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Issue 35, 2020
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Rational design of a “dual lock-and-key” supramolecular photosensitizer based on aromatic nucleophilic substitution for specific and enhanced photodynamic therapy

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Abstract

Photosensitizing agents are essential for precise and efficient photodynamic therapy (PDT). However, most of the conventional photosensitizers still suffer from limitations such as aggregation-caused quenching (ACQ) in physiological environments and toxic side-effects on normal tissues during treatment, leading to reduced therapeutic efficacy. Thus, integrating excellent photophysical properties and accurate carcinoma selectivity in a photosensitizer system remains highly desired. Herein, a “dual lock-and-key” supramolecular photosensitizer BIBCl–PAE NPs for specific and enhanced cancer therapy is reported. BIBCl–PAE NPs are constructed by encapsulating a rationally designed glutathione (GSH)-activatable photosensitizer BIBCl in a pH-responsive diblock copolymer. In normal tissues, BIBCl is “locked” in the hydrophobic core of the polymeric micelles due to ACQ. Under the “dual key” activation of low pH and high levels of GSH in a tumor microenvironment, the disassembly of micelles facilitates the reaction of BIBCl with GSH to release water-soluble BIBSG with ideal biocompatibility, enabling the highly efficient PDT. Moreover, benefiting from the Förster resonance energy transfer effect of BIBSG, improved light harvesting ability and 1O2 production are achieved. In vitro and vivo experiments have demonstrated that BIBCl–PAE NPs are effective in targeting and inhibiting carcinoma. BIBCl–PAE NPs show superior anticancer efficiency relative to non-activatable controls.

Graphical abstract: Rational design of a “dual lock-and-key” supramolecular photosensitizer based on aromatic nucleophilic substitution for specific and enhanced photodynamic therapy

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Article information


Submitted
25 Feb 2020
Accepted
21 Aug 2020
First published
25 Aug 2020

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2020,11, 9703-9711
Article type
Edge Article

Rational design of a “dual lock-and-key” supramolecular photosensitizer based on aromatic nucleophilic substitution for specific and enhanced photodynamic therapy

K. Teng, L. Niu, Y. Kang and Q. Yang, Chem. Sci., 2020, 11, 9703
DOI: 10.1039/D0SC01122C

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    [Original citation] - Published by The Royal Society of Chemistry.

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