近日,，圣母大學(xué)的研究人員已經(jīng)研制出一種納米粒子，該粒子顯示出巨大的用于治療多發(fā)性骨髓瘤（MM）的潛力,。
治療MM的臨床醫(yī)生面對的困難之一就是：這種類型的癌細(xì)胞對先進(jìn)的化療治療手段產(chǎn)生了耐藥性,。
化學(xué)和生物分子工程助理教Başar Bilgiçer說：我們設(shè)計(jì)的納米粒子有多重功效。首先,，它們減少了多發(fā)性骨髓瘤對阿霉素抗藥性的產(chǎn)生,。第二，這些納米粒子實(shí)際上可以使得癌細(xì)胞盡可能對的接觸到藥物納米粒,。第三,，該納米粒還可以減少藥物對健康器官的毒性作用,。
該納米粒子涂有一種特殊的肽，是針對多發(fā)性骨髓瘤細(xì)胞外的特定受體,。多發(fā)性骨髓瘤細(xì)胞上的特定受體可以促使細(xì)胞粘附在骨髓組織上,，誘導(dǎo)細(xì)胞產(chǎn)生藥物的耐藥。通過使用新開發(fā)的肽,，納米粒子能夠綁定到該受體,，防止癌細(xì)胞粘附在骨髓。
粒子還能攜帶化療藥物,。當(dāng)一個粒子附著到MM細(xì)胞上,，細(xì)胞迅速接觸到納米粒子，然后粒子釋放藥物,，從而導(dǎo)致癌細(xì)胞死亡,。
同時有關(guān)老鼠動物實(shí)驗(yàn)研究表明，阿霉素納米粒子配方對其他組織如腎臟和肝臟的毒性大大減少,。
這項(xiàng)研究刊登在Blood Cancer Journal雜志上,。該研究由印第安納臨床與轉(zhuǎn)化科學(xué)研究所資金支持。（生物谷：Bioon.conm)
doi:10.1038/bcj.2012.10
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Rationally engineered nanoparticles target multiple myeloma cells, overcome cell-adhesion-mediated drug resistance, and show enhanced efficacy in vivo.
T Kiziltepe, J D Ashley, J F Stefanick, Y M Qi, N J Alves, M W Handlogten, M A Suckow, R M Navari, B Bilgicer.
In the continuing search for effective cancer treatments, we report the rational engineering of a multifunctional nanoparticle that combines traditional chemotherapy with cell targeting and anti-adhesion functionalities. Very late antigen-4 (VLA-4) mediated adhesion of multiple myeloma (MM) cells to bone marrow stroma confers MM cells with cell-adhesion-mediated drug resistance (CAM-DR). In our design, we used micellar nanoparticles as dynamic self-assembling scaffolds to present VLA-4-antagonist peptides and doxorubicin (Dox) conjugates, simultaneously, to selectively target MM cells and to overcome CAM-DR. Dox was conjugated to the nanoparticles through an acid-sensitive hydrazone bond. VLA-4-antagonist peptides were conjugated via a multifaceted synthetic procedure for generating precisely controlled number of targeting functionalities. The nanoparticles were efficiently internalized by MM cells and induced cytotoxicity. Mechanistic studies revealed that nanoparticles induced DNA double-strand breaks and apoptosis in MM cells. Importantly, multifunctional nanoparticles overcame CAM-DR, and were more efficacious than Dox when MM cells were cultured on fibronectin-coated plates. Finally, in a MM xenograft model, nanoparticles preferentially homed to MM tumors with ~10 fold more drug accumulation and demonstrated dramatic tumor growth inhibition with a reduced overall systemic toxicity. Altogether, we demonstrate the disease driven engineering of a nanoparticle-based drug delivery system, enabling the model of an integrative approach in the treatment of MM.
