Peptide-Functionalized Hydrogel Cubes for Active Tumor Cell Targeting

Biomacromolecules
Bing XueEugenia Kharlampieva

Abstract

Conjugation of bioactive targeting molecules to nano- or micrometer-sized drug carriers is a pivotal strategy to improve their therapeutic efficiency. Herein, we developed pH- and redox-sensitive hydrogel particles with a surface-conjugated cancer cell targeting ligand for specific tumor-targeting and controlled release of the anticancer drug doxorubicin. The poly(methacrylic acid) (PMAA) hydrogel cubes of 700 nm and 2 μm with a hepsin-targeting (IPLVVPL) surface peptide are produced through multilayer polymer assembly on sacrificial cubical mesoporous cores. Direct peptide conjugation to the disulfide-stabilized hydrogels through a thiol-amine reaction does not compromise the structural integrity, hydrophilicity, stability in serum, or pH/redox sensitivity but does affect internalization by cancer cells. The cell uptake kinetics and the ultimate extent of internalization are controlled by the cell type and hydrogel size. The peptide modification significantly promotes the uptake of the 700 nm hydrogels by hepsin-positive MCF-7 cells due to ligand-receptor recognition but has a negligible effect on the uptake of 2 μm PMAA hydrogels. The selectivity of 700 nm IPLVVPL-PMAA hydrogel cubes to hepsin-overexpressing tumor cells is fu...Continue Reading

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Citations

Jan 28, 2020·Soft Matter·Sanjoy MondalArun K Nandi
Dec 2, 2020·Materials Science & Engineering. C, Materials for Biological Applications·Shirin MollazadehMostafa Yazdimamaghani
Jul 30, 2019·Langmuir : the ACS Journal of Surfaces and Colloids·Nirzari GuptaEugenia Kharlampieva
Oct 14, 2021·Macromolecular Bioscience·Veronika Kozlovskaya, Eugenia Kharlampieva

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