Synthesis and study of amorphous calcium phosphate dual-targeted drug-carrying platforms

Atherosclerosis (AS) has emerged as a significant worldwide health challenge, necessitating the development of a drug-loading platform to achieve precise delivery of anti-AS therapeutics to lesion sites, thereby mitigating its impact. Given the mildly acidic microenvironment and the abundance of activated macrophages overexpressing scavenger receptor class A (SR-A) at AS lesions, we fabricated a pH-responsive, SR-A-targeting multifunctional drug-loading platform (dextran sulfate-heparin/amorphous calcium phosphate, DS-HEP/ACP) <i>via</i> the coprecipitation method. This design enables efficient delivery of the platform to AS plaques with minimal drug loss during systemic circulation. In this study, we characterized the fundamental properties and biological performance of the synthesized DS-HEP/ACP platform and evaluated the anti-AS efficacy of the atorvastatin calcium (AT)-loaded DS-HEP/ACP@AT system <i>in vitro</i>. <i>In vitro</i> drug release results demonstrated that the platform exhibited superior controlled drug release properties, prolonged drug circulation under physiological conditions, while releasing the drug in the weakly acidic microenvironment of AS. Cellular uptake experiments revealed that the modification of the carrier with DS enabled the drug-loading platform to demonstrate efficient uptake through SR-A receptor-specific mechanisms in stimulated macrophages, achieved <i>via</i> specific receptor-mediated targeting strategies. In anti-AS evaluations, the DS-HEP/ACP@AT system demonstrated anti-inflammatory and lipid-lowering effects <i>in vitro</i>, outperforming monotherapy by combining AT-driven lipid reduction with the platform's intrinsic ability to block phagocytosis of oxidized low-density lipoprotein (Ox-LDL) by macrophages. This dual-targeting AS drug-loading platform achieved precise drug delivery, controlled drug release, and enhanced anti-AS efficacy. In summary, our study validates the DS-HEP/ACP@AT system as a promising candidate for AS therapy.