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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.

Project description:BackgroundConventional chemotherapy has poor efficacy in triple-negative breast cancer (TNBC) which is highly heterogeneous and aggressive. Imaging-guided therapy is usually combined with diverse treatment modalities, could realize the integration of diagnosis and treatments. Therefore, the primary challenge for combinational therapy is designing proper delivery systems to accomplish multiple synergistic effects.ResultsHerein, a facile nanoplatform was manufactured to fulfill the all-in-one approaches for TNBC combinational therapy. Fe3+-based metal-phenolic networks (MPNs) with bovine serum albumin (BSA) modification served as drug delivery carriers to encapsulate bleomycin (BLM), forming BFE@BSA NPs. The self-assembly mechanism, pH-responsive drug release behavior, and other physicochemical properties of this system were characterized. The potential of BFE@BSA NPs as photothermal transduction agents and magnetic resonance imaging (MRI) contrast agents was explored. The synergistic anti-tumor effects consisting of BLM-induced chemotherapy, Fenton reactions-mediated chemodynamic therapy, and photothermal therapy-induced apoptosis were studied both in vitro and in vivo. Once internalized into tumor cells, released BLM could cause DNA damage, while Fenton reactions were initiated to produce highly toxic •OH. Upon laser irradiation, BFE@BSA NPs could convert light into heat to achieve synergistic effects. After intravenous administration, BFE@BSA NPs exhibited great therapeutic effects in 4T1 tumor xenograft model. Moreover, as T1-weighted MRI contrast agents, BFE@BSA NPs could provide diagnosis and treatment monitoring for individualized precise therapy.ConclusionsA nano-system that integrated imaging and combinational therapy (chemotherapy, chemodynamic therapy and photothermal therapy) were developed to kill the tumor and monitor therapeutic efficacy. This strategy provided an all-in-one theranostic nanoplatform for MRI-guided combinational therapy against TNBC.

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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