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Nanocomposite plasters for the treatment of superficial tumors by chemo-photothermal combination therapy.

ABSTRACT: Introduction:Novel nanomedical systems are being developed as multiple therapeutic modalities because the combinational therapies for cancer on a single platform can have larger chance to address tumor heterogeneity and drug resistance than any mono-therapeutic modality. Methods:In this study, photothermal therapy (PTT) and chemotherapy (CT) were combined to treat squamous cell carcinoma by using a novel type of noninvasive plaster composed of carboxylated-reduced graphene oxide (rGO-COOH), gold nanorods (Au NRs), and doxorubicin (DOX). Firstly, DOX was loaded onto rGO-COOH to form DOX_rGO-COOH. Then, the obtained DOX_rGO-COOH and Au NRs were co-assembled to obtain nanocomposite multilayer. rGO-COOH and Au NRs were combined together to obtain high light-to-heat conversion efficiency. Using them as photothermal agents for PTT and using DOX in rGO-COOH as an anticancer drug for CT, their synergistic combination therapy could be applicable practically. Results:As a result, DOX_rGO-COOH/Au NRs showed higher photothermal effects than that showed by rGO-COOH or Au NRs alone. It also showed higher therapeutic effects than DOX_rGO-COOH (for CT) or Au nr (for PTT) alone. Moreover, the system can repeatedly produce heat and simultaneously stimulate the release of the encapsulated anticancer drug into the tumor upon being irradiated by near-infrared laser. In vivo experiments demonstrated that the squamous cell carcinoma-bearing mice treated with DOX_rGO-COOH/Au NRs were healthy for more than 60 days without tumor recurrence. Conclusion:The as-developed DOX_rGO-COOH/Au NRs plaster could be an effective, convenient, and noninvasive treatment option for treating superficial tumors.

SUBMITTER: Qi W

PROVIDER: S-EPMC6188105 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Nanocomposite plasters for the treatment of superficial tumors by chemo-photothermal combination therapy.

Qi Wei W Yan Jing J Sun Haifeng H Wang Hua H

International journal of nanomedicine 20181009

<h4>Introduction</h4>Novel nanomedical systems are being developed as multiple therapeutic modalities because the combinational therapies for cancer on a single platform can have larger chance to address tumor heterogeneity and drug resistance than any mono-therapeutic modality.<h4>Methods</h4>In this study, photothermal therapy (PTT) and chemotherapy (CT) were combined to treat squamous cell carcinoma by using a novel type of noninvasive plaster composed of carboxylated-reduced graphene oxide ( ...[more]

PMID: 30349247

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Project description:Tumor combination therapy using nano formulations with multimodal synergistic therapeutic effects shows great potential for complete ablation of tumors. However, targeting tumor metastases with nano structures is a major obstacle for therapy. Therefore, developing a combination therapy system able to target both primary tumors and their metastases at distant sites with synergistic therapy is desirable for the complete eradication of tumors. To this end, a dual chemodrug-loaded theranostic system based on single walled carbon nanohorns (SWNHs) is developed for targeting both primary breast tumors and their lung metastases. Methods: SWNHs were first modified simultaneously with poly (maleic anhydride-alt-1-octadecene) (C18PMH) and methoxypolyethyleneglycol-b-poly-D, L-lactide (mPEG-PLA) via hydrophobic-hydrophobic interactions and ?-? stacking. Then cisplatin and doxorubicin (DOX) (2.9:1 molar ratio) were sequentially loaded onto the modified nanohorns in a noninterfering way. After careful examinations of the release profiles of the loaded drugs and the photothermal performance of the dual chemodrug-loaded SWNHs, termed SWNHs/C18PMH/mPEG-PLA-DOX-Pt, the dual drug chemotherapeutic and chemo-photothermal synergetic therapeutic effects on tumor cells were evaluated. Subsequently, the in vivo behavior and tumor accumulation of the drug-loaded SWNHs were studied by photoacoustic imaging (PAI). For chemo-photothermal therapy of tumors, 4T1 tumor bearing mice were intravenously injected with SWNHs/C18PMH/mPEG-PLA-DOX-Pt at a dose of 10 mg/kg b.w. (in SWNHs) and tumors were illuminated by an 808 nm laser (1W/cm2 for 5 min) 24 h post-injection. Results: DOX and cisplatin were loaded onto the modified SWNHs with high efficiency (44 wt% and 66 wt%, respectively) and released in a pH-sensitive, tandem and sustainable manner. The SWNHs/C18PMH/mPEG-PLA-DOX-Pt had a hydrodynamic diameter of 182 ± 3.2 nm, were highly stable in physiological environment, and had both dual drug chemotherapeutic (CI = 0.439) and chemo-photothermal synergistic antitumor effects (CI = 0.396) in vitro. Moreover, the dual drug-loaded SWNHs had a long blood half-life (10.9 h) and could address both the primary breast tumors and their lung metastases after intravenous administration. Consequently, chemo-photothermal combination therapy ablated the primary tumors and simultaneously eradicated the metastatic lung nodules. Conclusion: Our study demonstrates that SWNHs/C18PMH/mPEG-PLA-DOX-Pt is highly potent for chemo-photothermal combination therapy of primary tumors and cocktail chemotherapy of their metastases at a distant site.

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Nanocomposite plasters for the treatment of superficial tumors by chemo-photothermal combination therapy.

Publications

Nanocomposite plasters for the treatment of superficial tumors by chemo-photothermal combination therapy.

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