Enhanced Antitumor Effects of Epidermal Growth Factor Receptor Targetable Cetuximab-Conjugated Polymeric Micelles for Photodynamic Therapy

Nanomaterials
Ming-Hsiang ChangPing-Shan Lai

Abstract

Nanocarrier-based delivery systems are promising strategies for enhanced therapeutic efficacy and safety of toxic drugs. Photodynamic therapy (PDT)-a light-triggered chemical reaction that generates localized tissue damage for disease treatments-usually has side effects, and thus patients receiving photosensitizers should be kept away from direct light to avoid skin phototoxicity. In this study, a clinically therapeutic antibody cetuximab (C225) was conjugated to the surface of methoxy poly(ethylene glycol)-b-poly(lactide) (mPEG-b-PLA) micelles via thiol-maleimide coupling to allow tumor-targetable chlorin e6 (Ce6) delivery. Our results demonstrate that more C225-conjugated Ce6-loaded polymeric micelles (C225-Ce6/PM) were selectively taken up than Ce6/PM or IgG conjugated Ce6/PM by epidermal growth factor receptor (EGFR)-overexpressing A431 cells observed by confocal laser scanning microscopy (CLSM), thereby decreasing the IC50value of Ce6-mediated PDT from 0.42 to 0.173 μM. No significant differences were observed in cellular uptake study or IC50value between C225-Ce6/PM and Ce6/PM groups in lower EGFR expression HT-29 cells. For antitumor study, the tumor volumes in the C225-Ce6/PM-PDT group (percentage of tumor growth inhibi...Continue Reading

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Citations

Jan 17, 2019·Organic & Biomolecular Chemistry·Sara R G FernandesJoão P C Tomé
Jan 3, 2020·Photochemistry and Photobiology·Aaron J SorrinImran Rizvi
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Nov 15, 2020·International Journal of Pharmaceutics·Elias da Silva SantosJosimar O Eloy

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Methods Mentioned

BETA
electrophoresis
gel filtration
dynamic light scattering
xenograft
NMR
transmission electron microscopy
Protein Assay

Software Mentioned

SPSS

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