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Hypoxia-ameliorated photothermal manganese dioxide nanoplatform for reversing doxorubicin resistance
Zhenzhen Chen1, Zhihong Liu2, Qian Zhang3
1Department of General Surgery, 900TH Hospital of Joint Logistics Support Force, Fuzhou, China.
Abstract:
Drug resistance is a huge hurdle in tumor therapy. Tumor hypoxia contributes to chemotherapy resistance by inducing the hypoxia-inducible factor-1α (HIF-1α) pathway. To reduce tumor hypoxia, novel approaches have been devised, providing significant importance to reverse therapeutic resistance and improve the effectiveness of antitumor therapies. Herein, the nanosystem of bovine serum albumin (BSA)-templated manganese dioxide (MnO2) nanoparticles (BSA/MnO2 NPs) loaded with doxorubicin (DOX) (DOX-BSA/MnO2 NPs) developed in our previous report was further explored for their physicochemical properties and capacity to reverse DOX resistance because of their excellent photothermal and tumor microenvironment (TME) response effects. The DOX-BSA/MnO2 NPs showed good biocompatibility and hemocompatibility. Meanwhile, DOX-BSA/MnO2 NPs could greatly affect DOX pharmacokinetic properties, with prolonged circulation time and reduced cardiotoxicity, besides enhancing accumulation at tumor sites. DOX-BSA/MnO2 NPs can interact with H2O2 and H+ in TME to form oxygen and exhibit excellent photothermal effect to further alleviate hypoxia due to MnO2, reversing DOX resistance by down-regulating HIF-1α expression and significantly improving the antitumor efficiency in DOX-resistant human breast carcinoma cell line (MCF-7/ADR) tumor model. The hypoxia-ameliorated photothermal MnO2 platform is a promising strategy for revering DOX resistance.
Insights
Novel manganese dioxide nanoparticles loaded with doxorubicin (DOX-BSA/MnO2 NPs) alleviate tumor hypoxia and reverse drug resistance. This hypoxia-ameliorated photothermal platform shows promise for enhancing antitumor therapy effectiveness.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Drug resistance remains a significant challenge in cancer treatment.
- Tumor hypoxia promotes chemotherapy resistance via the hypoxia-inducible factor-1α (HIF-1α) pathway.
- Novel strategies are needed to overcome therapeutic resistance and improve antitumor efficacy.
Purpose of the Study:
- To investigate the physicochemical properties and drug resistance-reversing capacity of doxorubicin-loaded bovine serum albumin-templated manganese dioxide nanoparticles (DOX-BSA/MnO2 NPs).
- To evaluate the potential of this nanosystem to alleviate tumor hypoxia and enhance chemotherapy effectiveness.
Main Methods:
- Characterization of DOX-BSA/MnO2 NPs for physicochemical properties.
- Assessment of biocompatibility and hemocompatibility.
- Evaluation of DOX-BSA/MnO2 NPs' effects on doxorubicin pharmacokinetics and tumor accumulation.
- Investigation of the nanosystem's interaction with the tumor microenvironment (TME) components (H2O2, H+).
- Assessment of photothermal effect and hypoxia alleviation.
- Analysis of HIF-1α expression in a doxorubicin-resistant breast cancer model (MCF-7/ADR).
Main Results:
- DOX-BSA/MnO2 NPs demonstrated good biocompatibility and hemocompatibility.
- The nanoparticles improved doxorubicin pharmacokinetics, prolonging circulation time, reducing cardiotoxicity, and enhancing tumor accumulation.
- The nanosystem effectively interacted with TME components to produce oxygen and exert a photothermal effect, alleviating hypoxia.
- Hypoxia alleviation led to the downregulation of HIF-1α expression.
- Significant improvement in antitumor efficiency was observed in the DOX-resistant MCF-7/ADR tumor model.
Conclusions:
- The hypoxia-ameliorated photothermal MnO2 nanosystem is a promising strategy for reversing doxorubicin resistance.
- This approach offers a potential solution to overcome therapeutic resistance and enhance the efficacy of cancer treatments.
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