Porphyrin-phospholipid liposomes permeabilized by near-infrared light.
Porphyrin-phospholipid liposomes permeabilized by near-infrared light.
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DOI：
10.1038/ncomms4546
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发表时间：
2014-04-03
影响因子：
16.6
通讯作者：
Lovell, Jonathan F.
中科院分区：
文献类型：
--
作者：
Carter, Kevin A.;Shao, Shuai;Hoopes, Matthew I.;Luo, Dandan;Ahsan, Bilal;Grigoryants, Vladimir M.;Song, Wentao;Huang, Haoyuan;Zhang, Guojian;Pandey, Ravindra K.;Geng, Jumin;Pfeifer, Blaine A.;Scholes, Charles P.;Ortega, Joaquin;Karttunen, Mikko;Lovell, Jonathan F.
将治疗性化合物递送至靶组织是治疗疾病的主要挑战。外部控制的药物释放系统具有选择性地增强局部递送的潜力。在这里，我们描述了脂质体掺杂卟啉磷脂，直接渗透近红外光。分子动力学模拟确定了一种新的光吸收单体酯化从临床批准的组件预测和实验证明，产生一个更稳定的卟啉双层。光诱导的膜透化能够与10摩尔%的卟啉-磷脂的脂质体包合物，并发生在本体或纳米级加热的情况下。脂质体在激光照射后重新密封，并且渗透性通过改变卟啉磷脂掺杂、照射强度或照射持续时间来调节。卟啉磷脂脂质体显示出肿瘤内注射后对包埋庆大霉素释放的空间控制和对包埋荧光团释放的时间控制。全身给药后，激光照射增强了小鼠异种移植物中活性负载的阿霉素的沉积，从而实现了有效的单次治疗抗肿瘤疗法。 使用外部触发剂递送治疗剂是用于改进靶向疾病治疗的有吸引力的途径。在这里，作者发现了一种用于光控膜透化的卟啉磷脂脂质体，并使用该系统在体内递送抗癌药物。
The delivery of therapeutic compounds to target tissues is a central challenge in treating disease. Externally controlled drug release systems hold potential to selectively enhance localized delivery. Here we describe liposomes doped with porphyrin–phospholipid that are permeabilized directly by near-infrared light. Molecular dynamics simulations identified a novel light-absorbing monomer esterified from clinically approved components predicted and experimentally demonstrated to give rise to a more stable porphyrin bilayer. Light-induced membrane permeabilization is enabled with liposomal inclusion of 10 molar % porphyrin–phospholipid and occurs in the absence of bulk or nanoscale heating. Liposomes reseal following laser exposure and permeability is modulated by varying porphyrin–phospholipid doping, irradiation intensity or irradiation duration. Porphyrin–phospholipid liposomes demonstrate spatial control of release of entrapped gentamicin and temporal control of release of entrapped fluorophores following intratumoral injection. Following systemic administration, laser irradiation enhances deposition of actively loaded doxorubicin in mouse xenografts, enabling an effective single-treatment antitumour therapy. The delivery of therapeutics using an external trigger is an attractive route for the improvement of targeted disease treatment. Here, the authors have discovered a porphyrin–phospholipid liposome for light-controlled membrane permeabilization and use the system to deliver an anticancer drug in vivo.
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影响因子：
5.5
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PEDERSEN, LG