Activatable UCL/CT/MR-Enhanced in vivo Imaging-Guided Radiotherapy and Photothermal Therapy

2022 ◽  
Author(s):  
Jianming Ni ◽  
Huiting Xu ◽  
Yanqi Zhong ◽  
Yongping Zhou ◽  
Shudong Hu
Keyword(s):  
Tumor Microenvironment ◽  
Therapeutic Effect ◽  
In Vivo Imaging ◽  
Photothermal Therapy ◽  
Copper Sulphide ◽  
Hypoxic Tumor

Although sophisticated radiotherapy (RT) technology has been widely applied in clinical oncotherapy, unsatisfactory therapeutic effect resulted by hypoxic tumor microenvironment and complications are still prevalent. Herein, copper sulphide nanoparticles (CuS...

scholarly journals Atovaquone-HSA nano-drugs enhance the efficacy of PD-1 blockade immunotherapy by alleviating hypoxic tumor microenvironment

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Simeng Wang ◽  
Xinrui Zhou ◽  
Zekun Zeng ◽  
Mengjun Sui ◽  
Lihong Chen ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Disulfide Bonds ◽  
Tumor Targeting ◽  
Tumor Hypoxia ◽  
Animal Experiments ◽  
Complex Iii ◽  
Mitochondrial Activity ◽  
Hypoxic Tumor

Abstract Background Hypoxia is inherent character of most solid malignancies, leading to the failure of chemotherapy, radiotherapy and immunotherapy. Atovaquone, an anti-malaria drug, can alleviate tumor hypoxia by inhibiting mitochondrial complex III activity. The present study exploits atovaquone/albumin nanoparticles to improve bioavailability and tumor targeting of atovaquone, enhancing the efficacy of anti-PD-1 therapy by normalizing tumor hypoxia. Methods We prepared atovaquone-loaded human serum albumin (HSA) nanoparticles stabilized by intramolecular disulfide bonds, termed HSA-ATO NPs. The average size and zeta potential of HSA-ATO NPs were measured by particle size analyzer. The morphology of HSA-ATO NPs was characterized by transmission electron microscope (TEM). The bioavailability and safety of HSA-ATO NPs were assessed by animal experiments. Flow cytometry and ELISA assays were used to evaluate tumor immune microenvironment. Results Our data first verified that atovaquone effectively alleviated tumor hypoxia by inhibiting mitochondrial activity both in vitro and in vivo, and successfully encapsulated atovaquone in vesicle with albumin, forming HSA-ATO NPs of approximately 164 nm in diameter. We then demonstrated that the HSA-ATO NPs possessed excellent bioavailability, tumor targeting and a highly favorable biosafety profile. When combined with anti-PD-1 antibody, we observed that HSA-ATO NPs strongly enhanced the response of mice bearing tumor xenografts to immunotherapy. Mechanistically, HSA-ATO NPs promoted intratumoral CD8+ T cell recruitment by alleviating tumor hypoxia microenvironment, thereby enhancing the efficacy of anti-PD-1 immunotherapy. Conclusions Our data provide strong evidences showing that HSA-ATO NPs can serve as safe and effective nano-drugs to enhance cancer immunotherapy by alleviating hypoxic tumor microenvironment. Graphic abstract

scholarly journals A tumor-microenvironment-responsive nanomaterial for cancer chemo-photothermal therapy

RSC Advances ◽  
2020 ◽  
Vol 10 (37) ◽  
pp. 22091-22101
Author(s):  
Kaiyu Wang ◽  
Zhiyuan Cai ◽  
Rong Fan ◽  
Qian Yang ◽  
Tao Zhu ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Tumor Microenvironment ◽  
Therapeutic Effect ◽  
Photothermal Therapy

Endogenous hydrogen peroxide was utilized to control the release of agents for better tumor therapeutic effect and safety.

scholarly journals Atovaquone-HSA Nano-drugs Enhance the Efficacy of PD-1 Blockade Immunotherapy by Improving Hypoxic Tumor Microenvironment

2021 ◽  
Author(s):  
Simeng Wang ◽  
Xinrui Zhou ◽  
Zekun Zeng ◽  
Mengjun Sui ◽  
Lihong Chen ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Disulfide Bonds ◽  
Tumor Targeting ◽  
Tumor Hypoxia ◽  
Animal Experiments ◽  
Mitochondrial Activity ◽  
Hypoxic Tumor ◽  
Average Size

