Department of Child Health Care, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China.
Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, China.
Molecules. 2023 May 31;28(11):4461. doi: 10.3390/molecules28114461.
Chemotherapy is currently one of the most widely used treatments for cancer. However, traditional chemotherapy drugs normally have poor tumor selectivity, leading to insufficient accumulation at the tumor site and high systemic cytotoxicity. To address this issue, we designed and prepared a boronic acid/ester-based pH-responsive nano-drug delivery system that targets the acidic microenvironment of tumors. We synthesized hydrophobic polyesters with multiple pendent phenylboronic acid groups (PBA-PAL) and hydrophilic PEGs terminated with dopamine (mPEG-DA). These two types of polymers formed amphiphilic structures through phenylboronic ester linkages, which self-assembled to form stable PTX-loaded nanoparticles (PTX/PBA NPs) using the nanoprecipitation method. The resulting PTX/PBA NPs demonstrated excellent drug encapsulation efficiency and pH-triggered drug-release capacity. In vitro and in vivo evaluations of the anticancer activity of PTX/PBA NPs showed that they improved the pharmacokinetics of drugs and exhibited high anticancer activity while with low systemic toxicity. This novel phenylboronic acid/ester-based pH-responsive nano-drug delivery system can enhance the therapeutic effect of anticancer drugs and may have high potential for clinical transformations.
化疗是目前治疗癌症最广泛应用的方法之一。然而，传统的化疗药物通常对肿瘤的选择性差，导致在肿瘤部位的积累不足和全身细胞毒性高。为了解决这个问题，我们设计并制备了一种基于硼酸/酯的 pH 响应性纳米药物传递系统，该系统靶向肿瘤的酸性微环境。我们合成了具有多个苯硼酸基团（PBA-PAL）的疏水聚酯和末端带有多巴胺的亲水 PEG（mPEG-DA）。这两种聚合物通过苯硼酸酯键形成两亲性结构，然后通过纳米沉淀法自组装形成稳定的载紫杉醇纳米颗粒（PTX/PBA NPs）。所得的 PTX/PBA NPs 表现出优异的药物包封效率和 pH 触发的药物释放能力。PTX/PBA NPs 的体外和体内抗癌活性评价表明，它们改善了药物的药代动力学，表现出高抗癌活性，同时具有低全身毒性。这种新型基于硼酸/酯的 pH 响应性纳米药物传递系统可以增强抗癌药物的治疗效果，可能具有很高的临床转化潜力。
