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Janus Nanobullets Combine Photodynamic Therapy and Magnetic Hyperthermia to Potentiate Synergetic Anti-Metastatic Immunotherapy.

ABSTRACT: Photodynamic therapy (PDT) is clinically promising in destructing primary tumors but ineffective against distant metastases. This study reports the use of immunogenic nanoparticles mediated combination of PDT and magnetic hyperthermia to synergistically augment the anti-metastatic efficacy of immunotherapy. Janus nanobullets integrating chlorine e6 (Ce6) loaded, disulfide-bridged mesoporous organosilica bodies with magnetic heads (M-MONs@Ce6) are tailored for redox/pH-triggered photosensitizer release accompanying their matrix degradation. Cancer cell membrane cloaking enables favorable tumor-targeted accumulation and prolonged blood circulation time of M-MONs@Ce6. The combination of PDT and magnetic hyperthermia has a strong synergy anticancer activity and simultaneously elicits a sequence of immunogenic cell death, resulting in synergistically tumor-specific immune responses. When combined with anti-CTLA-4 antibody, the biomimetic and biodegradable nanoparticle enables the notable eradication of primary and deeply metastatic tumors with low systematic toxicity, thus potentially advancing the development of combined hyperthermia, PDT, and checkpoint blockade immunotherapy to combat cancer metastasis.

SUBMITTER: Wang Z

PROVIDER: S-EPMC6864517 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Janus Nanobullets Combine Photodynamic Therapy and Magnetic Hyperthermia to Potentiate Synergetic Anti-Metastatic Immunotherapy.

Wang Zheng Z Zhang Fan F Shao Dan D Chang Zhimin Z Wang Lei L Hu Hanze H Zheng Xiao X Li Xuezhao X Chen Fangman F Tu Zhaoxu Z Li Mingqiang M Sun Wen W Chen Li L Dong Wen-Fei WF

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20190912 22

Photodynamic therapy (PDT) is clinically promising in destructing primary tumors but ineffective against distant metastases. This study reports the use of immunogenic nanoparticles mediated combination of PDT and magnetic hyperthermia to synergistically augment the anti-metastatic efficacy of immunotherapy. Janus nanobullets integrating chlorine e6 (Ce6) loaded, disulfide-bridged mesoporous organosilica bodies with magnetic heads (M-MONs@Ce6) are tailored for redox/pH-triggered photosensitizer r ...[more]

PMID: 31763151

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Project description:Innovative synthesis routes revolutionized nanomaterial combination and design possibilities resulting in a new generation of fine-tuned nanoparticles featuring exquisite shape and constitution control. However, there is still room for improvement when it comes to the development of multi-functional nanoparticle agents merging a plurality of therapeutic functions to tackle tumors simultaneously by synergic mechanisms. Herein, we report the design of an optimized nanohybrid for cancer tri-therapy featuring a maghemite (γ-Fe2O3) nanoflower-like multicore nanoparticle conceived for efficient magnetic hyperthermia (MHT) and a spiky copper sulfide shell (IONF@CuS) with a high near-infrared (NIR) absorption coefficient suitable for photothermal (PTT) and photodynamic therapy (PDT). Methods: Spiky-like IONF@CuS nanohybrids were obtained through a straightforward and scalable water-based template sacrificial synthesis, which allows the shell shape control by tuning polyvinylpyrrolidone (PVP) concentration. A comprehensive characterization of nanohybrid size, shape and structural properties was carried out by combining complementary TEM, SEM, HR-TEM, EELS, XRD and NTA. The all-in-one therapeutic multi-functionality was assessed on cancer cells and on tumor-bearing nude mice. Results: Tests carried out on IONF@CuS nanohybrid aqueous dispersion demonstrated their impressive efficiency to convert light (conversion coefficient = 42 ± 6 %) and magnetic stimulation (SAR ~ 350 W g-1) into heat as well as to induce concurrent reactive oxygen species (ROS) formation upon laser irradiation. Such capabilities were further confirmed in cellular environment by in vitro tests and at the organism level by in vivo tests in a murine tumor model. Notably, complete tumor regression was obtained for the PTT mode at low Cu concentration. Overall, these results allowed determining windows of applicability for each therapy individually or in combination. Conclusions: Altogether, the obtained data evidence the successful synthesis of a unique tri-therapeutic nanoparticle featuring highly relevant assets for clinical translation such as reduced nanoparticle administered dose, reduced laser power exposure, reduced magnetic field frequency, and the possibility of serial heating cycles and therapy monitoring by photoacoustic (PA) and magnetic resonance imaging (MRI). Furthermore, the integration of the dual heating capability (MHT + PTT) with the PDT insult offers a unique asset to tackle tumors by multiple cytotoxic strategies in order to improve the therapeutic outcome in a broader spectrum of clinical conditions.

Dataset Information

Janus Nanobullets Combine Photodynamic Therapy and Magnetic Hyperthermia to Potentiate Synergetic Anti-Metastatic Immunotherapy.

Publications

Janus Nanobullets Combine Photodynamic Therapy and Magnetic Hyperthermia to Potentiate Synergetic Anti-Metastatic Immunotherapy.

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