Reactive oxygen species (ROS) are highly overproduced in cancerous tissues, and thus oxidation-responsive nanoparticles (NPs) have emerged as a promising drug carrier for cancer-targeted drug delivery. In this study, we successfully synthesized poly(vanillyl alcohol-co-oxalate) (PVAX) polymer with an excellent ROS-responsive capacity. A well-established emulsion-solvent evaporation method was used to fabricate PVAX-based curcumin (CUR)-loaded NPs (PVAX-NPs) and their counterparts (poly(lactic-co-glycolic acid)-based CUR-loaded NPs, PLGA-NPs). It was found that these NPs had a hydrodynamic particle size of approximately 245 nm, narrow size distribution (polydispersity index less than 0.1), negative zeta potential (around −18 mV), smooth surface appearance, and high drug encapsulation efficiency. Moreover, we found that the CUR release rate of PVAX-NPs was greatly increased in the presence of a hydrogen peroxide-rich environment due to the cleavage of polyoxalate ester bonds in PVAX polymer, resulting in the evenly distribution of CUR within the whole cancer cells. More importantly, PVAX-NPs exhibited much stronger anticancer activities and pro-apoptotic capacities than PLGA-NPs both in vitro and in vivo. These results clearly demonstrate that these ROS-responsive PVAX-NPs can be exploited as a robust anticancer drug delivery platform in chemotherapy.

中文翻译：

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氧化反应性聚合物纳米粒子的有效制备，以有效地递送抗癌药物。

活性氧（ROS）在癌组织中高度过量产生，因此氧化反应性纳米颗粒（NPs）已成为一种有前途的用于癌症靶向药物递送的药物载体。在这项研究中，我们成功地合成了具有出色的ROS响应能力的聚（香草醇-共草酸酯）（PVAX）聚合物。被用来制造基于PVAX姜黄素（CUR）-loaded的NP（PVAX-NPS）和它们的对应的（聚甲行之有效的乳化溶剂挥发法（乳酸-共-乙醇酸）-基于CUR的NP（PLGA-NP）。发现这些NP具有约245nm的流体动力学粒度，窄的粒度分布（多分散性指数小于0.1），负ζ电势（约-18mV），光滑的表面外观和高的药物包封效率。此外，我们发现，在富含过氧化氢的环境中，由于PVAX聚合物中聚草酸酯键的裂解，PVAX-NPs的CUR释放速率大大提高，导致CUR在整个癌细胞中均匀分布。更重要的是，在体外和体内，PVAX-NPs均比PLGA-NPs表现出更强的抗癌活性和促凋亡能力。这些结果清楚地表明，这些ROS反应性PVAX-NP可被用作化学疗法中强大的抗癌药物递送平台。