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Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
Published on: December 1, 2016
Biomimetic oxygen delivery nanoparticles for enhancing photodynamic therapy in triple-negative breast cancer
Hanyi Fang1,2, Yongkang Gai1,2, Sheng Wang3
1Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Background:
Triple-negative breast cancer (TNBC) is a kind of aggressive breast cancer with a high rate of metastasis, poor overall survival time, and a low response to targeted therapies. To improve the therapeutic efficacy and overcome the drug resistance of TNBC treatments, here we developed the cancer cell membrane-coated oxygen delivery nanoprobe, CCm-HSA-ICG-PFTBA, which can improve the hypoxia at tumor sites and enhance the therapeutic efficacy of the photodynamic therapy (PDT), resulting in relieving the tumor growth in TNBC xenografts.
Results:
The size of the CCm-HSA-ICG-PFTBA was 131.3 ± 1.08 nm. The in vitro 1O2 and ROS concentrations of the CCm-HSA-ICG-PFTBA group were both significantly higher than those of the other groups (P < 0.001). In vivo fluorescence imaging revealed that the best time window was at 24 h post-injection of the CCm-HSA-ICG-PFTBA. Both in vivo 18F-FMISO PET imaging and ex vivo immunofluorescence staining results exhibited that the tumor hypoxia was significantly improved at 24 h post-injection of the CCm-HSA-ICG-PFTBA. For in vivo PDT treatment, the tumor volume and weight of the CCm-HSA-ICG-PFTBA with NIR group were both the smallest among all the groups and significantly decreased compared to the untreated group (P < 0.01). No obvious biotoxicity was observed by the injection of CCm-HSA-ICG-PFTBA till 14 days.
Conclusions:
By using the high oxygen solubility of perfluorocarbon (PFC) and the homologous targeting ability of cancer cell membranes, CCm-HSA-ICG-PFTBA can target tumor tissues, mitigate the hypoxia of the tumor microenvironment, and enhance the PDT efficacy in TNBC xenografts. Furthermore, the HSA, ICG, and PFC are all FDA-approved materials, which render the nanoparticles highly biocompatible and enhance the potential for clinical translation in the treatment of TNBC patients.
Insights
Triple-negative breast cancer (TNBC) is aggressive, but a new cancer cell membrane-coated nanoprobe (CCm-HSA-ICG-PFTBA) effectively targets tumors, reduces hypoxia, and enhances photodynamic therapy (PDT) efficacy, improving treatment outcomes.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Triple-negative breast cancer (TNBC) presents significant therapeutic challenges due to its aggressive nature, high metastatic potential, and resistance to conventional treatments.
- Hypoxia within the tumor microenvironment exacerbates TNBC's aggressiveness and limits the effectiveness of therapies like photodynamic therapy (PDT).
Purpose of the Study:
- To develop and evaluate a novel cancer cell membrane-coated oxygen delivery nanoprobe (CCm-HSA-ICG-PFTBA) for enhanced TNBC treatment.
- To investigate the potential of this nanoprobe to alleviate tumor hypoxia and improve PDT efficacy in TNBC models.
Main Methods:
- Fabrication of CCm-HSA-ICG-PFTBA nanoparticles (131.3 ± 1.08 nm) utilizing cancer cell membranes, human serum albumin (HSA), indocyanine green (ICG), and perfluorocarbon (PFTBA).
- In vitro assessment of reactive oxygen species (ROS) generation and in vivo evaluation using fluorescence imaging, 18F-FMISO PET imaging, and immunofluorescence staining to confirm hypoxia mitigation.
- In vivo efficacy studies involving photodynamic therapy (PDT) with near-infrared (NIR) laser irradiation on TNBC xenografts.
Main Results:
- CCm-HSA-ICG-PFTBA significantly increased in vitro 1O2 and ROS concentrations compared to control groups.
- In vivo imaging confirmed successful tumor targeting and significant reduction of tumor hypoxia 24 hours post-injection.
- PDT treatment with CCm-HSA-ICG-PFTBA and NIR resulted in the smallest tumor volume and weight, demonstrating significant therapeutic effects with no observed biotoxicity.
Conclusions:
- The CCm-HSA-ICG-PFTBA nanoprobe effectively targets tumors, combats hypoxia, and enhances PDT efficacy in TNBC models by leveraging cancer cell membrane properties and perfluorocarbon oxygen solubility.
- The use of FDA-approved materials (HSA, ICG, PFC) ensures high biocompatibility, suggesting strong potential for clinical translation in treating TNBC patients.

