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Surface Functionalization of Metal-Organic Frameworks for Improved Moisture Resistance
Published on: September 5, 2018
A metal-organic framework (MOF) built on surface-modified Cu nanoparticles eliminates tumors via multiple cascading
Guanghui An1, Heming Zheng1, Lianshan Guo2
1State Key Laboratory of Featured Metal Materials and Life-cycle Safety for Composite Structures, MOE Key Laboratory of New Processing Technology for Nonferrous Metals and Materials, and School of Resources, Environment and Materials, Guangxi University, Nanning 530004, China.
Abstract:
Tumors produce a hypoxic environment that greatly influences cancer treatment, and conventional chemotherapeutic drugs cannot selectively accumulate in the tumor region because of the lack of a tumor targeting mechanism, causing increased systemic toxicities and side effects. Hence, designing and developing new nanoplatforms that combine multimodal therapeutic regimens is essential to improve tumor therapeutic efficacy. Herein, we report the synthesis of ultrafine Cu nanoparticles loaded with a drug combination of cisplatin (Pt) and 1-methyl-d-tryptophan (1-MT) and externally coated with 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin (TCPP) photosensitizer, polydopamine (PDA) and CaO2 of MIL-101(Fe) as a new nanoplatform (Cu@MIL-101@PMTPC). The nanoplatform synergistically combined chemodynamic therapy (CDT), photodynamic therapy (PDT), and immunochemotherapy. The Fe3+ in MIL-101(Fe) and the surface Cu nanoparticles exhibited strong ability to consume intracellular glutathione (GSH), thereby generating a Fenton-like response in the tumor microenvironment (TME) with substantial peroxidase (POD)-like and superoxide dismutase (SOD)-like activities. In this design, we used the indoleamine 2,3-dioxygenase (IDO) inhibitor 1-MT to overcome chemotherapy-induced immune escape phenomena including enhanced CD8+ and CD4+ T cell expression, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) production, and accelerated immunogenic cell death. The targeted release of cisplatin loaded into Cu@MIL-101@PMTPC also reduced toxic side effects of chemotherapy. TCPP generated a large amount of singlet oxygen (1O2) upon specific laser irradiation to effectively kill tumor cells. CaO2 on the outer layer generated oxygen (O2) and hydrogen peroxide (H2O2) to ameliorate hypoxia in the tumor microenvironment, enhance the PDT effect, and provide a continuous supply of H2O2 for the Fenton-like reaction. Thus, this nanocarrier platform exhibited a powerful chemodynamic, photodynamic, and immunochemotherapeutic cascade, providing a new strategy for cancer treatment.
Insights
This study developed a novel nanoplatform combining chemodynamic therapy, photodynamic therapy, and immunochemotherapy to enhance cancer treatment. The innovative design targets tumors, reduces side effects, and boosts the immune response against cancer.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Tumor hypoxia and lack of drug targeting limit conventional chemotherapy efficacy, leading to systemic toxicity.
- Developing advanced nanoplatforms is crucial for combining multiple therapeutic strategies to improve tumor treatment.
- Multimodal cancer therapy offers a promising approach to overcome treatment resistance and reduce side effects.
Purpose of the Study:
- To synthesize and characterize a novel nanoplatform (Cu@MIL-101@PMTPC) for synergistic cancer therapy.
- To investigate the combined efficacy of chemodynamic therapy (CDT), photodynamic therapy (PDT), and immunochemotherapy.
- To evaluate the nanoplatform's ability to overcome tumor hypoxia and enhance anti-tumor immune responses.
Main Methods:
- Synthesis of ultrafine Cu nanoparticles loaded with cisplatin and 1-methyl-d-tryptophan (1-MT), coated with TCPP, PDA, and CaO2 on MIL-101(Fe).
- Evaluation of the nanoplatform's Fenton-like reaction, reactive oxygen species generation, and oxygen production capabilities.
- Assessment of the nanoplatform's ability to induce immunogenic cell death and modulate the tumor immune microenvironment.
Main Results:
- The Cu@MIL-101@PMTPC nanoplatform demonstrated potent CDT and PDT effects, generating reactive oxygen species and singlet oxygen.
- The nanoplatform effectively consumed glutathione, ameliorated tumor hypoxia by producing oxygen, and enhanced chemotherapy's immunogenic effects.
- 1-MT incorporation successfully reversed chemotherapy-induced immune escape, boosting T cell responses and cytokine production.
Conclusions:
- The developed nanoplatform offers a powerful cascade of chemodynamic, photodynamic, and immunochemotherapeutic effects for enhanced cancer treatment.
- This multimodal strategy effectively targets tumors, reduces systemic toxicity, and stimulates anti-tumor immunity.
- The Cu@MIL-101@PMTPC nanocarrier represents a promising new therapeutic strategy for overcoming challenges in cancer treatment.
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