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Data Supplement from Nanolipolee-007, a Novel Nanoparticle-Based Drug Containing Leelamine for the Treatment of Melanoma

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posted on 2023-04-03, 14:24 authored by Raghavendra Gowda, SubbaRao V. Madhunapantula, Arati Sharma, Omer F. Kuzu, Gavin P. Robertson

Supplemental Figure S4. The in vitro release of tritium labeled leelamine from Nanolipolee-007 was measured at room temperature using a molecular weight cut off 25 kDa dialysis membrane. 68.32% of leelamine was released from Nanolipolee-007 within 36 hours.

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ARTICLE ABSTRACT

Malignant melanoma is a difficult cancer to treat due to the rapid development of resistance to drugs targeting single proteins. One response to this observation is to identify single pharmacologic agents that, due to a unique mechanism of action, simultaneously target multiple key pathways involved in melanoma development. Leelamine has been identified as functioning in this manner but has poor bioavailability in animals and causes lethality when administered intravenously. Therefore, a nanoliposomal-based delivery system has been developed, called Nanolipolee-007, which stably loads 60% of the compound. The nanoparticle was as effective at killing melanoma cells as leelamine dissolved in DMSO and was more effective at killing cultured melanoma compared with normal cells. Mechanistically, Nanolipolee-007 inhibited PI3K/Akt, STAT3, and MAPK signaling mediated through inhibition of cholesterol transport. Nanolipolee-007 inhibited the growth of preexisting xenografted melanoma tumors by an average of 64% by decreasing cellular proliferation, reducing tumor vascularization, and increasing cellular apoptosis, with negligible toxicity. Thus, a unique clinically viable nanoparticle-based drug has been developed containing leelamine for the treatment of melanoma that acts by inhibiting the activity of major signaling pathways regulating the development of this disease. Mol Cancer Ther; 13(10); 2328–40. ©2014 AACR.

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