Harnessing Folate Receptors: A Comprehensive Review on the Applications of Folate-Adorned Nanocarriers for the Management of Melanoma

The advancement in exclusively tailored therapeutic delivery systems has escalated a great deal of interest in targeted delivery to augment therapeutic efficacy and to lessen adverse effects. The targeted delivery approach promisingly helps to surmount the unmet clinical needs of conventional therapies, including chemoresistance, limited penetration, and side effects. In the case of melanoma, various receptors were overexpressed on the tumor site, among which folate receptor (FR) targeting is considered to be a progressive approach for managing melanoma. FRs are the macromolecules of the glycosyl phosphatidylinositol-attached protein that possess globular assembly with a greater affinity toward specific ligands. So, the functional ligands can be utilized to design targeted nanocarriers (NCs) that can effectively bind to overexpressed FRs. Hence, folate-adorned NCs (FNCs) offer various benefits such as site-specific targeting, cargo protection, and minimizing toxicity. This review focuses on the insights and implications of FRs, targeting FRs, and mechanisms, challenges, and advantages of FNCs. Further, the applications of various FNCs, such as liposomes, polymeric NCs, albumin nanoparticles, inorganic NCs, liquid crystalline nanoparticles, and nanogels, have been elaborated for melanoma therapy. Likewise, the potential of FNCs in immunotherapy, photodynamic therapy, chemotherapy, gene therapy, photothermal therapy, and tumor imaging has been exhaustively discussed. Furthermore, translational hurdles and potential solutions are discussed in detail. The present review is expected to give thoughtful ideas to researchers, industry stakeholders, and formulation scientists for the efficacious development of FNCs.