Injectable liquid metal nanoflake hydrogel as a local therapeutic for enhanced postsurgical suppression of tumor recurrence
Injectable liquid metal nanoflake hydrogel as a local therapeutic for enhanced postsurgical suppression of tumor recurrence
复制标题
可注射液态金属纳米片水凝胶作为局部治疗剂，用于增强术后抑制肿瘤复发
DOI：
10.1016/j.cej.2021.129092
复制
发表时间：
2021-02-26
影响因子：
15.1
通讯作者：
Yang, Min
中科院分区：
文献类型：
--
作者：
Xiong, Jianjun;Yan, Junjie;Yang, Min
尽管纳米医学取得了很大的进展，但液态金属纳米液滴主要是作为光剂用于肿瘤光疗。然而，在合理设计和构建基于lm的化疗纳米平台时，还存在载药效率低、水稳定性差、表面化学对配体修饰的无菌性和敏感性以及形态控制困难等问题。本研究开发了一种局部可注射的lm -多柔比星（LM-DOX）纳米片包埋水凝胶，ph触发药物释放，以提高预防术后肿瘤复发的治疗效果。以超支化聚氨基胺（HPAA）为配体，制备的LM纳米液滴具有优异的水稳定性和独特的片状纳米形态，并且可以通过希夫碱反应方便地偶联化疗药物。与LM基纳米球或纳米棒（LMNSs或LMNRs）相比，LM纳米片（LMNFs）的DOX负载能力更高，达到63.5%。在Pluronic F-127 （LMNF-DOX@Gel）中进一步包封LMNFDOX，以减少突发药物释放，达到长期抗肿瘤效果，并将全身毒性降到最低。最后，将该纳米制剂注入肿瘤切除腔内进行局部化疗，切除残留肿瘤，治疗效果和生物安全性均优于游离药物。综上所述，基于lmnf的水凝胶给药系统是一种很有前景的癌症术后治疗候选药物。
Despite the great progress achieved in nanomedicine, liquid metal (LM) nanodroplets have been mostly implemented as photo-agents for tumor phototherapy. However, in the rational design and construction of LM-based nanoplatforms for chemotherapy, limitations such as low drug-loading efficiency (LE), poor water stability, sterile and sensitive surface chemistry against ligand modification, and difficult morphology control remain to be addressed. Here, a local injectable LM-doxorubicin (LM-DOX) nanoflake-imbedded hydrogel with pH-triggered drug release is developed to achieve an enhanced therapeutic efficacy for the prevention of postoperative tumor relapse. With hyperbranched poly(amido amine) (HPAA) as the ligand, the obtained LM nanodroplets presented excellent aqueous stability and a unique flaky nanomorphology, and chemotherapeutics can be facilely conjugated via Schiff-base reaction as well. Compared to LM-based nanospheres or nanorods (LMNSs or LMNRs), LM nanoflakes (LMNFs) exhibited much higher DOX loading capacity of 63.5%. Further encapsulation of LMNFDOX within Pluronic F-127 (LMNF-DOX@Gel) was used to diminish burst drug release, achieve long-term antitumor effect, and minimize systemic toxicity. Finally, this nano-formulation was injected into the tumor resection cavity for local chemotherapy to remove the residual tumor, achieving enhanced therapeutic efficacy and biosafety than free drugs. Overall, LMNF-based hydrogel drug delivery system represents a promising candidate for postsurgical cancer treatment.