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Application of a cationic amylose derivative loaded with single-walled carbon nanotubes for gene delivery therapy and photothermal therapy of colorectal cancer.

ABSTRACT: Single-walled carbon nanotubes (SWNTs) are cylindrical graphitic helix molecules that exhibit superb mechanical and physical properties. Many polymers, such as polyethylene glycol and glycated chitosan, have been used to modify SWNTs to enhance the stability and biocompatibility of delivery systems; thus, a novel modification for SWNTs with amylose derivatives containing poly(L-lysine) dendrons (ADP@SWNT) is developed. Infrared spectra analysis, ¹ H NMR analysis, circular dichroism spectra analysis and thermogravimetric analysis are used to characterize and confirm complex formation. The aqueous dispersion stability, cytotoxicity, gene transfection efficiency and photothermal effect of the complex are studied in vitro and in vivo. Results suggest that the ADP@SWNT complex is successfully synthesized with good water dispersion stability and pDNA transfection capacity. ADP@SWNT/TNFα inhibits tumor growth and metastasis both in vivo and in vitro, and the anti-tumor effect is enhanced by NIR irradiation, suggesting its high potential for application in tumor therapy.

SUBMITTER: Chen Z

PROVIDER: S-EPMC9302136 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Application of a cationic amylose derivative loaded with single-walled carbon nanotubes for gene delivery therapy and photothermal therapy of colorectal cancer.

Chen Zechang Z Zhuang Junbo J Pang Jiadong J Liu Zehao Z Zhang Penghao P Deng Haijun H Zhang Liming L Zhuang Baoxiong B

Journal of biomedical materials research. Part A 20220107 5

Single-walled carbon nanotubes (SWNTs) are cylindrical graphitic helix molecules that exhibit superb mechanical and physical properties. Many polymers, such as polyethylene glycol and glycated chitosan, have been used to modify SWNTs to enhance the stability and biocompatibility of delivery systems; thus, a novel modification for SWNTs with amylose derivatives containing poly(L-lysine) dendrons (ADP@SWNT) is developed. Infrared spectra analysis, <sup>1</sup> H NMR analysis, circular dichroism sp ...[more]

PMID: 34994069

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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 π-π 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.

Dataset Information

Application of a cationic amylose derivative loaded with single-walled carbon nanotubes for gene delivery therapy and photothermal therapy of colorectal cancer.

Publications

Application of a cationic amylose derivative loaded with single-walled carbon nanotubes for gene delivery therapy and photothermal therapy of colorectal cancer.

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