School of Materials and Chemistry, University of Shanghai for Science and Technology, No. 516 Jungong Road, Shanghai 200093, China.
Department of Gastroenterology, Changhai Hospital, Noval Military Medical University, No. 168 Changhai Road, Shanghai 200433, China.
Colloids Surf B Biointerfaces. 2023 Jan;221:113010. doi: 10.1016/j.colsurfb.2022.113010. Epub 2022 Nov 8.
The degradation of extracellular matrix (ECM) to increase drug permeability is an attractive approach to enhancing pancreatic cancer therapy efficiency. Herein, polypyrrole nanoparticles (PPy NPs) were prepared by a template-guided chemical oxidation method. These PPy NPs with abundant surface pores were used to load the anticancer drug doxorubicin (DOX). In order to intelligently control the DOX release, PPy/DOX NPs were further entrapped with a thermoresponsive ligand, lauric acid (LA), to form PPy-LA/DOX NPs. Bromelain (BL) was then grafted onto the surface of PPy-LA NPs or PPy-LA/DOX NPs through an amidation reaction with the carboxyl group of LA. It was found that the DOX release of PPy-LA/DOX NPs was pH and temperature responsive, reaching a maximum amount of 85.9% within 48 h at pH = 5.4 and 50 °C. Moreover, it was demonstrated that the resultant PLB (PPy-LA-BL) NPs could efficiently hydrolyze the collagen in ECM and enhance the permeability of DOX to the pancreatic tumor. Remarkably, PLB NPs not only featured admirable photothermal conversion but also exhibited obvious photoacoustic imaging capability, which enabled imaging-guided enhanced tumor ablation. This study is anticipated to provide a feasible strategy to improve the permeability of nanoparticles to tumors.
细胞外基质（ECM）的降解以增加药物通透性是提高胰腺癌治疗效率的一种有吸引力的方法。在此，通过模板引导的化学氧化法制备了聚吡咯纳米粒子（PPy NPs）。这些具有丰富表面孔的 PPy NPs 被用于负载抗癌药物阿霉素（DOX）。为了智能控制 DOX 的释放，将 PPy/DOX NPs 进一步用热敏配体月桂酸（LA）包封，形成 PPy-LA/DOX NPs。然后通过与 LA 的羧基进行酰胺化反应，将菠萝蛋白酶（BL）接枝到 PPy-LA NPs 或 PPy-LA/DOX NPs 的表面上。研究发现，PPy-LA/DOX NPs 的 DOX 释放具有 pH 和温度响应性，在 pH = 5.4 和 50°C 下 48 小时内达到最大释放量 85.9%。此外，结果表明，所得的 PLB（PPy-LA-BL） NPs 可以有效地水解 ECM 中的胶原蛋白并增强 DOX 向胰腺肿瘤的通透性。值得注意的是，PLB NPs 不仅具有令人钦佩的光热转换性能，而且还表现出明显的光声成像能力，这使得能够进行成像引导的增强肿瘤消融。这项研究有望为提高纳米粒子对肿瘤的通透性提供一种可行的策略。
