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近日，國際著名雜志Science Translational Medicine在線刊登了國外研究人員最新研究成果“Preclinical Development and Clinical Translation of a PSMA-Targeted Docetaxel Nanoparticle with a Differentiated Pharmacological Profile”,，文章中研究者揭示了用納米粒攜帶抗癌藥物對于治療癌癥效果顯著,。
納米粒運輸治療法（Drug-smuggling nanoparticles）將會是最新的抵御癌癥的方法，早期的實驗結(jié)果顯示,，通過納米粒運輸癌癥藥物治療的方法可以明顯降低人類腫瘤的大小,。來自美國波士頓的研究者將癌癥藥物多西紫杉醇（docetaxel）填入納米粒中，然后注射入17個癌癥患者的血液中，這些患者對藥物有一定的耐藥性,，經(jīng)過42天后,，這些癌癥患者中，有兩個患者的腫瘤縮小了,，其余的患者腫瘤也不再生長了,。
當把這種含有癌癥藥物的納米粒注射入人的機體內(nèi)時，多西紫杉醇并不能夠識別出健康的細胞核癌細胞,，然而，納米粒卻可以起到識別的作用,，它可以通過于腫瘤細胞表面的分子反應(yīng)來識別腫瘤細胞,，從而釋放抗癌藥物，達到抑制腫瘤生長的目的,。而且針對每一個腫瘤細胞僅僅需要不到80%的藥物,。
研究者Jeffrey Hrkach表示，醫(yī)生們可以自由控制用藥濃度,，而不需要擔心藥物的毒性負面效應(yīng),，不過我們還需要進行更多的臨床試驗要確定用藥量。（生物谷：T.Shen編譯）
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doi:10.1126/scitranslmed.3003651
PMC:
PMID:
Preclinical Development and Clinical Translation of a PSMA-Targeted Docetaxel Nanoparticle with a Differentiated Pharmacological Profile
Jeffrey Hrkach1, Daniel Von Hoff2, Mir Mukkaram Ali1, Elizaveta Andrianova1, Jason Auer1, Tarikh Campbell1, David De Witt1, Michael Figa1, Maria Figueiredo1, Allen Horhota1, Susan Low1, Kevin McDonnell1, Erick Peeke1, Beadle Retnarajan1, Abhimanyu Sabnis1, Edward Schnipper1, Jeffrey J. Song1, Young Ho Song1, Jason Summa1, Douglas Tompsett1, Greg Troiano1, Tina Van Geen Hoven1, Jim Wright1, Patricia LoRusso3, Philip W. Kantoff4, Neil H. Bander5, Christopher Sweeney4, Omid C. Farokhzad6,*, Robert Langer7,* and Stephen Zale1,*
We describe the development and clinical translation of a targeted polymeric nanoparticle (TNP) containing the chemotherapeutic docetaxel (DTXL) for the treatment of patients with solid tumors. DTXL-TNP is targeted to prostate-specific membrane antigen, a clinically validated tumor antigen expressed on prostate cancer cells and on the neovasculature of most nonprostate solid tumors. DTXL-TNP was developed from a combinatorial library of more than 100 TNP formulations varying with respect to particle size, targeting ligand density, surface hydrophilicity, drug loading, and drug release properties. Pharmacokinetic and tissue distribution studies in rats showed that the NPs had a blood circulation half-life of about 20 hours and minimal liver accumulation. In tumor-bearing mice, DTXL-TNP exhibited markedly enhanced tumor accumulation at 12 hours and prolonged tumor growth suppression compared to a solvent-based DTXL formulation (sb-DTXL). In tumor-bearing mice, rats, and nonhuman primates, DTXL-TNP displayed pharmacokinetic characteristics consistent with prolonged circulation of NPs in the vascular compartment and controlled release of DTXL, with total DTXL plasma concentrations remaining at least 100-fold higher than sb-DTXL for more than 24 hours. Finally, initial clinical data in patients with advanced solid tumors indicated that DTXL-TNP displays a pharmacological profile differentiated from sb-DTXL, including pharmacokinetics characteristics consistent with preclinical data and cases of tumor shrinkage at doses below the sb-DTXL dose typically used in the clinic.
