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Novel redox-responsive polymeric magnetosomes with tunable magnetic resonance property for in vivo drug release visualization and dual-modal cancer therapy.

ABSTRACT: Monitoring of in vivo drug release from nan by non-invasive approaches Remains very challenging. Herein we report on novel redox-responsive polymeric magnetosomes (PolyMags) with tunable magnetic resonance imaging (MRI) properties for in vivo drug release monitoring and effective dual-modal cancer therapy. The encapsulation of doxorubicin (DOX) significantly decreased PolyMags' T2 contrast enhancement and transverse relaxation rate R2, depending on the drug loading level. The T2 enhancement and R2 could be recovered once the drug was released upon PolyMags' disassembly. T2 & T2* MRI and diffusion-weighted imaging (DWI) were utilized to quantitatively study the correlation between MRI signal changes and drug release, and discover the MR tuning mechanisms. We visualized the in vivo drug release pattern based on such tunable MRI capability via monitoring the changes in T2-weighted images, T2 & T2* maps and R2 & R2* values. Interestingly, the PolyMags possessed excellent photothermal effect, which could be further enhanced upon DOX loading. The PolyMags were highly efficacious to treat breast tumors on xenograft model with tumor-targeted photothermal-and chemo-therapy, achieving a complete cure rate of 66.7%. The concept reported here is generally applicable to other micellar and liposomal systems for image-guided drug delivery & release applications toward precision cancer therapy.

SUBMITTER: Wang Z

PROVIDER: S-EPMC6625784 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Novel redox-responsive polymeric magnetosomes with tunable magnetic resonance property for in vivo drug release visualization and dual-modal cancer therapy.

Wang Zhongling Z Xue Xiangdong X He Yixuan Y Lu Ziwei Z Jia Bei B Wu Hao H Yuan Ye Y Huang Yee Y Wang Han H Lu Hongwei H Lam Kit S KS Lin Tzu-Yin TY Li Yuanpei Y

Advanced functional materials 20180622 33

Monitoring of in vivo drug release from nan by non-invasive approaches Remains very challenging. Herein we report on novel redox-responsive polymeric magnetosomes (PolyMags) with tunable magnetic resonance imaging (MRI) properties for in vivo drug release monitoring and effective dual-modal cancer therapy. The encapsulation of doxorubicin (DOX) significantly decreased PolyMags' T2 contrast enhancement and transverse relaxation rate R2, depending on the drug lo ...[more]

PMID: 31303869

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Project description:BackgroundAlthough many treatments for breast cancer are available, poor tumour targeting limits the effectiveness of most approaches. Consequently, it is difficult to achieve satisfactory results with monotherapies. The lack of accurate diagnostic and monitoring methods also limit the benefits of cancer treatment. The aim of this study was to design a nanocarrier comprising porous gold nanoshells (PGNSs) co-decorated with methoxy polyethylene glycol (mPEG) and trastuzumab (Herceptin®, HER), a therapeutic monoclonal antibody that binds specifically to human epidermal receptor-2 (HER2)-overexpressing breast cancer cells. Furthermore, a derivative of the microtubule-targeting drug maytansine (DM1) was incorporated in the PGNSs.MethodsPrepared PGNSs were coated with mPEG, DM1 and HER via electrostatic interactions and Au-S bonds to yield DM1-mPEG/HER-PGNSs. SK-BR-3 (high HER2 expression) and MCF-7 (low HER2) breast cancer cells were treated with DM1-mPEG/HER-PGNSs, and cytotoxicity was evaluated in terms of cell viability and apoptosis. The selective uptake of the coated PGNSs by cancer cells and subsequent intracellular accumulation were studied in vitro and in vivo using inductively coupled plasma mass spectrometry and fluorescence imaging. The multimodal imaging feasibility and synergistic chemo-photothermal therapeutic efficacy of the DM1-mPEG/HER-PGNSs were investigated in breast cancer tumour-bearing mice. The molecular mechanisms associated with the anti-tumour therapeutic use of the nanoparticles were also elucidated.ResultThe prepared DM1-mPEG/HER-PGNSs had a size of 78.6 nm and displayed excellent colloidal stability, photothermal conversion ability and redox-sensitive drug release. These DM1-mPEG/HER-PGNSs were taken up selectively by cancer cells in vitro and accumulated at tumour sites in vivo. Moreover, the DM1-mPEG/HER-PGNSs enhanced the performance of multimodal computed tomography (CT), photoacoustic (PA) and photothermal (PT) imaging and enabled chemo-thermal combination therapy. The therapeutic mechanism involved the induction of tumour cell apoptosis via the activation of tubulin, caspase-3 and the heat shock protein 70 pathway. M2 macrophage suppression and anti-metastatic functions were also observed.ConclusionThe prepared DM1-mPEG/HER-PGNSs enabled nanodart-like tumour targeting, visibility by CT, PA and PT imaging in vivo and powerful tumour inhibition mediated by chemo-thermal combination therapy in vivo. In summary, these unique gold nanocarriers appear to have good potential as theranostic nanoagents that can serve both as a probe for enhanced multimodal imaging and as a novel targeted anti-tumour drug delivery system to achieve precision nanomedicine for cancers.

Dataset Information

Novel redox-responsive polymeric magnetosomes with tunable magnetic resonance property for in vivo drug release visualization and dual-modal cancer therapy.

Publications

Novel redox-responsive polymeric magnetosomes with tunable magnetic resonance property for <i>in vivo</i> drug release visualization and dual-modal cancer therapy.

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