Nanotherapeutics demonstrate poor accumulation in the tumor microenvironment due to poor extravasation and penetration into the tumor. Therapeutics such as oligonucleotides, peptides and other biologicals suffer from low systemic half-life and rapid degradation. Albumin-hitchhiking has emerged as an effective strategy to enhance tumor-specific accumulation of various therapeutics. Hitchhiking on serum albumin (SA) have shown to improve biological half-life of various therapeutics including nanocarriers (NCs), biologics, oligonucleotides, vaccines, etc. In addition, passive and active accumulation of SA-riding therapeutics in the tumor, site-specific drug release, and SA-mediated endosomal escape have improved the potential of various anticancer modalities such as chemo-, immune-, vaccine, and gene therapies. In this review, we have discussed the advantages of employing SA-hitchhiking in anticancer therapies. In addition, vaccine strategies employing inherent lymph-nodes accumulating property of albumin have been discussed. We have presented a clinical overview of SA-hitchhiked formulations along with possible bottlenecks for improved clinical outcomes. We have also discussed the role of physiologically based pharmacokinetics (PBPK) modelling for efficient characterization of anti-cancer nanotherapeutics.
Keywords: Albumin hitchhiking; Immunotherapy; Nanocarriers; Oligonucleotides; Peptide; Physiologically based pharmacokinetics; Vaccine.
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