A novel class of photo-triggerable liposomes containing DPPC:DC(8,9)PC as vehicles for delivery of doxorubcin to cells.

A novel class of photo-triggerable liposomes containing DPPC:DC(8,9)PC as vehicles for delivery of doxorubcin to cells.
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DOI:
10.1016/j.bbamem.2010.07.030
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发表时间:
2011-01
期刊:
Biochimica et biophysica acta
影响因子:
--
通讯作者:
Puri A
Puri A
中科院分区:
其他
文献类型:
--
作者:
Yavlovich A;Singh A;Blumenthal R;Puri A

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纳米颗粒介导的药物递送的成功取决于在限定的空间和时间内开发最佳药物释放策略(触发释放)。最近,我们报道了一类新的光致降解脂质体制备的二棕榈酰磷脂酰胆碱(DPPC)和光聚合的二乙炔磷脂(DC 8,9 PC),有效地释放包埋钙黄绿素(水溶性荧光染料)在紫外线(254 nm)处理。为了开发这些制剂在体内的应用,我们已经研究了这些脂质体的可见光光触发,以及释放的抗癌药物对细胞毒性的影响。将含有各种比例的DPPC:DC 8、9 PC和4摩尔% DSPE-PEG 2000的超声处理的脂质体加载有钙黄绿素(Ex/Em,485/517 nm)或化疗药物阿霉素(DOX,Ex/Em 490/590 nm)。我们的初步实验表明,514 nm激光处理脂质体含有10或20摩尔%的DC 8,9 PC 1-3分钟导致钙黄绿素的显着释放。基于这些结果,我们用装载DOX的脂质体进行了研究。首先,测定脂质体的生物物理性质(包括脂质体大小和稳定性)和DOX包封率。随后,检测514 nm激光对DOX释放的影响以及释放的DOX的细胞毒性。由于使用86:10:04摩尔比的DPPC:DC 8,9 PC:DSPE-PEG 2000的脂质体显示出最高的DOX包封,因此进一步研究了这些制剂。我们报道了(i)在0-50%血清存在下,脂质体在37°C下保留约70%的包封的DOX。(ii)514 nm激光处理导致DOX以波长特异性方式从脂质体释放。(iii)与未处理的样品相比,激光处理含有装载DOX的脂质体和细胞(Raji和MCF-7)的共培养物导致至少2-3倍的细胞杀伤改善。总之,本文所述的光致变色脂质体可以为未来的药物递送应用提供平台。据我们所知,这是第一份报告,证明改善细胞杀伤后,光触发释放的封装的抗癌剂从光敏脂质体。
Success of nanoparticle-mediated drug delivery is subject to development of optimal drug release strategies within defined space and time (triggered release). Recently, we reported a novel class of photo-triggerable liposomes prepared from dipalmitoyl phosphatidylcholine (DPPC) and photopolymerizable diacetylene phospholipid (DC8,9PC), that efficiently released entrapped calcein (a water soluble fluorescent dye) upon UV (254 nm) treatment. To develop these formulations for in vivo applications, we have examined phototriggering of these liposomes by visible light, and the effect of released anticancer drugs on cellular toxicity. Sonicated liposomes containing various ratios of DPPC:DC8,9PC and 4 mol% DSPE-PEG2000 were loaded with calcein (Ex/Em, 485/517 nm) or a chemotherapy drug, Doxorubicin (DOX, Ex/Em 490/590 nm). Our initial experiments showed that 514 nm laser treatment of liposomes containing 10 or 20 mol% DC8,9PC for 1–3 minutes resulted in significant release of calcein. Based on these results, we performed studies with DOX-loaded liposomes. First, biophysical properties (including liposome size and stability) and DOX encapsulation efficiency of the liposomes were determined. Subsequently, the effect of 514 nm laser on DOX release, and cellular toxicity by released DOX were examined. Since liposomes using the 86:10:04 mole ratio of DPPC:DC8,9PC:DSPE-PEG2000, showed highest encapsulation of DOX, these formulations were investigated further. We report that (i) Liposomes retained about 70% of entrapped DOX at 37°C in the presence of 0–50% serum. (ii) 514 nm laser treatment resulted in DOX release from liposomes in a wavelength specific manner. (iii) Laser treatment of co-cultures containing DOX-loaded liposomes and cells (Raji and MCF-7) resulted in at least 2–3 fold improved cell-killing as compared to untreated samples. Taken together, the phototriggerable liposomes described here may provide a platform for future drug delivery applications. To our knowledge, this is the first report demonstrating improved cell killing following light-triggered release of an encapsulated anticancer agent from photosensitive liposomes.
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发表时间: 2003-03-18
影响因子: 11.1
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