We present a novel drug carrier consisting of plasmonic hollow gold nanoshells (HGN) chemically tethered to liposomes made temperature sensitive with lysolipids (LTSL). Continuous-wave irradiation by physiologically friendly near infra-red light at 800 nm for 2.5 minutes at laser intensities an order of magnitude below that known to damage skin generates heating localized to the liposome membrane. The heating increases the liposome permeability in an irradiation dose-dependent, but reversible manner, resulting in rapid release of small molecules such as the self-quenching dye carboxyfluorescein or the chemotherapeutic doxorubicin, without raising the bulk temperature. The local rise in nanoshell temperature under laser irradiation was inferred by comparing dye release rates from the LTSL via bulk heating to that induced by irradiation. Laser-irradiation of LTSL enables precise control of contents release with low temperature gradients confined to areas irradiated by the laser focus. The combined effects of rapid local release and localized hyperthermia provide a synergistic effect as shown by a near doubling of androgen resistant PPC-1 prostate cancer cell toxicity compared to the same concentration of free doxorubicin.

中文翻译：

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近红外光触发热敏脂质体快速、可逆释放


我们提出了一种新型药物载体，由化学束缚在溶血脂（LTSL）制成的温度敏感脂质体上的等离子体空心金纳米壳（HGN）组成。使用 800 nm 的生理友好型近红外光连续波照射 2.5 分钟，激光强度比已知会损伤皮肤的强度低一个数量级，会产生局部加热到脂质体膜。加热以辐射剂量依赖性但可逆的方式增加了脂质体的渗透性，导致小分子（例如自猝灭染料羧基荧光素或化疗阿霉素）的快速释放，而不提高本体温度。通过比较通过整体加热从 LTSL 中释放染料与通过辐射诱导的染料释放速率，推断出激光照射下纳米壳温度的局部升高。 LTSL 的激光照射能够精确控制内容物的释放，并且激光焦点照射的区域具有低温梯度。快速局部释放和局部热疗的联合作用提供了协同效应，与相同浓度的游离阿霉素相比，雄激素抗性 PPC-1 前列腺癌细胞毒性几乎加倍。