Research Projects

Melanoma continues to represent a significant global health challenge, as evidenced by the increasing incidence rates and heightened mortality risk associated with this disease. Current chemotherapy agents such as 5-fluorouracil and imiquimod present considerable drawbacks, including skin irritation. Recent research has highlighted the potential of terpenoids, particularly gossypol (GsL), as promising anti-cancer agents. However, GsL faces several challenges, including poor solubility, rapid metabolism, inadequate absorption, and tautomerism, which collectively impact its bioavailability. The (-) enantiomer of GsL has demonstrated exceptional antitumor efficacy in phase II clinical trials when administered as a monotherapy for advanced malignancies. To address issues of insufficient drug release and limited penetration into tumor tissues, a strategy of selective targeting of ligands for overexpressed melanoma receptors, such as folic acid, will be employed. Recognizing the limitations of single-agent chemotherapy in treating melanoma, we are embarking on a strategic shift towards combination therapies that leverage advanced methodologies, including photothermal therapy (PTT). We aim to integrate PTT, utilizing Indocyanine green (ICG), with chemotherapy involving GsL to create a robust treatment strategy for melanoma. To enhance skin retention and optimize transdermal drug delivery, we will implement a thermo-responsive polymer, poloxamer, seamlessly transitioning from liquid to gel at body temperature. Moreover, to address the challenges of solubility and tautomerism associated with GsL, we have developed PTT-enabled surface-active ionic liquids (SAILs), which are approximately 80 nm in size and exhibit a low critical micelle concentration (data currently unpublished). These SAILs incorporate innovative derivatized cationic vinyl-imidazolium bromides and anionic ICG. Furthermore, to significantly improve GsL's solubility and bio-stability, we propose the application of self-assembling molecularly complexed ionic liquids (GsL@pSAILs) within a rigorously optimized folate-targeted pH-sensitive liposomal system (Gp@L). This system is designed for precise cancer cell delivery and effective endosomal escape. Creating poloxamer-based nanogels derived from GsL@pSAILs and Gp@L will ensure controlled and sustained release of both GsL and ICG as needed. By employing near-infrared radiation, we aim to enhance the generation of reactive oxygen species from ICG, further amplifying GsL's therapeutic effects synergistically. In addition, ICG will advance an innovative theranostic approach that enables multifaceted targeting of melanoma through real-time photoimaging, photothermal therapy, and chemotherapy with GsL. Our commitment lies in delivering a non-invasive, safe, and highly effective transdermal treatment solution that addresses the pressing needs in melanoma therapy.