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双燃料驱动纳米载体在异常细胞间质液中的压力梯度反作用增强药物传递效率。

Pressure-Gradient Counterwork of Dual-Fuel Driven Nanocarriers in Abnormal Interstitial Fluids for Enhancing Drug Delivery Efficiency.

机构信息

Institute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu, Sichuan, 610031, China.

出版信息

Small. 2023 Jun;19(24):e2207252. doi: 10.1002/smll.202207252. Epub 2023 Mar 15.

Abstract

The abnormal pressure in tumor tissue is a significant limitation on the drug delivery efficiency of tumor therapy. This work reports a gradient-driven nanomotor as drug nanocarrier with the pressure-counterworking function. The dual-fuel nanomotors are formed by co-electrospinning of the photosensitive polymers with calcium peroxide (CaO ) and catalase (CAT), followed by ultraviolet (UV) irradiation and bovine serum albumin (BSA) incubation. The UV-responsive cleavage nanomotors can effectively release O molecules at the fractures as a driving force to increase the delivery speed and escape the phagocytosis of macrophage system in normal tissues. Furthermore, CAT catalyzes H O produced by CaO and the tumor interstitial fluids to provide stronger power for the nanomotors. Additionally, according to the analysis of directional motions of the nanomotors, the functional relationship between the rotational diffusion coefficient (D ) and the physiological viscosity is constructed. The dual-fuel nanocarriers enable up to 13.25% of the injected dose (ID)/per gram tissue and significantly improve the penetration in deep tumor. It is of vital importance to design and obtain the adaptive pressure-gradient counterworking nanomotors, which can effectively improve the drug delivery efficiency in vitro and in vivo.

摘要

肿瘤组织中的异常压力是肿瘤治疗药物输送效率的一个重大限制。本工作报道了一种梯度驱动纳米马达作为具有压力对抗功能的药物纳米载体。双燃料纳米马达是通过共静电纺丝光敏聚合物与过氧化钙(CaO)和过氧化氢酶(CAT)形成的,然后进行紫外线(UV)照射和牛血清白蛋白(BSA)孵育。UV 响应性断裂纳米马达可以有效地在断裂处释放 O 分子作为驱动力,以提高输送速度并逃避正常组织中巨噬细胞系统的吞噬作用。此外,CAT 催化 CaO 和肿瘤间质液产生的 H O ,为纳米马达提供更强的动力。此外,根据纳米马达的定向运动分析,构建了旋转扩散系数(D)与生理粘度之间的功能关系。双燃料纳米载体使注射剂量(ID)/每克组织高达 13.25%,并显著提高了深层肿瘤的穿透性。设计和获得自适应压力梯度对抗纳米马达对于有效提高体外和体内的药物输送效率至关重要。

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