Transferrin-guided liposomal nanocarriers: A strategy for targeted cancer treatment

Cancer, characterized by uncontrolled cell proliferation and aberrant vascularization, remains a major challenge in clinical therapeutics. While chemotherapy is a cornerstone of cancer treatment, its effectiveness is often limited by systemic toxicity and lack of tissue specificity, which constrain the achievable therapeutic doses. When compared to traditional formulations, targeted drug delivery systems employing nanoparticles have demonstrated up to ten times greater bioavailability and three to five times higher drug accumulation in tumor tissues. Nanoparticles (NPs) offer versatile and customizable platforms that improve the solubility, permeability, and bioavailability of therapeutic agents. In addition, NPs exhibit favorable pharmacokinetic properties, enable sustained and controlled drug release, and allow selective targeting of specific cells, tissues, or organs-collectively enhancing the therapeutic efficacy of conventional drugs. Also, by lowering systemic toxicity, nanocarriers enable 50-70 % dosage reductions in chemotherapeutic drugs without sacrificing effectiveness. This review highlights recent advances in nanotechnology-driven strategies to overcome these limitations, with a particular focus on transferrin (Tf) receptor-mediated targeting. It begins by discussing the biological rationale for Tf-targeted drug delivery and the advantages of liposomal formulations in oncology, particularly describing their use in treating brain cancer, liver cancer, lung cancer, ovarian cancer, breast cancer, bone cancer, gastric cancer, and prostate cancer. Subsequently, it explores various methods for the preparation of Tf-engineered liposomes, ranging from conventional techniques to advanced drug encapsulation strategies to solve the problems that arises when transferrin is used alone like BBB penetration, Drug resistance. Finally, the review provides a comprehensive analysis of preclinical and clinical studies evaluating the efficacy and safety of Tf-functionalized liposomes in cancer therapy.