EGFR-Targeted Nanobody Functionalized Polymeric Micelles Loaded with mTHPC for Selective Photodynamic Therapy.

Molecular Pharmaceutics
Yanna LiuSabrina Oliveira

Abstract

meta-Tetra(hydroxyphenyl)chlorin (mTHPC) is one of the most potent second-generation photosensitizers, clinically used for photodynamic therapy (PDT) of head and neck squamous cell carcinomas. However, improvements are still required concerning its present formulation (i.e., Foscan, a solution of mTHPC in ethanol/propylene glycol (40:60 w/w)), as mTHPC has the tendency to aggregate in aqueous media, e.g., biological fluids, and it has limited tumor specificity. In the present study, polymeric micelles with three different diameters (17, 24, and 45 nm) based on benzyl-poly(ε-caprolactone)-b-poly(ethylene glycol) (PCLn-PEG; n = 9, 15, or 23) were prepared with mTHPC loadings ranging from 0.5 to 10 wt % using a film-hydration method as advanced nanoformulations for this photosensitizer. To favor the uptake of the micelles by cancer cells that overexpress the epidermal growth factor receptor (EGFR), the micelles were decorated with an EGFR-targeted nanobody (named EGa1) through maleimide-thiol chemistry. The enhanced binding of the EGFR-targeted micelles at 4 °C to EGFR-overexpressing A431 cells, compared to low-EGFR-expressing HeLa cells, confirmed the specificity of the micelles. In addition, an enhanced uptake of mTHPC-loaded mi...Continue Reading

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Citations

Nov 20, 2020·Journal of Drug Targeting·Jafar SharifiBahman Akbari
Jan 29, 2021·Biomedicines·Su Woong YooEuiheon Chung
Oct 26, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yanna LiuCornelus F van Nostrum
Aug 29, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Reesha KvHsin-Cheng Chiu
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Sep 28, 2021·International Journal of Pharmaceutics·Phuoc Vinh NguyenEmilie Allard-Vannier

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Methods Mentioned

BETA
nuclear magnetic resonance
electrophoresis
xenograft
flow cytometry
confocal microscopy
Fluorescence
xenografts

Software Mentioned

ExPASy ProtParam
GraphPad Prism
ImageJ
Columbus
Empower
Foscan

Related Concepts

Related Feeds

Carcinoma, Squamous Cell

Basal cell carcinoma is a form of malignant skin cancer found on the head and neck regions and has low rates of metastasis. Discover the latest research on basal cell carcinoma here.

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