1] Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, USA [2] Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, USA.
Department of Chemistry and Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1.
Nat Commun. 2014 Apr 3;5:3546. doi: 10.1038/ncomms4546.
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.
将治疗化合物递送到靶组织是治疗疾病的一个核心挑战。外部控制的药物释放系统具有选择性增强局部递送的潜力。在这里，我们描述了掺杂卟啉磷脂的脂质体，它们可以直接被近红外光渗透。分子动力学模拟确定了一种新型的光吸收单体，它是由临床批准的成分酯化而来的，预测并实验证明它会导致卟啉双层更稳定。脂质体中包含 10 摩尔%的卟啉磷脂，就可以实现光诱导的膜通透性，并在没有体相或纳米级加热的情况下发生。激光照射后脂质体重新密封，并且通透性可以通过改变卟啉磷脂的掺杂、辐照强度或辐照持续时间来调节。在肿瘤内注射后，卟啉磷脂脂质体能够实现对包封的庆大霉素的空间控制释放和对包封的荧光染料的时间控制释放。系统给药后，激光照射增强了主动加载的阿霉素在小鼠异种移植中的沉积，从而实现了有效的单次治疗抗肿瘤治疗。
