Doxorubicin encapsulated in stealth liposomes conferred with light-triggered drug release.
Doxorubicin encapsulated in stealth liposomes conferred with light-triggered drug release.
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DOI：
10.1016/j.biomaterials.2015.10.027
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发表时间：
2016-01
期刊：
影响因子：
14
通讯作者：
Lovell JF
中科院分区：
文献类型：
--
作者：
Luo D;Carter KA;Razi A;Geng J;Shao S;Giraldo D;Sunar U;Ortega J;Lovell JF
隐形脂质体可用于延长微囊化药物的血液循环时间。2摩尔%的卟啉磷脂(POP)可在近红外(NIR)光触发下从传统的立体稳定的隐形脂质体中释放阿霉素(Dox)。POP的类型和数量影响药物载药量、血清稳定性和近红外光诱导的药物释放。胆固醇和聚乙二醇化是Dox负载所必需的，但会减缓光触发的释放。DOX隐形脂质体在小鼠体内的循环半衰期较长，为21.9小时，储存数月后稳定性较好。静脉注射和近红外线照射后，经处理的人胰腺皮下移植瘤中Dox沉积增加了~7倍。光疗引起肿瘤轻度发热和复杂的肿瘤血流动力学改变。用载Dox的隐形POP脂质体(5-7 mg/kg Dox)进行单次化学光疗法可根除肿瘤，而相应的化疗或光动力疗法无效。用隐形POP脂质体进行低剂量3 mg/kg的Dox光疗效果优于最大耐受量(7 mg/kg)或常规长循环脂质体(21 mg/kg)。据我们所知，Dox隐形POP脂质体是第一个被报道的能够光触发药物释放的长循环纳米颗粒。
Stealth liposomes can be used to extend the blood circulation time of encapsulated therapeutics. Inclusion of 2 molar % porphyrin-phospholipid (PoP) imparted optimal near infrared (NIR) light-triggered release of doxorubicin (Dox) from conventional sterically stabilized stealth liposomes. The type and amount of PoP affected drug loading, serum stability and drug release induced by NIR light. Cholesterol and PEGylation were required for Dox loading, but slowed light-triggered release. Dox in stealth PoP liposomes had a long circulation half-life in mice of 21.9 hours and was stable in storage for months. Following intravenous injection and NIR irradiation, Dox deposition increased ~7 fold in treated subcutaneous human pancreatic xenografts. Phototreatment induced mild tumor heating and complex tumor hemodynamics. A single chemophototherapy treatment with Dox-loaded stealth PoP liposomes (at 5–7 mg/kg Dox) eradicated tumors while corresponding chemo- or photodynamic therapies were ineffective. A low dose 3 mg/kg Dox phototreatment with stealth PoP liposomes was more effective than a maximum tolerated dose of free (7 mg/kg) or conventional long-circulating liposomal Dox (21 mg/kg). To our knowledge, Dox-loaded stealth PoP liposomes represent the first reported long-circulating nanoparticle capable of light-triggered drug release.