Co-Delivery of Gemcitabine and Paclitaxel in cRGD-Modified Long Circulating Nanoparticles with Asymmetric Lipid Layers for Breast Cancer Treatment.
Co-Delivery of Gemcitabine and Paclitaxel in cRGD-Modified Long Circulating Nanoparticles with Asymmetric Lipid Layers for Breast Cancer Treatment.
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在 cRGD 修饰的具有不对称脂质层的长循环纳米颗粒中共同递送吉西他滨和紫杉醇用于乳腺癌治疗
DOI：
10.3390/molecules23112906
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发表时间：
2018-11-07
期刊：
影响因子：
--
通讯作者：
Jin Y
中科院分区：
文献类型：
--
作者：
Zhang J;Zhang P;Zou Q;Li X;Fu J;Luo Y;Liang X;Jin Y
联合化疗是癌症治疗中常见的临床实践。在此，将环状R ⑶（N-乙酰甘氨酰天冬氨酸）肽引入到脂质/钙/磷酸盐（LCP）不对称脂质层纳米颗粒的表面，用于紫杉醇（PTX）和吉西他滨单磷酸盐（GMP）（P/G-NP）的共递送。P/G-NPs的球形形态显示出均匀的粒径、高的包封率和PTX和GMP的载药量，具有正的zeta电位。P/G-NP稳定长达15天。这些环状RGD修饰的纳米颗粒的细胞摄取在2小时孵育期间显著高于未修饰的纳米颗粒。与游离PTX和GMP的组合（P/G-Free）相比，P/G-NPs表现出更长的循环寿命和对PTX和GMP的改善的吸收。聚乙二醇导致血浆浓度升高和表观分布容积（Vz）降低。与其他主要器官相比，24 h后纳米颗粒增强了肿瘤中的药物蓄积。P/G-NP几乎停止了肿瘤生长，几乎没有一般毒性的证据，而P/G-Free在16 mg/kg GMP和2.0 mg/kg PTX下仅具有适度的抑制作用。在P/G-NP组中检测到肿瘤内细胞凋亡水平增加约43.6%（TUNEL测定）。与GMP NP、PTX NP和P/G-Free相比，P/G-NP降低了B细胞淋巴瘤-2和B细胞淋巴瘤-超大蛋白的表达，并增加了裂解的聚ADP-核糖聚合酶-1的表达。肿瘤中钙网蛋白的表达也在PTX和GMP的共同递送后增加。P/G-NP的抗肿瘤作用比单独的P/G-Free、GMP NP或PTX NP更强，而没有明显的毒性。
Combination chemotherapy is a common clinical practice in cancer treatment. Here, cyclic RGD (arginylglycylaspartic acid) peptide was introduced to the surface of lipid/calcium/phosphate (LCP) asymmetric lipid layer nanoparticles for the co-delivery of paclitaxel (PTX) and gemcitabine monophosphate (GMP) (P/G-NPs). The sphere-like morphology of P/G-NPs displays a well-distributed particle size, and high entrapment efficiency and drug loading for both PTX and GMP, with a positive zeta potential. P/G-NPs were stable for up to 15 days. The cellular uptake of these cyclic RGD-modified nanoparticles was significantly higher than that of unmodified nanoparticles over 2 h incubation. Compared with the combination of free PTX and GMP (P/G-Free), P/G-NPs exhibited a longer circulation lifetime and improved absorption for PTX and GMP. Polyethylene glycol was responsible for a higher plasma concentration and a decreased apparent volume of distribution (Vz). Nanoparticles enhanced the drug accumulation in tumors compared with other major organs after 24 h. P/G-NPs nearly halted tumor growth, with little evidence of general toxicity, whereas P/G-Free had only a modest inhibitory effect at 16 mg/kg of GMP and 2.0 mg/kg of PTX. Increased levels of apoptosis within tumors were detected in P/G-NPs group by approximately 43.6% (TUNEL assay). When compared with GMP NPs, PTX NPs, and P/G-Free, P/G-NPs decreased expression of B-cell lymphoma-2 and B-cell lymphoma-extra large proteins, and increased expression of cleaved poly-ADP-ribose polymerase-1. Calreticulin expression in tumors also increased upon the co-delivery of PTX and GMP. The antitumor effect of P/G-NPs is more powerful than P/G-Free, GMP NP, or PTX NP alone, without obvious toxicity.
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DOI：
10.1186/1478-811x-8-31
发表时间：
2010-12-22
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Chaitanya GV;Steven AJ;Babu PP
通讯作者：
Babu PP
影响因子：
45.3
作者：
Albain, Kathy S.;Nag, Shona M.;O'Shaughnessy, Joyce
通讯作者：
O'Shaughnessy, Joyce
影响因子：
56.9
作者：
BROOKS, PC;CLARK, RAF;CHERESH, DA
通讯作者：
CHERESH, DA
使用脂质包被的介孔二氧化硅纳米颗粒平台协同吉西他滨和紫杉醇递送至小鼠的人类胰腺癌。
影响因子：
17.1
作者：
Meng, Huan;Wang, Meiying;Liu, Huiyu;Liu, Xiangsheng;Situ, Allen;Wu, Bobby;Ji, Zhaoxia;Chang, Chong Hyun;Nel, Andre E.
通讯作者：
Nel, Andre E.
影响因子：
3.8
作者：
Fiebig AA;Zhu W;Hollerbach C;Leber B;Andrews DW
通讯作者：
Andrews DW