In vivo biodistribution of siRNA and cisplatin administered using CD44-targeted hyaluronic acid nanoparticles.
In vivo biodistribution of siRNA and cisplatin administered using CD44-targeted hyaluronic acid nanoparticles.
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DOI：
10.1016/j.jconrel.2013.10.016
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发表时间：
2013-12-28
期刊：
影响因子：
--
通讯作者：
Amiji MM
中科院分区：
文献类型：
--
作者：
Ganesh S;Iyer AK;Gattacceca F;Morrissey DV;Amiji MM
多药耐药(MDR)是几种癌症临床治疗中的一个重要问题。克服多药耐药通常涉及多模式治疗方法，其中包括利用靶向纳米平台提高给药效率，以及可使癌细胞对药物治疗敏感的战略。我们最近证实，串联表达抗凋亡基因的siRNAs在顺铂耐药肿瘤中过高表达，然后使用CD44靶向透明质酸(HA)纳米粒(NPs)治疗挑战，在表达CD44的顺铂耐药肿瘤中诱导协同抗肿瘤反应。在目前的研究中，一种近红外(NIR)染料负载的透明质酸纳米粒被用来成像NPs静脉注射后的全身定位。注射到对顺铂敏感和耐药的人肺肿瘤活体小鼠体内。此外，我们还分别用超灵敏定量聚合酶链式反应和电感耦合等离子体质谱(ICPMS)定量测定了静脉注射后siRNA双链和顺铂在各组织器官中的剂量分布。荷瘤小鼠注射负载HA纳米粒。我们的发现表明，使用针对HA NPs的特定工程CD44的siRNA和顺铂的分布模式与肿瘤靶向能力以及联合治疗获得的活性和疗效有很好的相关性。
Multidrug resistance (MDR) is a significant problem in the clinical management of several cancers. Overcoming MDR generally involves multi-modal therapeutic approaches that integrates enhancement of delivery efficiency using targeted nano-platforms as well as strategies that can sensitize cancer cells to drug treatments. We recently demonstrated that tandem delivery of siRNAs that downregulate anti-apoptotic genes overexpressed in cisplatin resistant tumors followed by therapeutic challenge using cisplatin loaded in CD44 targeted hyaluronic acid (HA) nanoparticles (NPs) induced synergistic antitumor response in CD44 expressing tumors that are resistant to cisplatin. In the current study, a near infrared (NIR) dye-loaded HA NPs was employed to image the whole body localization of NPs after intravenous (i.v.) injection into live mice bearing human lung tumors that were sensitive and resistant to cisplatin. In addition, we quantified the siRNA duplexes and cisplatin dose distribution in various tissues and organs using an ultra-sensitive quantitative PCR method and inductively coupled plasma-mass spectrometry (ICP-MS), respectively, after i.v. injection of the payload loaded HA NPs in tumor bearing mice. Our findings demonstrate that the distribution pattern of the siRNA and cisplatin using specifically engineered CD44 targeting HA NPs correlated well with the tumor targeting capability as well as the activity and efficacy obtained with combination treatments.
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影响因子：
14
作者：
Ganesh, Shanthi;Iyer, Arun K.;Morrissey, David V.;Amiji, Mansoor M.
通讯作者：
Amiji, Mansoor M.
影响因子：
4.9
作者：
Jiang, Ge;Park, Kitae;Hahn, Sei Kwang
通讯作者：
Hahn, Sei Kwang
影响因子：
5.8
作者：
Saxena, V;Sadoqi, M;Shao, J
通讯作者：
Shao, J
DOI：
10.1016/j.jphotobiol.2004.01.002
发表时间：
2004-03-19
影响因子：
5.4
作者：
Saxena, V;Sadoqi, M;Shao, J
通讯作者：
Shao, J
影响因子：
2.9
作者：
Stratford, Suzanne;Stec, Summer;Beverly, Michael
通讯作者：
Beverly, Michael