Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Volume 187, Issue -, Pages 24-34Publisher
ELSEVIER
DOI: 10.1016/j.ijbiomac.2021.07.080
Keywords
Human serum albumin; Cancer therapy; Conjugate; Nanoparticle; Fusion protein; Prodrug
Funding
- Chinese Academy of Medical Sci-ences (CAMS) Innovation Fund for Medical Sciences [2016-I2M-3-013, 2019-I2M-1-005]
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Human serum albumin (HSA)-based therapeutics have shown great potential in the development of anticancer agents, with versatile properties that improve pharmacokinetics and reduce toxicity. Different technical platforms have been explored for tumor-oriented therapy, focusing on strategies like enhanced drug delivery and reduced toxicity.
Human serum albumin (HSA)-based therapeutics have attracted tremendous attention in the development of anticancer agents. The versatile properties of HSA make HSA-based therapeutics possess improved pharmacokinetics, extended circulation half-life, enhanced efficacy, reduced toxicity, etc. Generally, the HSA-based therapeutics systems can be divided into four categories, i.e. HSA-drug nanoparticles, HSA-drug conjugates, HSA-binding prodrugs, and HSA-based recombinant fusion proteins: the latter mainly include antibody (domain)- and cytokine- fusion proteins. Advances in this area revealed the advantages of HSA-based systems in the development of tumor site-oriented therapeutics, partly referring to the enhanced penetration and retention (EPR) effect and the intensive macropinocytosis. Accordingly, a variety of technical platforms for the design and preparation of HSA-based therapeutics have been reported. Major strategies and directions for the drug development were discussed; those include (1) Tumor-site oriented drug delivery and enhanced drug retention, (2) Tumor-site prodrug release and activation, (3) Cancer cell bound intensive drug internalization, and (4) Tumor microenvironment (TME) directed immunomodulation. Notably, the multimodal HSA-based approach is promising for the development of tumor-oriented therapeutics for cancer therapy.
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