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A nuclear targeted dual-photosensitizer for drug-resistant cancer therapy with NIR activated multiple ROS.

ABSTRACT: Photodynamic therapy against cancer, especially multidrug resistant cancer, is limited seriously due to the efflux of photosensitizer molecules by P-glycoprotein, which leads to insufficient production of reactive oxygen species (ROS). For the purpose of abundant ROS generation and effective therapeutic response, herein, we firstly design and fabricate a nuclear targeted dual-photosensitizer for photodynamic therapy against multidrug resistant cancer. Molecule-photosensitizer Ce6 was selected and modified on the surface of core/shell structure nano-photosensitizer upconversion@TiO2 and then nuclear targeted peptides TAT were anchored for nuclear targeting. Through selective doping of rare earth elements Er and Tm, multiple ROS (?OH, O2?-, and 1O2) can be generated for the dual-photosensitizer and realize their functions synergistically using a single 980 nm NIR excitation. The nano-sized photosensitizer accompanied with nuclear targeting can effectively generate multiple ROS in the nucleus regardless of P-glycoprotein and directly break DNA double strands, which is considered as the most direct and serious lesion type for cytotoxic effects. Therefore, enhanced photodynamic therapy can be achieved against multidrug resistant cancer. In vitro and in vivo studies confirmed the excellent therapeutic effect of the dual-photosensitizer against cancer cells and drug-resistant cancer cells, as well as xenograft tumor models.

SUBMITTER: Yu Z

PROVIDER: S-EPMC6013803 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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A nuclear targeted dual-photosensitizer for drug-resistant cancer therapy with NIR activated multiple ROS.

Yu Zhengze Z Pan Wei W Li Na N Tang Bo B

Chemical science 20160311 7

Photodynamic therapy against cancer, especially multidrug resistant cancer, is limited seriously due to the efflux of photosensitizer molecules by P-glycoprotein, which leads to insufficient production of reactive oxygen species (ROS). For the purpose of abundant ROS generation and effective therapeutic response, herein, we firstly design and fabricate a nuclear targeted dual-photosensitizer for photodynamic therapy against multidrug resistant cancer. Molecule-photosensitizer Ce6 was selected an ...[more]

PMID: 30155070

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Project description:Dual functional drug carrier has been a modern strategy in cancer therapy because it is a platform to elicit additive and synergistic effects through combination therapy. Photo-activated external stimuli such as reactive oxygen species (ROS) also ensure adequate drug delivery in a precise temporal and spatial manner. However, current ROS-responsive drug delivery systems usually require tedious synthetic procedures. A facile one-pot approach has been reported herein, to obtain self-assembled polymeric nanocarriers (NCs) for simultaneous paclitaxel (PTX)- and Rose Bengal (RB)-loading to achieve combined chemo-photodynamic therapy and controlled drug release in responsive to a light-induced ROS stimulus. To encapsulate these hydrophobic and hydrophilic drugs, chitosan (CTS), branched polyethylenimine (bPEI) and polyvinyl alcohol (PVA) were selected and fabricated into nanoblended matrices through an oil-in-water emulsion method. The amphiphilic properties of CTS permit simultaneous entrapment of PTX and RB, while the encapsulation efficiency of RB was further improved by increasing the amount of short-chain bPEI. During the one-step assembly process, bovine serum albumin (BSA) was also added to condense the cationic tripolymer mixtures into more stable nanocarriers (BNCs). Hyaluronic acid (HA) was subsequently grafted onto the surface of BNCs through electrostatic interaction, leading to the formation of HA-BSA/CTS/PVA/bPEI-blended nanocarriers (HBNCs) to achieve an efficient prostate-cancer-cell uptake. Importantly, in response to external light irradiation, HBNCs become destabilized owing to the RB-mediated photodynamic action. It allows an on-demand dual-payload release to evoke a simultaneous photodynamic and chemo treatment for cancer cell eradication. Thus, HBNCs present a new promising approach that exhibits a specific vulnerability to RB-induced photosensitization. The consequent dual-cargo release is also expected to successfully combat cancer through a synergistic anti-tumor effect.

Dataset Information

A nuclear targeted dual-photosensitizer for drug-resistant cancer therapy with NIR activated multiple ROS.

Publications

A nuclear targeted dual-photosensitizer for drug-resistant cancer therapy with NIR activated multiple ROS.

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