Human serum albumin-based doxorubicin prodrug nanoparticles with tumor pH-responsive aggregation-enhanced retention and reduced cardiotoxicity.

Abstract

Doxorubicin (DOX) is a widely-used anticancer drug, but its cardiotoxicity severely hampers its potency in chemotherapy. Herein, human serum albumin (HSA) is engaged as a biocompatible nanocarrier to load a pH-sensitive DOX prodrug, DMDOX, generating HSA-DMDOX nanoparticles via self-assembly driven by hydrophobic interactions. HSA-DMDOX disperses well in a physiological environment (∼40 nm) but aggregates in a tumor acidic microenvironment (pH 6.5, ∼140 nm) owing to the hydrophobicity increase of DMDOX by protonation of carboxylic groups. In vitro anticancer study showed that HSA-DMDOX exhibited enhanced cellular uptake by 4T1 cells and superior cytotoxicity in comparison to HSA-DOX nanoparticles. In vivo study suggested that HSA-DMDOX achieved long blood circulation, aggregation enhanced tumor retention, comparable antitumor efficacy and reduced cardiotoxicity relative to free DOX. Our work presents a facile and effective approach to delivering anthracyclines by HSA-based tumor pH-responsive nanoparticles with aggregation-enhanced tumor retention and reduced toxicity.

• Authors: Boya Zhang, Shiyu Wan, Xinyu Peng, Mingying Zhao, Sai Li, Yuji Pu, Bin He
• Journal: Journal of materials chemistry. B (J Mater Chem B) Vol. 8 Issue 17 Pg. 3939-3948 (05 06 2020) ISSN: 2050-7518 [Electronic] England
• PMID: 32236239 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibiotics, Antineoplastic
• Prodrugs
• Doxorubicin
• Hydrogen Peroxide
• Serum Albumin, Human

Topics

• Animals
• Antibiotics, Antineoplastic (chemical synthesis, chemistry, pharmacology)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Doxorubicin (chemical synthesis, chemistry, pharmacology)
• Drug Screening Assays, Antitumor
• Female
• Humans
• Hydrogen Peroxide (blood)
• Hydrogen-Ion Concentration
• Mammary Neoplasms, Experimental (drug therapy, pathology)
• Mice
• Mice, Mutant Strains
• Mice, Nude
• Molecular Structure
• Nanoparticles (chemistry)
• Particle Size
• Prodrugs (chemical synthesis, chemistry, pharmacology)
• Serum Albumin, Human (chemistry)
• Surface Properties
• Tumor Cells, Cultured