Dual-Responsive Methotrexate-Human Serum Albumin Complex-Encapsulated Liposomes for Targeted and Enhanced Atherosclerosis Therapy

Overview

Journal Int J Nanomedicine

Publisher Dove Medical Press

Specialty Biotechnology

Date 2025 Feb 26

PMID 40007906

Authors

Xueqin Wang

Xiaodong Chen

Huawen Ji

Along Han

Chengxi Wu

Jun Jiang

Yu Nie

Chunhong Li

Xiangyu Zhou

Affiliations

Soon will be listed here.

Abstract

Introduction: In plaque sites of atherosclerosis (AS), the physiological barrier caused by the thick fiber cap due to the overmigration of vascular smooth muscle cells (VSMCs) prevents efficient drug delivery to damaged macrophages. How to ensure precise targeted delivery of drugs to plaque sites and their on-demand release to dysfunctional cells under the thick fibrous cap are feasible solutions to enhance AS treatment.

Methods: A small complex of methotrexate (MTX)-human serum albumin (HSA) with strong, thick fibrous cap penetration ability was encapsulated in a cholesterol hemisuccinate (CHEM) prepared pH-sensitive liposome, modifying with ROS-responsive PEG2000-TK-DSPE (PTD), termed PTD/Lipo/MTX-HSA.

Results: PTD/Lipo/MTX-HSA can achieve precise targeting and on-demand release in response to plaques environments of AS. The designed formulation accelerated the release of the small-sized MTX-HSA complex in response to excess ROS and acidic pH conditions, and it better penetrated the macrophage spheroids. Furthermore, it has precise targeting ability in the AS mouse model and can produce good anti-inflammatory efficacy by inhibiting p65 entry into the nucleus turn out inflammatory factor.

Conclusion: Our formulations work with safety in mind, and it also highlights the potential of precisely targeted and on-demand-released dual-responsive smart nanoplatforms as promising therapeutic options to penetrate deeper plaques for the effective treatment of AS.

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