Parallelism to Conquer: Binary Supramolecular Peptide Amphiphiles Launch Synergistic Stromal Reprogramming to Remove the Baffle in Pancreatic Cancer Therapy
Parallelism to Conquer: Binary Supramolecular Peptide Amphiphiles Launch Synergistic Stromal Reprogramming to Remove the Baffle in Pancreatic Cancer Therapy
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并行征服：二元超分子肽两亲物启动协同基质重编程以消除胰腺癌治疗中的障碍
DOI：
10.1002/adfm.202203767
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发表时间：
2022-07
影响因子：
19
通讯作者：
Chihua Fang
中科院分区：
文献类型：
--
作者：
Weiqi Zhang;Jie Zhan;Ruizhi Zhao;Yangping Xu;Yinghua Zeng;Qiuqun Xiao;Wenyu Ye;Yuanyuan Wu;Yanbin Cai;Chihua Fang
In pancreatic cancer, the activation of quiescent pancreatic stellate cells (PSCs) is a critical event that leads to a characteristic dense desmoplastic stroma. The fibrotic network resulting from the bidirectional cross talk between pancreatic cancer cells (PCCs) and PSCs creates a complex tumor microenvironment that considerably hinders drug delivery and penetration. To improve pancreatic cancer treatment, a promising parallelization strategy with cross‐action property is urgently required that can simultaneously act on PCCs and PSCs to normalize activated PSCs (aPSCs), that is reverse them back to quiescent phenotype. Herein, a novel parallelization delivery system (CoA‐A&B‐γPGA) with dual‐pathway PSC quiescence restoration functions is designed. Metformin downregulates the secretion of transforming growth factor‐beta in PCCs, and all‐trans‐retinoic acid re‐educates aPSCs. CoA‐A&B‐γPGA thus induces aPSC quiescence and homeostatic restoration of desmoplastic stroma in vitro and in vivo. Importantly, CoA‐A&B‐γPGA exhibits deep penetration, improved accumulation and long‐term retention, and enhanced combination chemotherapy effects in multicellular spheroid and xenograft models. Furthermore, this dual‐targeting and co‐delivery system shows high specificity and sensitivity for detecting pancreatic cancer in patient samples. The innovative but simple peptide amphiphile co‐assembly strategy provides a new paradigm to design desired nanomedicines for stroma‐enriched pancreatic cancer therapy.
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影响因子：
50.3
作者：
Özdemir BC;Pentcheva-Hoang T;Carstens JL;Zheng X;Wu CC;Simpson TR;Laklai H;Sugimoto H;Kahlert C;Novitskiy SV;De Jesus-Acosta A;Sharma P;Heidari P;Mahmood U;Chin L;Moses HL;Weaver VM;Maitra A;Allison JP;LeBleu VS;Kalluri R
通讯作者：
Kalluri R
影响因子：
--
作者：
Yuanzhi Zhong;Jie Zhan;Guanghui Xu;Yumiao Chen;Qin Qin-Qin;Xu Liao;Shaodan Ma;Zhimou Yang;
通讯作者：
Yuanzhi Zhong;Jie Zhan;Guanghui Xu;Yumiao Chen;Qin Qin-Qin;Xu Liao;Shaodan Ma;Zhimou Yang;
DOI：
--
发表时间：
2021
期刊：
--
影响因子：
--
作者：
Yang Chen;Jiha Kim;Sujuan Yang;Huamin Wang;Chang-Jiun Wu;H. Sugimoto;Valerie S. LeBleu;R. Kalluri-R.-Kal
通讯作者：
Yang Chen;Jiha Kim;Sujuan Yang;Huamin Wang;Chang-Jiun Wu;H. Sugimoto;Valerie S. LeBleu;R. Kalluri-R.-Kal
影响因子：
10
作者：
Erica B. Peters;Nick D. Tsihlis;Mark R. Karver;S. M. Chin;Bruno Musetti;Benjamin T. Ledford;E. Bahnson-E.-Bahns
通讯作者：
Erica B. Peters;Nick D. Tsihlis;Mark R. Karver;S. M. Chin;Bruno Musetti;Benjamin T. Ledford;E. Bahnson-E.-Bahns
影响因子：
78.5
作者：
Sahai, Erik;Astsaturov, Igor;Werb, Zena
通讯作者：
Werb, Zena