Wang Jian, Yu Nianhui, Tang Yunpeng, Cheng Yingsheng, Li Hui
Department of Radiology, Sixth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200231, China.
Pharmaceuticals (Basel). 2024 Dec 10;17(12):1666. doi: 10.3390/ph17121666.
Albumin-bound paclitaxel (nab-PTX) nanoparticles have been proven effective in treating advanced pancreatic cancer. However, the clinical application of nab-PTX nanoparticles is often associated with suboptimal outcomes and severe side effects due to its non-specific distribution and rapid clearance. This study aims to develop a novel nanoplatform that integrates sonodynamic therapy (SDT) and chemotherapy to enhance treatment efficacy and reduce systemic side effects. Bovine serum albumin (BSA) was conjugated with chlorin e6 and paclitaxel (PTX) to form stable nanoparticles (NPs). These NPs were then incorporated into a biodegradable poly(lactic--glycolic acid)--polyethylene glycol--poly(lactic--glycolic acid) hydrogel for targeted drug delivery. The system's stability and drug release profile were analyzed, followed by in vitro studies to evaluate cellular uptake and cancer cell killing efficacy. In vivo evaluation was performed using pancreatic cancer xenograft models, with intratumoral injection of the drug-loaded hydrogel. The developed hydrogel system demonstrated enhanced stability and sustained release of PTX. In vitro analyses revealed significant cellular uptake and synergistic cancer cell killing effects through combined SDT and chemotherapy. In vivo studies showed prolonged intratumoral retention of the drug and remarkable inhibition of tumor growth. This novel nanoplatform offers a promising approach for improving pancreatic cancer treatment by enhancing intratumoral drug retention and minimizing systemic side effects. The synergistic effects of SDT and chemotherapy demonstrate the potential of this strategy in achieving better therapeutic outcomes.
白蛋白结合型紫杉醇（纳米白蛋白紫杉醇，nab-PTX）纳米粒已被证明对晚期胰腺癌有效。然而，由于其非特异性分布和快速清除，nab-PTX纳米粒的临床应用往往伴随着不理想的治疗效果和严重的副作用。本研究旨在开发一种新型纳米平台，将声动力疗法（SDT）与化疗相结合，以提高治疗效果并减少全身副作用。将牛血清白蛋白（BSA）与氯e6和紫杉醇（PTX）偶联，形成稳定的纳米粒（NPs）。然后将这些纳米粒掺入可生物降解的聚（乳酸-乙醇酸）-聚乙二醇-聚（乳酸-乙醇酸）水凝胶中，用于靶向给药。分析了该系统的稳定性和药物释放曲线，随后进行体外研究，以评估细胞摄取和癌细胞杀伤效果。使用胰腺癌异种移植模型进行体内评估，瘤内注射载药水凝胶。所开发的水凝胶系统显示出增强的稳定性和PTX的持续释放。体外分析显示，通过联合SDT和化疗，细胞摄取显著增加，癌细胞杀伤具有协同作用。体内研究表明，药物在肿瘤内的滞留时间延长，肿瘤生长受到显著抑制。这种新型纳米平台通过增强肿瘤内药物滞留和最小化全身副作用，为改善胰腺癌治疗提供了一种有前景的方法。SDT和化疗的协同作用证明了该策略在实现更好治疗效果方面的潜力。
