Multiarm Nanoconjugates for Cancer Cell-Targeted Delivery of Photosensitizers

Molecular Pharmaceutics
Yan ZhaoXin Ming

Abstract

Photodynamic therapy, a procedure that uses a photosensitizer to enable light therapy selectively at diseased sites, remains underutilized in oncological clinic. To further improve its cancer selectivity, we developed a polymeric nanosystem by conjugating a photosensitizer IRDye 700DX (IR700) and cancer targeting RGD peptide to 8-arm polyethylene glycol (PEG). The resulting nanoconjugates (RGD-8PEG-IR700) exhibited a hydrodynamic size of 6.6 nm with narrow distribution of size. The targeted nanoconjugates showed significantly higher intracellular uptake of IR700 in integrin αvβ3-expressing A375 and SKOV3 cells when compared with nontargeted control 8PEG-IR700, and an excess amount of RGD peptides could abolish this enhancement, indicating a receptor-mediated uptake mechanism for the targeted polymer conjugates. Phototoxicity studies indicated that RGD-8PEG-IR700 produced massive cell killing in A375 cells after photoirradiation with an IC50 value of 57.8 nM for IR700. In contrast, free IR700 and the control 8PEG-IR700 conjugates did not produce any phototoxicity at the concentrations up to 1 μM IR700. Upon photoirradiation, the RGD-8PEG-IR700 could produce sufficient singlet oxygen in the cells and induced cell apoptosis. The s...Continue Reading

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Citations

Mar 17, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Ejaj AhmadSundeep Singh Saluja
Aug 7, 2018·Journal of Controlled Release : Official Journal of the Controlled Release Society·Chengqiong MaoXin Ming
Jan 16, 2021·ACS Biomaterials Science & Engineering·Shaista IlyasSanjay Mathur

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