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Turkish Journal of Biology

JING LU

Abstract

Shell-sheddable nanoparticles, composed of amphiphilic blockpolymers, have emerged as an attractive vehicle for the site-specific delivery of therapeutic agents. In this study, pH-responsive sheddable copolymers bearing an orthoester linker were synthesized via the ring-opening polymerization between γ-benzyl-L-glutamate N-carboxyanhydride and orthoester-bearing poly (ethylene glycol) macroinitiator (PEG-pH-NH2). The obtained poly (ethylene glycol)-b-poly(γ-benzyl-L-glutamate) (PEG-PBLG) could form stable nanoparticles in aqueous solutions due to the amphiphilic nature of the block copolymers. The PEG-PBLG-based nanoparticle exhibited good stability in physiological conditions (pH 7.4), whereas the nanoparticle was disassembled under acidic conditions (pH 5.0). The nanoparticles could encapsulate a photosensitizer, protophorphyrin IX (PpIX), and deliver it into acidic environments. According to optical imaging test, it was found that quenched fluorescence signal of PpIX highly recovered under acidic conditions. Acid-responsive sheddable nanoparticles rapidly release the PpIX when they are incubated under acidic conditions (pH 5.0), and the PpIX release was remarkably reduced in physiological buffer (pH 7.4). In vitro cytotoxicity test showed that cells treated with pH-responsive sheddable nanoparticle became highly phototoxic upon irradiation. Microscopic observation demonstrated that PpIX-loaded nanoparticle rapidly degraded at the endosome of SCC7 cancer cells, which enabled PpIX release into the cancer cells. These results suggest that pH-responsive sheddable are a promising carrier for photodynamic agents.

DOI

10.55730/1300-0152.2643

Keywords

pH-responsive nanoparticles, protophorphyrin IX, sheddable nanocarriers, phototoxicity

First Page

84

Last Page

93

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