Lipid-coated Cisplatin nanoparticles induce neighboring effect and exhibit enhanced anticancer efficacy.
Lipid-coated Cisplatin nanoparticles induce neighboring effect and exhibit enhanced anticancer efficacy.
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DOI：
10.1021/nn403606m
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发表时间：
2013-11-26
期刊：
影响因子：
17.1
通讯作者：
Huang, Leaf
中科院分区：
文献类型：
--
作者：
Guo, Shutao;Wang, Yuhua;Miao, Lei;Xu, Zhenghong;Lin, C. Michael;Zhang, Yuan;Huang, Leaf
由于顺铂（CDDP）的溶解性差，将其包封成具有高载药量和包封效率的纳米颗粒（NPs）一直是困难的。然而，这一障碍已经通过一种反向微乳方法克服了，利用CDDP的低溶解度，促进了具有高载药量（约80.8wt%）的纯顺铂纳米颗粒的合成。活性靶向CDDP NPs在人体内A375M黑色素瘤肿瘤细胞中有显著的积累。此外，每周静脉注射1 mg/kg剂量的CDDP NPs通过邻近效应获得了强大的抗肿瘤功效，且未引起肾毒性。邻近效应是在体内观察到摄取CDDP NPs的肿瘤细胞在凋亡后释放活性药物。通过扩散，先前未受影响的周围细胞显示摄入释放的药物并随后发生细胞凋亡。在体外实验中，用CDDP NPs孵育的A375M黑色素瘤细胞释放活性药物，诱导未处理的邻近细胞凋亡。然而，邻近效应是快速增殖的肿瘤细胞所特有的。体内肝脏组织的肝功能参数和H&E染色未发现CDDP NP处理组与对照组在组织健康方面有任何差异。与游离CDDP相比，CDDP NPs可以同时促进细胞毒性的增加和较小程度的副作用，因此CDDP NPs在低剂量的药物下显示出巨大的治疗潜力，同时增强了抗癌效果。
Encapsulation of cisplatin (CDDP) into nanoparticles (NPs) with high drug loading and encapsulation efficiency has been difficult due to the poor solubility of CDDP. However, this barrier has been overcome with a reverse microemulsion method appropriating CDDP’s poor solubility to our advantage promoting the synthesis of a pure cisplatin nanoparticle with a high drug loading capacity (approximately 80.8wt%). Actively targeted CDDP NPs exhibited significant accumulation in human A375M melanoma tumor cells in vivo. In addition, CDDP NPs achieved potent anti-tumor efficacy through the neighboring effect at a dose of 1 mg/kg when injected weekly via IV without inducing nephrotoxicity. The neighboring effect regards an observation made in vivo when the tumor cells that took up CDDP NPs released active drug following apoptosis. Via diffusion, surrounding cells that were previously unaffected showed intake of the released drug and their apoptosis soon followed. This observation was also made in vitro when A375M melanoma tumor cells incubated with CDDP NPs exhibited release of active drug and induced apoptosis on untreated neighboring cells. However, the neighboring effect was unique to rapidly proliferating tumor cells. Liver functional parameters and H&E staining of liver tissue in vivo failed to detect any difference between CDDP NP treated and control groups in terms of tissue health. By simultaneously promoting an increase in cytotoxicity and a lesser degree of side effects over free CDDP, CDDP NPs show great therapeutic potential with lower doses of drug while enhancing anti-cancer effectiveness.
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影响因子：
3
作者：
Newman, MS;Colbern, GT;Amantea, MA
通讯作者：
Amantea, MA
影响因子：
82.9
作者：
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通讯作者：
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影响因子：
10.8
作者：
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DOI：
10.1016/0584-8547(87)80122-2
发表时间：
1987-01-01
影响因子：
3.3
作者：
MCGAHAN, MC;TYCZKOWSKA, K
通讯作者：
TYCZKOWSKA, K
DOI：
10.1073/pnas.0915085107
发表时间：
2010-03-16
影响因子：
11.1
作者：
Kang, Tae-Hong;Lindsey-Boltz, Laura A.;Sancar, Aziz
通讯作者：
Sancar, Aziz