Nanolipolee-007, a novel nanoparticle-based drug containing leelamine for the treatment of melanoma

Raghavendra Gowda, Subba Rao V Madhunapantula, Arati Sharma, Omer Kuzu, Gavin P. Robertson

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2328-2340
Number of pages13
JournalMolecular Cancer Therapeutics
Volume13
Issue number10
DOIs
Publication statusPublished - 31 Jul 2014
Externally publishedYes

Fingerprint

Nanoparticles
Melanoma
Pharmaceutical Preparations
Therapeutics
Neoplasms
Drug Delivery Systems
Dimethyl Sulfoxide
Phosphatidylinositol 3-Kinases
Biological Availability
Cholesterol
Cell Proliferation
Apoptosis
Growth
Proteins

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Medicine(all)

Cite this

Nanolipolee-007, a novel nanoparticle-based drug containing leelamine for the treatment of melanoma. / Gowda, Raghavendra; Madhunapantula, Subba Rao V; Sharma, Arati; Kuzu, Omer; Robertson, Gavin P.

In: Molecular Cancer Therapeutics, Vol. 13, No. 10, 31.07.2014, p. 2328-2340.

Research output: Contribution to journalArticle

Gowda, Raghavendra ; Madhunapantula, Subba Rao V ; Sharma, Arati ; Kuzu, Omer ; Robertson, Gavin P. / Nanolipolee-007, a novel nanoparticle-based drug containing leelamine for the treatment of melanoma. In: Molecular Cancer Therapeutics. 2014 ; Vol. 13, No. 10. pp. 2328-2340.
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