文獻(xiàn)：Design of pH-sensitive methotrexate prodrug-targeted curcumin nanoparticles for efficient dual-drug delivery and combination cancer therapy

文獻(xiàn)鏈接：https://www.tandfonline.com/doi/full/10.2147/IJN.S152312#d1e205

作者：Jiajiang Xie,Zhongxiong Fan,Yang Li,Yinying Zhang,Fei Yu,Guanghao Su

摘要：

Aim

We designed acid-labile methotrexate (MTX) targeting prodrug self-assembling nanoparticles loaded with curcumin (CUR) drug for simultaneous delivery of multi-chemotherapeutic drugs and combination cancer therapy.

Methods

A dual-acting MTX, acting as both an anticancer drug and as a tumor-targeting ligand, was coupled to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[aldehyde(polyethylene glycol)-2000] via Schiff’s base reaction. The synthesized prodrug conjugate (DSPE-PEG-Imine-MTX) could be self-assembled into micellar nanoparticles (MTX-Imine-M) in aqueous solution, which encapsulated CUR into their core by hydrophobic interactions (MTX-Imine-M-CUR).

結(jié)果

制備的MTX-Imine-M-CUR納米顆粒由內(nèi)部疏水性DSPE/CUR核心和外部親水性雙羥基聚乙二醇（PEG）外殼組成，外殼具有自靶向MTX前藥冠。

1,2-二硬脂酰-sn-甘油-3-磷酸乙酰胺-N-[醛（聚乙二醇）-2000]和MTX之間的亞胺連接體作為動態(tài)共價(jià)鍵，足夠強(qiáng)，即使在酸性pH下快速裂解，在生理pH下也能保持完整。MTX-imine-M-CUR可以通過葉酸受體介導(dǎo)的內(nèi)吞作用選擇性有效地將MTX和CUR編碼到癌癥細(xì)胞中，隨后通過內(nèi)體/溶酶體的酸性快速釋放CUR和活性形式的MTX。

此外，MTX-Imine-M-CUR在體外和體內(nèi)的*癌活性明顯高于pH不敏感的負(fù)載CUR的DSPE-PEGAmide-MTX組裝納米顆粒（MTX-Amide-M-CUR）、負(fù)載CUR（M-CUR）的MTX非偶聯(lián)DSPE-PEG組裝膠束納米顆粒、兩種游離藥物的組合和單個(gè)游離藥物。

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