Novel Nitric Oxide-Releasing Pluronic F-127 Organogel Inhibits Progression of Melanoma

Objectives: Melanoma is a malignant neoplasm of melanocyte cell origin located on the skin. While rare, it can also occur in the oral cavity, which progresses rapidly and proves to be aggressive. Excision is the only curative treatment whereby local recurrence and metastasis are significant risks. Thus, there are still clinical needs for novel interventions, where local treatment with nitric oxide (NO), an endogenous gasotransmitter, represents an attractive approach. NO can exert both tumorigenic and tumoricidal effects at low (nM) and high (µM) concentrations, respectively, which highlights the need for controlled delivery. Our group has developed a novel cyclodextrin NO-donor (CD-EOH₇/NO) and optimized a Pluronic F-127 organogel formulation for topical application. Pluronic F-127 organogel is a unique formulation as it is a liquid at cold temperatures and solidifies into a cream-like consistency when applied to the skin. The objective of this study was to examine the in vivo utility of CD-EOH₇/NO for controlling tumor growth and delineation of associated mechanisms.
Methods: Syngeneic B16-F10 melanoma tumor cells were injected subcutaneously into 8-week-old C57BL/6 female mice which were treated daily with topical or subcutaneous applications of CD-EOH₇/NO.
Results: Up to day 7, mice receiving topical application of CD-EOH₇/NO showed reduced tumor size compared to all controls, suggesting that NO slows the progression of melanoma growth. The largest difference was observed at day 7, where mice receiving topical CD-EOH₇/NO had an average tumor size of 10.3 mm² whereas the no treatment groups had an average tumor size of 20.1 mm². In addition, mice receiving subcutaneous administration of CD-EOH₇/NO presented with negligible or minimal (<3mm²) tumor growth up to 10-days post tumor cell injection.
Conclusions: These findings suggest that topical delivery of NO has promise as a novel therapeutic for treating malignant melanoma lesions, while subcutaneous administration of NO has potential for controlling progression of melanoma following excision.