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Updated: Jul 17, 2025
In vivo Bioluminescence Imaging of Tumor Hypoxia Dynamics of Breast Cancer Brain Metastasis in a Mouse Model
Published on: October 3, 2011
NIR diagnostic imaging of triple-negative breast cancer and its lymph node metastasis for high-efficiency
Yi Pan1,2,3, Longcai Liu1,3,4, Yichen He1,2,3
1Center for Rehabilitation Medicine, Rehabilitation and Sports Medicine Research Institute of Zhejiang Province, Department of Rehabilitation Medicine, Cancer Center, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, 310014, Zhejiang, China.
Background:
Triple-negative breast cancer (TNBC) possesses special biological behavior and clinicopathological characteristics, which is highly invasive and propensity to metastasize to lymph nodes, leading to a worse prognosis than other types of breast cancer. Thus, the development of an effective therapeutic method is significant to improve the survival rate of TNBC patients.
Results:
In this work, a liposome-based theranostic nanosystem (ILA@Lip) was successfully prepared by simultaneously encapsulating IR 780 as the photosensitizer and lenvatinib as an anti-angiogenic agent, together with banoxantrone (AQ4N) molecule as the hypoxia-activated prodrug. The ILA@Lip can be applied for the near-infrared (NIR) fluorescence diagnostic imaging of TNBC and its lymph node metastasis for multimodal therapy. Lenvatinib in ILA@Lip can inhibit angiogenesis by cutting oxygen supply, thereby leading to enhanced hypoxia levels. Meanwhile, large amounts of reactive oxygen species (ROS) were produced while IR 780 was irradiated by an 808 nm laser, which also rapidly exhausted oxygen in tumor cells to worsen tumor hypoxia. Through creating an extremely hypoxic in TNBC, the conversion of non-toxic AQ4N to toxic AQ4 was much more efficiency for hypoxia-activated chemotherapy. Cytotoxicity assay of ILA@Lip indicated excellent biocompatibility with normal cells and tissues, but showed high toxicity in hypoxic breast cancer cells. Also, the in vivo tumors treated by the ILA@Lip with laser irradiation were admirably suppressed in both subcutaneous tumor model and orthotopic tumor models.
Conclusion:
Utilizing ILA@Lip is a profound strategy to create an extremely hypoxic tumor microenvironment for higher therapeutic efficacy of hypoxia-activated chemotherapy, which realized collective suppression of tumor growth and has promising potential for clinical translation.
Insights
A novel liposome-based theranostic nanosystem (ILA@Lip) effectively treats triple-negative breast cancer (TNBC) by inducing severe hypoxia. This enhances hypoxia-activated chemotherapy and suppresses tumor growth, showing promise for clinical application.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Triple-negative breast cancer (TNBC) is aggressive and metastasizes readily, necessitating advanced therapeutic strategies.
- Current treatments for TNBC have limitations, highlighting the need for innovative approaches to improve patient survival rates.
Purpose of the Study:
- To develop a liposome-based theranostic nanosystem (ILA@Lip) for diagnosing and treating TNBC.
- To enhance the efficacy of hypoxia-activated chemotherapy in TNBC by creating a highly hypoxic tumor microenvironment.
Main Methods:
- Prepared ILA@Lip by encapsulating IR 780 (photosensitizer), lenvatinib (anti-angiogenic), and banoxantrone (AQ4N, hypoxia-activated prodrug).
- Utilized near-infrared (NIR) fluorescence imaging for TNBC and lymph node metastasis detection.
- Administered ILA@Lip with 808 nm laser irradiation to induce reactive oxygen species (ROS) and hypoxia, activating AQ4N chemotherapy.
Main Results:
- ILA@Lip demonstrated effective NIR fluorescence diagnostic imaging capabilities for TNBC.
- Lenvatinib and laser-induced ROS significantly enhanced tumor hypoxia, promoting AQ4N conversion to its toxic form (AQ4).
- In vivo studies showed significant suppression of tumor growth in both subcutaneous and orthotopic TNBC models with excellent biocompatibility.
Conclusions:
- ILA@Lip is a potent strategy for creating extreme tumor hypoxia, boosting chemotherapy efficacy.
- The developed nanosystem achieved collective tumor growth suppression and shows significant potential for clinical translation in TNBC treatment.
