In this study, we reported pH-responsive microparticles consisting of poly(D,L-lactide-co-glycolide) (PLGA), aminated hyaluronic acid (aHA) conjugated with 2,3-dimethylmaleic anhydride (DMA, as a pH-responsive cleavable molecule) (aHA-DMA), and doxorubicin (DOX, as an antitumor drug) for local tumor treatment. The DOX-loaded microparticles, denoted as PLGA(aHA-DMA)/DOX MPs, were fabricated using the W₁/O/W₂ multi-emulsification method. These PLGA(aHA-DMA)/DOX MPs (~10 μm in diameter) accelerated the rate of DOX release at pH 6.8 due to the acidic pH-responsive cleavage of the DMA moieties followed by electrostatic-repulsion between aHA and DOX. This event caused the structural destabilization and collapse of the MPs, leading to the rapid release of DOX. Consequently, the PLGA(aHA-DMA)/DOX MPs resulted in significant inhibition of tumor growth, demonstrating their ability for acidic tumor-specific treatment.

中文翻译：

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用于局部肿瘤治疗的生物相容性静电排斥微粒的开发

在这项研究中，我们报道了由聚（D,L-丙交酯-共-乙交酯）（PLGA）、胺化透明质酸（aHA）与 2,3-二甲基马来酸酐（DMA，作为 pH 响应可裂解分子）（aHA-DMA）和阿霉素（DOX，作为一种抗肿瘤药物）用于局部肿瘤治疗。加载 DOX 的微粒，表示为 PLGA(aHA-DMA)/DOX MPs，使用 W ₁ /O/W _{2 制造}多乳化法。这些 PLGA(aHA-DMA)/DOX MPs（直径约 10 μm）在 pH 6.8 时加速了 DOX 的释放速率，这是由于 DMA 部分的酸性 pH 响应裂解，随后是 aHA 和 DOX 之间的静电排斥。这一事件导致 MPs 的结构不稳定和崩溃，导致 DOX 的快速释放。因此，PLGA(aHA-DMA)/DOX MPs 显着抑制了肿瘤生长，证明了它们对酸性肿瘤特异性治疗的能力。