Targeted therapeutic nanotubes influence the viscoelasticity of cancer cells to overcome drug resistance.
Targeted therapeutic nanotubes influence the viscoelasticity of cancer cells to overcome drug resistance.
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DOI：
10.1021/nn501223q
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发表时间：
2014-05-27
期刊：
影响因子：
17.1
通讯作者：
Chen, Xiaoyuan
中科院分区：
文献类型：
--
作者：
Bhirde, Ashwinkumar A.;Chikkaveeraiah, Bhaskara V.;Srivatsan, Avinash;Niu, Gang;Jin, Albert J.;Kapoor, Ankur;Wang, Zhe;Patel, Sachin;Patel, Vyomesh;Gorbach, Alexander M.;Leapman, Richard D.;Gutkind, J. Silvio;Walker, Angela R. Hight;Chen, Xiaoyuan
关键词：
对化疗的耐药性是临床上超过90%的癌症患者治疗失败的主要原因。基于纳米技术的治疗替代品的研究有助于提供创新和有前途的策略，以克服多药耐药性（MDR）。通过靶向过表达CD 44的MDR癌细胞，我们在一个步骤中开发了一种自组装、自靶向、治疗性半导体单壁碳纳米管（sSWCNT）药物递送系统，该系统可以将化疗剂递送到药物敏感的OVCAR 8和耐药的OVCAR 8/ADR癌细胞。与游离DOX和磷脂PEG（PL-PEG）修饰的sSWCNT配方PEG-sSWCNT-DOX相比，具有围绕sSWCNT包裹的胆烷酸衍生的透明质酸（CAHA）生物聚合物并装载有多柔比星（DOX）的新型纳米配方CAHA-sSWCNT-DOX在杀死耐药性癌细胞方面更加有效。CAHA-sSWCNT-DOX比游离DOX和PL-PEG-sSWCNT-DOX更影响粘弹性，这又允许更多的药物分子被内化。静脉内注射CAHA-sSWCNT-DOX（12 mg/kg DOX当量），随后进行808 nm激光照射（1 W/cm 2，90 s），导致在皮下OVCAR 8/ADR耐药异种移植模型中完全肿瘤根除，而单独的游离DOX未能延迟肿瘤生长。我们新开发的CAHA-sSWCNT-DOX纳米制剂，其递送治疗剂并作为敏化剂影响药物摄取并以最小的抗性因子诱导细胞凋亡，提供了抵消多药耐药现象的新的有效手段。
Resistance to chemotherapy is the primary cause of treatment failure in over 90% of cancer patients in the clinic. Research in nanotechnology-based therapeutic alternatives has helped provide innovative and promising strategies to overcome multidrug resistance (MDR). By targeting CD44-overexpressing MDR cancer cells, we have developed in a single-step a self-assembled, self-targetable, therapeutic semiconducting single-walled carbon nanotube (sSWCNT) drug delivery system that can deliver chemotherapeutic agents to both drug-sensitive OVCAR8 and resistant OVCAR8/ADR cancer cells. The novel nanoformula with a cholanic acid-derivatized hyaluronic acid (CAHA) biopolymer wrapped around a sSWCNT and loaded with doxorubicin (DOX), CAHA-sSWCNT-DOX, is much more effective in killing drug-resistant cancer cells compared to the free DOX and phospholipid PEG (PL-PEG)-modified sSWCNT formula, PEG-sSWCNT-DOX. The CAHA-sSWCNT-DOX affects the viscoelastic property more than free DOX and PL-PEG-sSWCNT-DOX, which in turn allows more drug molecules to be internalized. Intravenous injection of CAHA-sSWCNT-DOX (12 mg/kg DOX equivalent) followed by 808 nm laser irradiation (1 W/cm2, 90 s) led to complete tumor eradication in a subcutaneous OVCAR8/ADR drug-resistant xenograft model, while free DOX alone failed to delay tumor growth. Our newly developed CAHA-sSWCNT-DOX nanoformula, which delivers therapeutics and acts as a sensitizer to influence drug uptake and induce apoptosis with minimal resistance factor, provides a novel effective means of counteracting the phenomenon of multidrug resistance.
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DOI：
10.2217/nnm.10.133
发表时间：
2011-04
期刊：
Nanomedicine (London, England)
影响因子：
--
作者：
Huang HC;Yang Y;Nanda A;Koria P;Rege K
通讯作者：
Rege K
影响因子：
17.1
作者：
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Rusling, James F.
DOI：
10.2217/nnm.10.90
发表时间：
2010-12
期刊：
Nanomedicine (London, England)
影响因子：
--
作者：
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通讯作者：
Rusling JF
影响因子：
15
作者：
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通讯作者：
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影响因子：
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作者：
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