Next-Generation Nanocarrier Systems for Targeted Drug Delivery: Advances in Lipid, Polymeric, Metal-Based, and Green Nanoparticles

Nanocarrier-based drug delivery has evolved from a concept into a clinically proven platform technology, with lipid nanoparticle (LNP)- based messenger RNA vaccine delivery systems and a wide array of polymeric and metallic nanomedicines as just a few examples. The review aims to be a synthesis of recent advances in the four main classes of nanocarriers: lipid-based (liposomes, solid lipid nanoparticles, nanostructured lipid carriers, and ionizable-lipid LNPs); polymeric (poly (lactic-co-glycolic acid), chitosan, polymeric micelles and dendrimers); metal-based (gold and iron oxide nanoparticles); and green-synthesised nanoparticles (via plants, algae and microbes). For each class, the review discusses synthesis strategies, targeting mechanisms (passive enhanced permeability and retention versus active ligandmediated targeting), and representative preclinical and clinical applications. It compares these approaches with other systems to highlight trade-offs in biocompatibility, payload flexibility, targeting accuracy, and manufacturing scalability. The review discusses key translational obstacles in depth, including interpatient EPR heterogeneity, reproducibility of green-synthesis batches, and gaps in regulatory standardisation, as well as novel solutions such as stimuli-responsive design, microfluidic manufacturing, and image-guided dosing. Based on the overall picture emerging from the review, the future of targeted therapeutics depends on nanocarriers that can adapt to the tumour/tissue microenvironment, with a stronger mechanistic understanding of the tumour/tissue environment.