Improved Control of Triple-Negative Breast Cancer Tumor and Metastasis with a pH-Sensitive Hyaluronic Acid Nanocarrier for Doxorubicin Delivery.

IF 5.4 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Biomaterials Science & Engineering Pub Date : 2025-01-13 Epub Date: 2024-12-28 DOI:10.1021/acsbiomaterials.4c01485

Sisi Liang, Quy Van-Chanh Le, R Dario Arrua, Tyron Turnbull, Ivan Kempson

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Abstract

Polymer based nanoformulations offer substantial prospects for efficacious chemotherapy delivery. Here, we developed a pH-responsive polymeric nanoparticle based on acidosis-triggered breakdown of boronic ester linkers. A biocompatible hyaluronic acid (HA) matrix served as a substrate for carrying a doxorubicin (DOX) prodrug which also possesses natural affinity for CD44⁺ cells. DOX was functionalized with a boronic acid group, which was covalently linked with the HA polymer, resulting in a stable chemical linker at neutral pH. Under acidic conditions, the boronic ester linker is degraded, dissociating DOX. Compared to free DOX, the DOX HA NPs exhibited preferential accumulation in 4T1 cells. In a BALB/c mouse model, DOX HA NPs improved antitumor activity, dramatically improved control of lung metastases, and ultimately led to enhanced survival. The pH-sensitive HA nanocarriers provide a promising approach to enhance therapeutic outcomes and reduce toxicity in chemotherapy.

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用ph敏感透明质酸纳米载体递送阿霉素改善对三阴性乳腺癌肿瘤和转移的控制。

基于聚合物的纳米制剂为有效的化疗递送提供了广阔的前景。在这里，我们开发了一种基于酸中毒触发的硼酯连接物分解的ph响应聚合物纳米颗粒。生物相容性透明质酸（HA）基质作为底物携带阿霉素（DOX）前药，该前药对CD44+细胞也具有天然亲和力。DOX被硼酸基团功能化，与HA聚合物共价连接，在中性ph下形成稳定的化学连接剂。在酸性条件下，硼酯连接剂被降解，解离DOX。与游离DOX相比，DOX HA NPs在4T1细胞中表现出优先积累。在BALB/c小鼠模型中，DOX HA NPs提高了抗肿瘤活性，显著改善了对肺转移的控制，并最终提高了生存率。ph敏感的透明质酸纳米载体为提高化疗效果和降低化疗毒性提供了一种有前途的方法。

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来源期刊

ACS Biomaterials Science & Engineering Materials Science-Biomaterials

CiteScore

10.30

自引率

3.40%

发文量

413

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