Mol Can Therap:納米脂質體攜帶特效藥可靶向殺滅黑色素瘤細胞

2014年10月27日 訊 /生物谷BIOON/ --近日，來自賓州州立大學醫學院(Penn State College of Medicine)的研究人員通過研究開發了一種納米顆粒，其可以將治療黑色素瘤的藥物直接運輸到癌症患處，相關研究刊登於國際雜誌Molecular Cancer Therapeutics上。

將癌症藥物運輸至患處非常困難，科學家們一直致力於開發新技術來克服藥物的天然局限性，比如如何將藥物裝載至納米顆粒中；研究者Gavin Robertson表示，藥物可以被包裝裝載於脂質球中，這種脂質球明顯小於頭髮的寬度，這就可以使得脂質球溶解於血流中從而抑制副作用的產生。包含藥物的納米顆粒隨後會隨著血流運輸至腫瘤患處，在腫瘤患處不斷積累並且釋放藥物殺滅癌細胞。

此前研究中研究者發現來自松樹皮的一種名為leelamine的衍生物具有抗癌特性，但是由於其在胃腸道吸收較差因此不能口服，而且由於其對紅細胞具有損傷作用也不能通過靜脈進行注射。本文中，研究者Robertson和其同時開發了一種裝載leelamine的納米脂質體-Nanolipolee-007，其可以通過靜脈注射而不損傷紅細胞，隨後Nanolipolee-007會在腫瘤患處積累，由於其尺寸較小因此其可以在腫瘤部位釋放leelamine來殺滅癌細胞。

Leelamine是一種獨特的藥物，其可以抑制癌細胞周圍的膽固醇運動從而關閉癌細胞生存所需的關鍵信號，一些諸如PI3K、MAPK和STAT3的蛋白質通路往往處於高度激活狀態，幫助癌細胞複製擴散，但在leelamine的作用下其都會被關閉從而引發癌細胞死亡，正常細胞中這些蛋白通路水平並不會太高。

研究者表示，納米顆粒可以幫助leelamine進一步邁向臨床試驗中，而我們也揭示了Nanolipolee-007對培養皿中生長的細胞的效應，以及其對小鼠腫瘤生長的抑制作用，leelamine可以有效抑制小鼠腫瘤的發展而不引發任何副作用。

目前包含leelamine的Nanolipolee-007是一種新型的藥物，其可以通過抑制癌細胞的膽固醇運輸來靶向殺滅癌細胞，未來還需要進行更多的研究來證明其安全可靠性，研究人員希望Nanolipolee-007可以早日進入到臨床試驗中來真正為開發治療黑色素瘤的靶向療法帶來幫助。（生物谷Bioon.com）

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

Raghavendra Gowda1,2,3,4, SubbaRao V. Madhunapantula1, Arati Sharma1,2,3,4, Omer F. Kuzu1,2, and Gavin P. Robertson1,2,3,4,5,6,7,*

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.