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2014 ; 13
(10
): 2328-40
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Nanolipolee-007, a novel nanoparticle-based drug containing leelamine for the
treatment of melanoma
#MMPMID25082958
Gowda R
; Madhunapantula SV
; Sharma A
; Kuzu OF
; Robertson GP
Mol Cancer Ther
2014[Oct]; 13
(10
): 2328-40
PMID25082958
show ga
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.
free
free
free
