Thermosensitive Liposome Formulated Indocyanine Green for Near-Infrared Triggered Photodynamic Therapy: In Vivo Evaluation for Triple-Negative Breast Cancer
The focus of this research was to formulate and evaluate a theranostic liposomal delivery system using indocyanine green (ICG) as a photosensitizer, triggered by near infrared (NIR) irradiation, for in vivo photodynamic therapy (PDT) of breast cancer.
Cytotoxicity of PDT using liposomal ICG (LPICG) as well as free ICG (FRICG) was evaluated in the human MDA-MB-468 triple-negative breast cancer (TNBC) cell line. NIR irradiation-induced increase in temperature was also monitored both in vitro and in vivo. Quantitative pharmacokinetic profile and fluorescence imaging-based biodistribution patterns of both formulations were obtained using the human TNBC xenograft model in nude mice. Overall safety, tolerability, and long-term anti-tumor efficacy of LPICG versus FRICG-mediated PDT was evaluated.
Significant loss of cell viability was achieved following photoactivation of LPICG via NIR irradiation. Temperatures of irradiated LPICG increased with increasing concentrations of loaded ICG, which correlated with significant rise of temperature compared to PBS in vivo (p < 0.01). Pharmacokinetic assessment revealed a significant increase in systemic distribution and circulation half-life of LPICG, and NIR fluorescence imaging demonstrated enhanced accumulation of liposomes within the tumor region. Tumor growth in mice treated with LPICG followed by NIR irradiation was significantly reduced compared to those treated with FRICG, saline, and irradiation alone.
In vivo photodynamic therapy using LPICG demonstrated targeted biodistribution and superior anti-tumor efficacy in a human TNBC xenograft model compared to FRICG. In addition, this unique delivery system exhibited a promising role in NIR image-guided delivery and real-time biodistribution monitoring of formulation with ICG serving as the fluorescent probe.
KEY WORDSindocyanine green liposomes near-infrared florescence imaging photodynamic therapy triple-negative breast cancer
Enhanced permeation and retention
Free indocyanine green
Liposomal indocyanine green
Reactive oxygen species
Triple-negative breast cancer
ACKNOWLEDGMENTS AND DISCLOSURES
We thank Dr. LaTonia Taliaferro-Smith and Tongrui Liu of the Winship Cancer Institute of Emory University for their donation of MDA-MB-468. We would also like to thank Dr. Ajay Banga of the Transdermal Delivery Laboratory at Mercer University for donation of pig ear skin tissues. We would like to acknowledge Dr. Ayyappa Chaturvedula and Vineet Goti from the Department of Pharmacy Practice at Mercer University for their valuable contributions to interpretation of pharmacokinetic analysis. This work was funded in part by the Georgia Cancer Coalition’s Cancer Research Award.
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