Liang Sisi, Le Quy Van-Chanh, Arrua R Dario, Turnbull Tyron, Kempson Ivan
Future Industries Institute, University of South Australia, Mawson Lakes, South Australia 5095, Australia.
Clinical and Health Science, University of South Australia, Adelaide, South Australia 5001, Australia.
ACS Biomater Sci Eng. 2025 Jan 13;11(1):623-633. doi: 10.1021/acsbiomaterials.4c01485. Epub 2024 Dec 28.
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.
基于聚合物的纳米制剂为有效的化疗给药提供了广阔前景。在此，我们基于酸中毒触发的硼酸酯连接体分解开发了一种pH响应性聚合物纳米颗粒。生物相容性透明质酸（HA）基质用作携带阿霉素（DOX）前药的底物，该前药对CD44细胞也具有天然亲和力。DOX用硼酸基团进行功能化，硼酸基团与HA聚合物共价连接，在中性pH下形成稳定的化学连接体。在酸性条件下，硼酸酯连接体降解，使DOX解离。与游离DOX相比，DOX HA纳米颗粒在4T1细胞中表现出优先积累。在BALB/c小鼠模型中，DOX HA纳米颗粒提高了抗肿瘤活性，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HA纳米载体为提高化疗疗效和降低毒性提供了一种有前景的方法。
