International Journal of Nanomedicine (Oct 2021)
Heptamethine Cyanine Dye MHI-148-Mediated Drug Delivery System to Enhance the Anticancer Efficiency of Paclitaxel
Abstract
Athira Raveendran,1,* Suchithra Poilil Surendran,2,* Jinhui Ser,1 Khurshed Alam,1 Hoonsung Cho,1 Yong Yeon Jeong3 1Department of Materials Science & Engineering, Chonnam National University, Gwangju, 61186, Republic of Korea; 2Department of Biomedical Sciences, Chonnam National University Medical School, Hwasun, 58128, Republic of Korea; 3Department of Radiology, Chonnam National University Hwasun Hospital, Hwasun, 58128, Republic of Korea*These authors contributed equally to this workCorrespondence: Hoonsung ChoDepartment of Materials Science & Engineering, Chonnam National University, Gwangju, 61186, Republic of KoreaTel +82-62-530-1717Fax +82-62-530-1699Email [email protected] Yeon JeongDepartment of Radiology, Chonnam National University Hwasun Hospital, Hwasun, 58128, Republic of KoreaEmail [email protected]: Paclitaxel (PTX) is a conventional chemotherapeutic drug that effectively treats various cancers. The cellular uptake and therapeutic potential of PTX are limited by its slow penetration and low solubility in water. The development of cancer chemotherapy methods is currently facing considerable challenges with respect to the delivery of the drugs, particularly in targeting the tumor site without exerting detrimental effects on the healthy surrounding cells. One possibility for improving the therapeutic potential is through the development of tumor-targeted delivery methods.Methods: We successfully synthesized paclitaxel-MHI-148 conjugates (PTX-MHI) by coupling PTX with the tumor-targeting heptamethine cyanine dye MHI-148. Synthesis and purification were characterized using the absorbance spectrum and the results of time-of-flight mass spectrometry. Cellular uptake and cytotoxicity studies were conducted in vitro and in vivo.Results: PTX-MHI accumulates in tumor cells but not in normal cells, as observed by in vitro near-infrared fluorescent (NIRF) imaging along with in vivo NIRF imaging and organ biodistribution studies. We observed that MHI-148-conjugated PTX shows greater efficiency in cancer cells than PTX alone, even in the absence of light treatment. PTX-MHI could also be used for specific drug delivery to intracellular compartments, such as the mitochondria and lysosomes of cancer cells, to improve the outcomes of tumor-targeting therapy.Conclusion: The results indicated that PTX-MHI-mediated cancer therapy exerts an excellent inhibitory effect on colon carcinoma (HT-29) cell growth with low toxicity in normal fibroblasts (NIH3T3).Keywords: cancer therapy, colon cancer, bioconjugation, fluorescent dye, paclitaxel
