Bio-based nanomaterials for targeted drug delivery in myocardial fibrosis

Myocardial fibrosis, characterized by excessive extracellular matrix deposition and stiffening of cardiac tissue, is a critical pathological process in heart failure and other cardiovascular diseases. Traditional pharmacological treatments offer limited efficacy in reversing fibrosis and often result in systemic side effects due to poor targeting. Bio-based nanocarriers, derived from natural polymers such as chitosan, cellulose, gelatin, lignin, and alginate, have emerged as promising vehicles for the targeted delivery of anti-fibrotic, anti-inflammatory, and antioxidant therapeutics. These materials exhibit excellent biocompatibility, biodegradability, and the capacity for surface functionalization, enabling precise delivery to fibrotic myocardial regions. This review explores the mechanisms of fibroblast activation and signaling pathways involved in cardiac fibrosis, including TGF-β/Smad and angiotensin II-mediated oxidative stress. It further discusses the classification, physicochemical properties, and functionalization strategies of bio-based nanomaterials tailored for cardiac applications. Special emphasis is placed on passive and active targeting, stimuli-responsive drug release systems (e.g., ROS- or enzyme-triggered), and intracellular delivery mechanisms. Preclinical studies demonstrate that these nanocarriers can reduce collagen deposition, mitigate inflammation, and improve cardiac function. Despite these advances, challenges remain regarding pharmacokinetics, immunogenicity, and manufacturing scalability. The integration of emerging technologies such as CRISPR/Cas9, 3D bioprinting, and exosome-based delivery systems offers new opportunities for clinical translation. Overall, bio-based nanocarriers represent a sustainable and highly adaptable platform for precision therapy in myocardial fibrosis, with significant potential to improve patient outcomes in the future.