Host−guest complexation-mediated codelivery of anticancer drug and photosensitizer for cancer photochemotherapy

Author:

Yu Guocan,Zhu Benyue,Shao Li,Zhou Jiong,Saha Manik Lal,Shi Bingbing,Zhang Zibin,Hong Tao,Li ShijunORCID,Chen Xiaoyuan,Stang Peter J.

Abstract

Although platinum-based anticancer drugs prevail in cancer treatment, their clinical applications are limited by the severe side effects as well as their ineffectiveness against drug resistant cancers. A precise combination of photodynamic therapy (PDT) and chemotherapy can synergistically improve the therapeutic outcome and thereby may overcome drug resistance through a multipronged assault. Herein, we employ the well-defined cavity of a discrete organoplatinum(II) metallacage (M) to encapsulate octaethylporphine (OEP), a photosensitizer, forming a dual-functionalized system M⊃OEP that is wrapped into the hydrophobic core of the nanoparticles (MNPs) self-assembled from an amphiphilic diblock copolymer. Using a copper-free click reaction, a targeting ligand is conjugated on the surface of the MNPs, aiming to specifically deliver a chemotherapeutic drug and a photosensitizer to cancer cells. Benefiting from the enhanced permeability and retention effect and active targeting capability, high tumor accumulation of MNPs is achieved, leading to an improved therapeutic outcome and reduced side effects. In vivo studies demonstrate that the combination of chemotherapy and PDT exhibits a superior antitumor performance against a drug-resistant tumor model attributed to their synergistic anticancer efficacy.

Funder

Foundation for the National Institutes of Health

National Natural Science Foundation of China

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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