Perillo Emiliana, Porto Stefania, Falanga Annarita, Zappavigna Silvia, Stiuso Paola, Tirino Virginia, Desiderio Vincenzo, Papaccio Gianpaolo, Galdiero Massimiliano, Giordano Antonio, Galdiero Stefania, Caraglia Michele
Department of Pharmacy and DFM Scarl - University of Naples "Federico II", Naples, Italy.
Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
Oncotarget. 2016 Jan 26;7(4):4077-92. doi: 10.18632/oncotarget.6013.
New delivery systems including liposomes have been developed to circumvent drug resistance. To enhance the antitumor efficacy of liposomes encapsulating anti-cancer agents, we used liposomes externally conjugated to the 20 residue peptide gH625. Physicochemical characterization of the liposome system showed a size of 140 nm with uniform distribution and high doxorubicin encapsulation efficiency. We evaluated the effects of increasing concentrations of liposomes encapsulating Doxo (LipoDoxo), liposomes encapsulating Doxo conjugated to gH625 (LipoDoxo-gH625), empty liposomes (Lipo) or free Doxo on growth inhibition of either wild type (A549) or doxorubicin-resistant (A549 Dx) human lung adenocarcinoma. After 72 h, we found that the growth inhibition induced by LipoDoxo-gH625 was higher than that caused by LipoDoxo with an IC50 of 1 and 0.3 μM in A549 and A549 Dx cells, respectively. The data on cell growth inhibition were paralleled by an higher oxidative stress and an increased uptake of Doxo induced by LipoDoxo-gH625 compared to LipoDoxo, above all in A549 Dx cells. Cytometric analysis showed that the antiproliferative effects of each drug treatment were mainly due to the induction of apoptosis. In conclusion, liposomes armed with gH625 are able to overcome doxorubicin resistance in lung adenocarcinoma cell lines.
包括脂质体在内的新型递送系统已被开发出来以规避耐药性。为了增强包裹抗癌药物的脂质体的抗肿瘤功效，我们使用了与20个残基的肽gH625外部偶联的脂质体。脂质体系统的物理化学表征显示其大小为140 nm，分布均匀且阿霉素包封效率高。我们评估了递增浓度的包裹阿霉素的脂质体（LipoDoxo）、包裹与gH625偶联的阿霉素的脂质体（LipoDoxo-gH625）、空脂质体（Lipo）或游离阿霉素对野生型（A549）或阿霉素耐药（A549 Dx）人肺腺癌生长抑制的影响。72小时后，我们发现LipoDoxo-gH625诱导的生长抑制高于LipoDoxo，在A549和A549 Dx细胞中的IC50分别为1 μM和0.3 μM。与LipoDoxo相比，LipoDoxo-gH625诱导的更高氧化应激和阿霉素摄取增加与细胞生长抑制数据平行，尤其是在A549 Dx细胞中。细胞计数分析表明每种药物处理的抗增殖作用主要是由于诱导细胞凋亡。总之，配备gH625的脂质体能够克服肺腺癌细胞系中的阿霉素耐药性。
