Carrier-Free Nanoassembly of Curcumin-Erlotinib Conjugate for Cancer Targeted Therapy.
Carrier-Free Nanoassembly of Curcumin-Erlotinib Conjugate for Cancer Targeted Therapy.
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DOI：
10.1002/adhm.202001128
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发表时间：
2020-10
影响因子：
10
通讯作者：
Xu P
中科院分区：
文献类型：
--
作者：
Cheng C;Sui B;Wang M;Hu X;Shi S;Xu P
抗癌药物负载的纳米颗粒已被广泛探索，以减少副作用，同时提高其治疗效果。然而，由于载药量低、药物过早释放、载体结构不标准、载体命运难以预测等原因，目前只有少数纳米药物获得FDA批准。据此，我们开发了一种基于姜黄素-埃罗替尼缀合物（EPC）的自组装的无载体纳米颗粒，其具有约105 nm的尺寸。与游离姜黄素和厄洛替尼的组合相比，EPC纳米组装体对BxPC-3胰腺癌细胞表现出更有效的细胞杀伤、更好的抗迁移和抗侵袭作用。此外，受益于被动和主动的肿瘤靶向效应，EPC纳米组装体可以有效地在异种移植胰腺肿瘤小鼠模型的肿瘤组织中积聚。因此，EPC有效地减少了胰腺肿瘤的生长，并将荷瘤小鼠的中位生存时间从22天延长到68天。此外，在接受EPC治疗的小鼠的主要器官中未检测到全身毒性。由于姜黄素-厄洛替尼缀合物的均匀性和易于放大，我们期望EPC可以转化为对抗胰腺癌和其他EGFR阳性癌症的有力工具。无载体纳米组装体EPC是由姜黄素-厄洛替尼偶联物制备而成，具有结构均匀、易于放大等优点。由于埃罗替尼外层的存在，EPC有效地在肿瘤中积聚并进入EGFR阳性癌细胞。由于姜黄素和厄洛替尼的协同作用，EPC可以减少肿瘤的生长，延长胰腺癌动物的生存时间。
Anticancer drug-loaded nanoparticles have been explored extensively to decrease side effects while improving their therapeutic efficacy. However, due to the low drug loading content, premature drug release, non-standardized carrier structure, and difficulty in predicting the fate of the carrier, only a few nanomedicines have been approved by the FDA. Hereby, we developed a carrier-free nanoparticle based on the self-assembly of the curcumin-erlotinib conjugate (EPC), which has a size of about 105 nm. The EPC nano-assembly exhibited more potent cell killing, better anti-migration and anti-invasion effects for BxPC-3 pancreatic cancer cells than the combination of free curcumin and erlotinib. Furthermore, benefited from both passive and active tumor targeting effect, EPC nano-assembly could effectively accumulate in the tumor tissue in a xenograft pancreatic tumor mouse model. Consequently, EPC effectively reduced the growth of pancreatic tumors and extended the median survival time of the tumor-bearing mice from 22 days to 68 days. In addition, no systemic toxicity was detected in the major organs from the mice receiving EPC treatment. Attributed to the uniformity of the curcumin-erlotinib conjugate and easiness of scaling up, we expect the EPC could be translated into a powerful tool in fighting against pancreatic cancer and other EGFR positive cancers. Carrier-free nano-assembly, EPC, is fabricated from a curcumin-erlotinib conjugate, which has the merit of uniform structure and easy scaling-up. Due to the existence of erlotinib outlayer, EPC effectively accumulates in the tumor and enters EGFR positive cancer cells. Benefit from the synergetic effect of curcumin and erlotinib, EPC reduces the growth of tumors and extends the survival time of the animal with pancreatic cancer.
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DOI：
10.1080/01635581.2020.1783327
发表时间：
2020-07-11
影响因子：
2.9
作者：
Eslami, Seyed Sadegh;Jafari, Davod;Tarighi, Parastoo
通讯作者：
Tarighi, Parastoo
影响因子：
4.8
作者：
Hong, Yuan;Che, Shaomin;Ma, Hailin
通讯作者：
Ma, Hailin
影响因子：
7.2
作者：
Javadi, Samira;Rostamizadeh, Kobra;Fathi, Mojtaba
通讯作者：
Fathi, Mojtaba
DOI：
10.1186/s13046-015-0168-z
发表时间：
2015-05-15
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Li J;Xiang S;Zhang Q;Wu J;Tang Q;Zhou J;Yang L;Chen Z;Hann SS
通讯作者：
Hann SS
影响因子：
45.3
作者：
Moore, Malcolm J.;Goldstein, David;Parulekar, Wendy
通讯作者：
Parulekar, Wendy