Albumin is a reliable drug-delivering molecule: Highlighting points in cancer therapy

As the most abundant protein in the blood, albumin binds and transports hydrophilic, hydrophobic, and lipophilic molecules required for the growth and development of cells and tissues. Due to the surface location of charged groups and the inner hydrophobic site, it transports proteins, peptides, amino acids, fatty acids, nutrients, and other biomolecules. It is a multi-domain protein involved in various functions of the blood, including the contribution to oncotic pressure. Because of its unique sequence and structure, albumin can be efficiently utilized to develop drug delivery systems against various diseases, including cancer. As a protein, rich in both negative and positive charges on the surface, it attracts great attention in the drug delivery discipline. Inner hydrophobic sites were proven to be an efficient location for delivering hydrophobic and lipophilic drugs. Albumin binding domains, widely distributed among receptors and matricellular molecules, ease its penetration into cells. A high ratio of cysteine provides stability to the molecule and causes thiol-disulfide interactions, which play an essential role in drug release. In this work, we highlighted several points of albumin nature as a drug-carrying molecule regarding biochemical and physical properties: self-assembling, formation of covalent bonds, formation of in situ albumin corona, etc. Research publications were searched in the NCBI database by various keywords related to sections/subsections to review the related topic. Tens of research works have been dedicated to enhancing the therapeutic efficacy of anticancer drugs using albumin in the last two decades and contributed to clarifying the mechanistic action of albumin. We discussed its mechanisms of action in drug delivery in the first section. In another section, we reviewed the enhanced antitumor/anticancer efficacies of those fabricated DDSs in terms of albumin contribution. The results of in vitro and in vivo experiments were merged into that section consisting of subsections of DDSs of individual anticancer means. Clinical trials of three drugs were reviewed as a separate section. The approaches used to enhance the efficacy of albumin-based DDSs were reviewed in the last section. The final section is devoted to strategies that could significantly improve albumin efficacy in cancer drug delivery.