Abstract Background: Hypoxia is inherent character of most solid malignancies, leading to the failure of chemotherapy, radiotherapy and immunotherapy. Atovaquone, an anti-malaria drug, can alleviate tumor hypoxia by inhibiting mitochondrial complex Ⅲ activity. The present study exploits atovaquone/albumin nanoparticles to improve bioavailability and tumor targeting of atovaquone, enhancing the efficacy of anti-PD-1 therapy by normalizing tumor hypoxia.Methods: We prepared atovaquone-loaded human serum albumin (HSA) nanoparticles stabilized by intramolecular disulfide bonds, termed HSA-ATO NPs. The average size and zeta potential of HSA-ATO NPs were measured by particle size analyzer. The morphology of HSA-ATO NPs was characterized by transmission electron microscope (TEM). The bioavailability and safety of HSA-ATO NPs were assessed by animal experiments. Immunofluorescence and ELISA assays were used to evaluate tumor immune microenvironment.Results: Our data first verified that atovaquone effectively alleviated tumor hypoxia by inhibiting mitochondrial activity both in vitro and in vivo, and successfully encapsulated atovaquone in vesicle with albumin, forming HSA-ATO NPs of approximately 164 nm in diameter. We then demonstrated that the HSA-ATO NPs possessed excellent bioavailability, tumor targeting and a highly favorable biosafety profile. When combined with anti-PD-1 antibody, we observed that HSA-ATO NPs strongly enhanced the response of mice bearing tumor xenografts to immunotherapy. Mechanistically, HSA-ATO NPs promoted intratumoral CD8+ T cell recruitment by improving tumor hypoxia microenvironment, thereby enhancing the efficacy of anti-PD-1 immunotherapy. Conclusion: Our data provide strong evidences showing that HSA-ATO NPs can serve as safe and effective nano-drugs to enhance cancer immunotherapy by improving hypoxic tumor microenvironment.

Gold nanorods as a theranostic platform for in vitro and in vivo imaging and photothermal therapy of inflammatory macrophages

Nanoscale ◽  
2015 ◽  
Vol 7 (33) ◽  
pp. 13991-14001 ◽  
Author(s):  
Jinbao Qin ◽  
Zhiyou Peng ◽  
Bo Li ◽  
Kaichuang Ye ◽  
Yuxin Zhang ◽  
...  
Keyword(s):  
Gold Nanorods ◽  
In Vivo Imaging ◽  
Photothermal Therapy ◽  
Au Nanorods ◽  
Associated Diseases ◽  
Inflammatory Macrophages

This study shows that Au nanorods are a promising theranostic platform for the diagnosis and photothermal therapy of inflammation associated diseases.

scholarly journals A tumor microenvironment–induced absorption red-shifted polymer nanoparticle for simultaneously activated photoacoustic imaging and photothermal therapy

2021 ◽  
Vol 7 (12) ◽  
pp. eabe3588
Author(s):  
Shulong Wang ◽  
Liangliang Zhang ◽  
Jingjin Zhao ◽  
Min He ◽  
Yong Huang ◽  
...  
Keyword(s):  
Absorption Spectrum ◽  
Tumor Microenvironment ◽  
Redox Reaction ◽  
Photothermal Therapy ◽  
Near Infrared ◽  
Tumor Imaging ◽  
Photoacoustic Imaging ◽  
Diagnosis And Treatment ◽  
Induced Absorption

Tumor microenvironment–responsive therapy has enormous application potential in the diagnosis and treatment of cancer. The glutathione (GSH) level has been shown to be significantly increased in tumor tissues. Thus, GSH can be used as an effective endogenous molecule for diagnosis and tumor microenvironment–activated therapy. In this study, we prepared a tumor microenvironment–induced, absorption spectrum red-shifted, iron-copper co-doped polyaniline nanoparticle (Fe-Cu@PANI). The Cu(II) in this nanoparticle can undergo a redox reaction with GSH in tumors. The redox reaction induces a red shift in the absorption spectrum of the Fe-Cu@PANI nanoparticles from the visible to the near-infrared region accompanying with the etching of this nanoparticle, which simultaneously activates tumor photoacoustic imaging and photothermal therapy, thereby improving the accuracy of in vivo tumor imaging and the efficiency of photothermal therapy. The nanoparticle prepared in this study has broad application prospects in the diagnosis and treatment of cancer.

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