degradable polymers, conducting polymers, and porous polymers. Original research articles must contain thorough molecular and material characterization data on synthesis of the above polymers in combination with their applications. Applications include but are not limited to catalysis, water or effluent treatment, separations and recovery, electronics and information storage, energy conversion, encapsulation, or adhesion.