Emerging nanotechnological strategies for delivering bioactive components from botanical drugs and traditional Chinese medicine in atherosclerosis therapy: from formulation to mechanism.

Atherosclerosis (AS), the primary pathological basis of global cardiovascular disease mortality, is undergoing a paradigm shift in treatment strategy, from risk factor management toward precise plaque intervention. Nano-formulations are a major research focus in pharmaceutics. The "nanoization" of traditional Chinese medicine (TCM) has opened new avenues for innovation, not only altering the scale of TCM applications but also expanding their therapeutic scope. TCM nano-formulations can preserve the "multi-target, multi-level" characteristics inherent to TCM therapy while addressing low oral bioavailability and inadequate tissue targeting of active metabolites. These nanoparticles are typically produced by combining extracts or active compounds from botanical drugs or medicinal plants with nanocarriers. Compared with conventional botanical drug preparations, they can markedly improve bioavailability and stability, reduce toxic side effects, and preserve the intrinsic properties of the medicinal components. This article systematically reviews common types of TCM nano-formulations, including nanoemulsions, nanosuspensions, and nanoliposomes, and discusses recent advances in their application to AS. Furthermore, it analyzes bioinspired nano-delivery systems, such as platforms integrating anti-AS peptides, HDL, platelet membranes, or macrophage membranes with natural metabolites possessing anti-inflammatory or antioxidant activities. These systems exert anti-AS effects through mechanisms including reducing cholesterol levels, promoting cholesterol efflux, and driving macrophage repolarization toward an anti-inflammatory phenotype. Their successful application depends on precise control of nanoparticle size and rational delivery-system design. Nanoization not only enhances drug solubility and stability but also improves therapeutic efficacy and reduces toxicity while maintaining the natural pharmacodynamic profile. Future research may focus on developing oral nano-drug delivery systems, the expansion of targeting strategies by leveraging the homing properties of other immune cells to inflammatory sites, the creation of theranostic platforms using natural products or biologics, and employing microfluidic technologies to enable synergistic co-delivery and enhanced efficacy of dual therapeutic agents. These efforts are expected to provide important insights for research and development (R&D) and clinical translation of new therapies for cardiovascular diseases.