Systemic Tumor Suppression via Macrophage-Driven Automated Homing of Metal-Phenolic-Gated Nanosponges for Metastatic Melanoma.
Systemic Tumor Suppression via Macrophage-Driven Automated Homing of Metal-Phenolic-Gated Nanosponges for Metastatic Melanoma.
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通过巨噬细胞驱动的金属酚门控纳米海绵自动归巢对转移性黑色素瘤的系统性肿瘤抑制。
DOI：
10.1002/advs.202207488
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发表时间：
2023-06
期刊：
影响因子：
15.1
通讯作者：
Guo, Junling
中科院分区：
文献类型：
--
作者：
Liao, Xue;Gong, Guidong;Dai, Mengyuan;Xiang, Zhenyu;Pan, Jiezhou;He, Xianglian;Shang, Jiaojiao;Blocki, Anna Maria;Zhao, Zongmin;Shields IV, C. Wyatt;Guo, Junling
关键词：
基于细胞的疗法包括向患者施用活细胞以进行直接治疗活动，在临床上取得了显著的成功，其中巨噬细胞由于其固有的趋化移动性和高效归巢肿瘤的能力而具有靶向药物递送的巨大潜力。然而，由于在实体瘤中平衡高载药量与高积累的复杂性，通过细胞系统的这种靶向药物递送仍然是一个重大挑战。本文报道了通过用生物响应性纳米海绵对肿瘤归巢巨噬细胞（Mφ）进行表面工程化的肿瘤靶向细胞药物递送系统（MAGN）。纳米海绵的孔被铁-鞣酸复合物堵塞，铁-鞣酸复合物通过保持封装的药物直到到达酸性肿瘤微环境来充当守门人。进行分子动力学模拟和界面力研究，以提供对基于多酚的超分子看门人对纳米海绵通道的“开-关”门控效应的机理见解。Mφ载体的细胞趋化性使得能够在体内有效地肿瘤靶向递送药物并全身抑制肿瘤负荷和肺转移。研究结果表明，MAGN平台提供了一种多功能的策略，可以有效地装载治疗药物，以治疗各种治疗药物的高负载能力的晚期转移性癌症。肿瘤靶向细胞药物递送系统是通过表面工程化巨噬细胞与由基于多酚的超分子“看门人”门控的生物响应性纳米海绵开发的。纳米海绵能够实现高载药量的药物，与细胞表面的牢固附着，以及在酸性肿瘤微环境中的药物控制释放，这导致化疗药物的有效肿瘤靶向递送和体内肿瘤的全身抑制。
Cell‐based therapies comprising the administration of living cells to patients for direct therapeutic activities have experienced remarkable success in the clinic, of which macrophages hold great potential for targeted drug delivery due to their inherent chemotactic mobility and homing ability to tumors with high efficiency. However, such targeted delivery of drugs through cellular systems remains a significant challenge due to the complexity of balancing high drug‐loading with high accumulations in solid tumors. Herein, a tumor‐targeting cellular drug delivery system (MAGN) by surface engineering of tumor‐homing macrophages (Mφs) with biologically responsive nanosponges is reported. The pores of the nanosponges are blocked with iron‐tannic acid complexes that serve as gatekeepers by holding encapsulated drugs until reaching the acidic tumor microenvironment. Molecular dynamics simulations and interfacial force studies are performed to provide mechanistic insights into the “ON‐OFF” gating effect of the polyphenol‐based supramolecular gatekeepers on the nanosponge channels. The cellular chemotaxis of the Mφ carriers enabled efficient tumor‐targeted delivery of drugs and systemic suppression of tumor burden and lung metastases in vivo. The findings suggest that the MAGN platform offers a versatile strategy to efficiently load therapeutic drugs to treat advanced metastatic cancers with a high loading capacity of various therapeutic drugs. A tumor‐targeting cellular drug delivery system is developed by surface‐engineering macrophages with biologically responsive nanosponges gated by polyphenol‐based supramolecular “gatekeepers”. The nanosponges enables a high‐loading content of drugs, robust attachment to cellular surfaces, and drug‐controlled release in an acidic tumor microenvironment, which results in the efficient tumor‐targeting delivery of chemotherapeutic drugs and the systemic suppression of tumors in vivo.
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影响因子：
14
作者：
Klyachko NL;Polak R;Haney MJ;Zhao Y;Gomes Neto RJ;Hill MC;Kabanov AV;Cohen RE;Rubner MF;Batrakova EV
通讯作者：
Batrakova EV
纳米颗粒负载的极化巨噬细胞用于增强肿瘤靶向和细胞化疗
影响因子：
26.6
作者：
Hou T;Wang T;Mu W;Yang R;Liang S;Zhang Z;Fu S;Gao T;Liu Y;Zhang N
通讯作者：
Zhang N
影响因子：
16.6
作者：
Kalin JH;Wu M;Gomez AV;Song Y;Das J;Hayward D;Adejola N;Wu M;Panova I;Chung HJ;Kim E;Roberts HJ;Roberts JM;Prusevich P;Jeliazkov JR;Roy Burman SS;Fairall L;Milano C;Eroglu A;Proby CM;Dinkova-Kostova AT;Hancock WW;Gray JJ;Bradner JE;Valente S;Mai A;Anders NM;Rudek MA;Hu Y;Ryu B;Schwabe JWR;Mattevi A;Alani RM;Cole PA
通讯作者：
Cole PA
DOI：
10.1002/adma.201706245
发表时间：
2018-05
期刊：
Advanced materials (Deerfield Beach, Fla.)
影响因子：
--
作者：
Chu D;Dong X;Shi X;Zhang C;Wang Z
通讯作者：
Wang Z
影响因子：
11.2
作者：
Chen, Xia;Niu, Shiwei;Zhu, Li-Min
通讯作者：
Zhu, Li-Min