Synergistic effect of the anti-PD-1 antibody with blood stable and reduction sensitive curcumin micelles on colon cancer.
Synergistic effect of the anti-PD-1 antibody with blood stable and reduction sensitive curcumin micelles on colon cancer.
复制标题
抗PD-1抗体与血液稳定且还原敏感的姜黄素胶束对结肠癌的协同作用。
DOI：
10.1080/10717544.2021.1921077
复制
发表时间：
2021-12
期刊：
影响因子：
6
通讯作者：
Cui ZK
中科院分区：
文献类型：
--
作者：
Gong F;Ma JC;Jia J;Li FZ;Wu JL;Wang S;Teng X;Cui ZK
姜黄素(1，7-bis(4-hydroxy-3-methoxyphenyl)-1，6-heptadiene-3，5-dione)是一种有效的抗癌药物，具有多种生物活性，但由于其疏水性、快速消除和在血液循环中的代谢，其临床转译受到严重限制。在此，我们的目标是揭示姜黄素在癌症治疗中作为免疫治疗协效剂的潜力。为了最大限度地减少过早释放，提高全身生物利用度，合理设计了一种血液稳定、还原敏感的姜黄素胶束制剂，该胶束制剂的释放可由癌细胞触发。我们合成了一种能够形成可逆的二硫键交联胶束(DCMS)的端树状大分子(mpeg-pla-(LA)4)。姜黄素负载的DCM(CuR/DCM)为球形，平均尺寸为24.6 nm。体外释放曲线表明，姜黄素在DCMS中的释放明显慢于非交联型胶束(NCMS)，而随着还原型谷胱甘肽(GSH)浓度的增加，姜黄素的释放速度加快。Cur/DCMS静脉给药稳定地将姜黄素保留在血液中，并有效地提高了系统的生物利用度。此外，在MC-38结肠癌异种移植模型中，Cur/DCMS与抗PD-1抗体联合使用时显示出协同抗癌效果。我们的结果加强了血液稳定的姜黄素纳米制剂与免疫治疗癌症治疗的整合。
Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is a potent anticancer drug with versatile biological activities, while the clinical translation of curcumin is severely limited due to its hydrophobicity, rapid elimination, and metabolism in the blood circulation. Herein, we aim to unravel the potential of curcumin as a synergistic agent with immunotherapy in the treatment of cancers. In an effort to minimize premature release and improve the systemic bioavailability, a superior blood stable and reduction sensitive curcumin micellar formulation, of which the release can be triggered by cancer cells, is rationally designed. We have synthesized a telodendrimer (mPEG-PLA-(LA)4) capable of forming reversible disulfide crosslinked micelles (DCMs). The curcumin loaded DCMs (Cur/DCMs) are spherical with a uniform size of 24.6 nm. The in vitro release profile demonstrates that curcumin releases significantly slower from DCMs than that from non-crosslinked micelles (NCMs), while the release can be accelerated with the increasing concentration of reducing agent glutathione (GSH). Intravenous administration of Cur/DCMs stably retains curcumin in the bloodstream and efficiently improves the systemic bioavailability. Furthermore, Cur/DCMs exhibit synergistic anticancer efficacy when combined with the anti-PD-1 antibody in an MC-38 colon cancer xenograft model. Our results potentiate the integration of blood stable curcumin nanoformulation and immunotherapy for cancer treatment.
登录
查看更多内容
DOI：
10.1016/j.biocel.2008.06.010
发表时间：
2009-01
影响因子：
4
作者：
Aggarwal, Bharat B.;Harikumar, Kuzhuvelil B.
通讯作者：
Harikumar, Kuzhuvelil B.
PD-1和PD-L1检查点信号传导抑制癌症免疫疗法：机制，组合和临床结果。
影响因子：
5.6
作者：
Alsaab HO;Sau S;Alzhrani R;Tatiparti K;Bhise K;Kashaw SK;Iyer AK
通讯作者：
Iyer AK
影响因子：
10.8
作者：
Dobrovoiskaia, Marina A.;Clogston, Jeffrey D.;Neun, Barry W.;Hall, Jennifer B.;Patri, Anil K.;McNeil, Scott E.
通讯作者：
McNeil, Scott E.
影响因子：
4.9
作者：
Ganta, Srinivas;Amiji, Mansoor
通讯作者：
Amiji, Mansoor
姜黄素通过COX-2和MAPK抑制作用抑制人肠微血管内皮细胞中VEGF介导的血管生成。
影响因子：
24.5
作者：
Binion, D. G.;Otterson, M. F.;Rafiee, P.
通讯作者：
Rafiee, P.