Self-Crosslinked Albumin Nanoparticles for Targeted Doxorubicin Delivery in Glioblastoma.

Authors

Giuseppina Daniela Naimo, Giuseppe Cirillo, Manuela Curcio, Ludovica Scorzafave, Marco Fiore, Francesca Giordano, Antonella Leggio, Diana Amantea, Fiore Pasquale Nicoletta, Loredana Mauro, Francesca Iemma

Published in

Biomacromolecules. Volume 27. Issue 11. Pages 7625-7639. Nov 09, 2026.

Abstract

We engineered a protein-based nanoplatform exploiting the intrinsic disulfide network of human serum albumin (HSA) to generate self-crosslinked, redox-responsive nanoparticles without synthetic crosslinking agents. Following folic acid conjugation, HSA nanoparticles (f-HNPs) were prepared by desolvation-assisted self-crosslinking and loaded with doxorubicin (DOX) with 88% encapsulation efficiency. The resulting nanoparticles were spherical, with an average diameter of 37 ± 5 nm and PDI of 0.24, and underwent glutathione-triggered destabilization and accelerated drug release under reducing conditions. Empty f-HNPs showed excellent biocompatibility, whereas DOX@f-HNPs enhanced DOX cytotoxicity against U-87MG glioblastoma cells, reducing the IC50 from 0.24 to 0.17 μg mL-1. Competitive inhibition experiments supported folate receptor-mediated uptake and enhanced intracellular drug accumulation. Nanoparticle-mediated delivery increased oxidative stress, mitochondrial depolarization, and G2/M cell-cycle arrest, accompanied by p21 upregulation, Cyclin D1 and Ki67 downregulation, and sustained inhibition of glioblastoma cell proliferation.

PMID:
43002039
Bibliographic data and abstract were imported from PubMed on 09 Nov 2026.

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