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Redox-Responsive Dual Chemophotothermal Therapeutic Nanomedicine for Imaging-Guided Combinational Therapy.

ABSTRACT: Chemotherapy is currently the major therapeutic method against cancer. However, chemo drugs are usually lacking in the specificity towards cancer cells over normal cells. In this study, we prepared a novel multifunctional trimeric prodrug by linking the chemo drug camptothecin (CPT) and the exceptional photostable near infrared (NIR) croconaine dye (CR) via a glutathione (GSH)-sensitive disulfide linker. Compared with CPT, our novel trimeric CR-(SS-CPT)2 is more hydrophobic and bulky, making it highly effcient to be encapsulated into biocompatible polymeric nanocarrier. The prodrug underwent rapid drug release specifically in cancer cells with high GSH concentration. The hyperthermia produced by CR upon laser irradiation could further accelerate the break of disulfide bond, which makes the release of CPT even more controllable. We further loaded the CR-(SS-CPT)2 into folate modified lipid-polymer nanoparticles, which demonstrated high in vivo tumor accumulation and retention. The biodistribution of these nanoparticles can be directly monitored in real time via NIR fluorescence and photoacoustic imaging. Under the imaging guided chemo- and photothermal- synergistic therapy, the tumors were completely ablated with no recurrence. The design not only highly enhanced the therapeutic specificity and effeciency of CPT, but also provide a "all in one" nanomedicine for imaging-guided dual modality therapy.

SUBMITTER: Yu F

PROVIDER: S-EPMC6435337 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Redox-Responsive Dual Chemophotothermal Therapeutic Nanomedicine for Imaging-Guided Combinational Therapy.

Yu Fei F Zhang Fuwu F Tang Longguang L Ma Jingwen J Ling Daishun D Chen Xiaoyuan X Sun Xiaolian X

Journal of materials chemistry. B 20180723 33

Chemotherapy is currently the major therapeutic method against cancer. However, chemo drugs are usually lacking in the specificity towards cancer cells over normal cells. In this study, we prepared a novel multifunctional trimeric prodrug by linking the chemo drug camptothecin (CPT) and the exceptional photostable near infrared (NIR) croconaine dye (CR) <i>via</i> a glutathione (GSH)-sensitive disulfide linker. Compared with CPT, our novel trimeric CR-(SS-CPT)<sub>2</sub> is more hydrophobic and ...[more]

PMID: 30931124

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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

Redox-Responsive Dual Chemophotothermal Therapeutic Nanomedicine for Imaging-Guided Combinational Therapy.

Publications

Redox-Responsive Dual Chemophotothermal Therapeutic Nanomedicine for Imaging-Guided Combinational Therapy.

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