P-Glycoprotein-Targeted Photothermal Therapy of Drug-Resistant Cancer Cells Using Antibody-Conjugated Carbon Nanotubes.
P-Glycoprotein-Targeted Photothermal Therapy of Drug-Resistant Cancer Cells Using Antibody-Conjugated Carbon Nanotubes.
复制标题
DOI：
10.1021/acsami.8b11974
复制
发表时间：
2018-10-03
影响因子：
9.5
通讯作者：
Ming X
中科院分区：
文献类型：
--
作者：
Suo X;Eldridge BN;Zhang H;Mao C;Min Y;Sun Y;Singh R;Ming X
P-糖蛋白（Pgp）介导的多药耐药（MDR）是肿瘤治疗面临的一个严峻挑战。由于使用小分子抑制剂的常规方法由于缺乏癌症特异性而在临床开发中失败，我们开发了Pgp靶向碳纳米管，通过将基于抗体的癌症靶向和局部肿瘤消融与光热疗法相结合来实现高度癌症特异性治疗。通过与磷脂-聚（乙二醇）的致密涂层，我们已经设计了多壁碳纳米管（MWCNTs），其显示最小的非特异性细胞相互作用和最大的细胞间扩散。在用抗Pgp抗体化学修饰后，这些多壁碳纳米管显示出高度的Pgp特异性细胞摄取。靶向多壁碳纳米管的治疗在光照射后在MDR癌细胞中引起显著的细胞毒性，而它们在黑暗中没有引起任何毒性或对不表达Pgp的正常细胞的光毒性。由于良好的肿瘤内扩散和Pgp特异性细胞摄取，靶向多壁碳纳米管在MDR癌细胞的肿瘤球体中产生强烈的光毒性，这是一种用于研究肿瘤渗透和治疗的3-D肿瘤模型。总之，我们已经开发了一种高度Pgp特异性的多壁碳纳米管，可以为其他方法失败的MDR癌症提供有效的治疗。
P-glycoprotein (Pgp)-medicated multidrug resistance (MDR) remains a formidable challenge to cancer therapy. As conventional approaches using small-molecule inhibitors failed in clinical development because of the lack of cancer specificity, we develop Pgp-targeted carbon nanotubes to achieve highly cancer-specific therapy through combining antibody-based cancer targeting and locoregional tumor ablation with photothermal therapy. Through a dense coating with phospholipid-poly(ethylene glycol), we have engineered multiwalled carbon nanotubes (MWCNTs) which show minimum nonspecific cell interactions and maximum intercellular diffusion. After chemically modified with an anti-Pgp antibody, these MWCNTs showed highly Pgp-specific cellular uptake. Treatment of the targeted MWCNTs caused dramatic cytotoxicity in MDR cancer cells upon photoirradiation, whereas they did not cause any toxicity in the dark or phototoxicity toward normal cells that do not express Pgp. Because of excellent intratumor diffusion and Pgp-specific cellular uptake, the targeted MWCNTs produced strong phototoxicity in tumor spheroids of MDR cancer cells, a 3-D tumor model for studying tumor penetration and therapy. In conclusion, we have developed a highly Pgp-specific MWCNTs that may provide an effective therapy for MDR cancers where other approaches have failed.
登录
查看更多内容
影响因子：
2.4
作者：
Carpentier, Alexandre;Chauvet, Dorian;Delattre, Jean-Yves
通讯作者：
Delattre, Jean-Yves
影响因子：
14
作者：
Burke, Andrew R.;Singh, Ravi N.;Carroll, David L.;Wood, James C. S.;D'Agostino, Ralph B., Jr.;Ajayan, Pulickel M.;Torti, Frank M.;Torti, Suzy V.
通讯作者：
Torti, Suzy V.
影响因子：
3.5
作者：
Hleb, E. Y.;Lapotko, D. O.
通讯作者：
Lapotko, D. O.
影响因子：
10
作者：
Huaux, Francois;de Bousies, Virginie d'Ursel;Lison, Dominique
通讯作者：
Lison, Dominique
影响因子：
16.6
作者：
Bonacchi, Sara;Cantelli, Andrea;Montalti, Marco
通讯作者：
Montalti, Marco