Overcoming the Tumor Collagen Barriers: A Multistage Drug Delivery Strategy for DDR1-Mediated Resistant Colorectal Cancer Therapy

Cui, Guangman1,2; Deng, Shaohui3; Zhang, Biao1,2; Wang, Manchun4,5,6; Lin, Zhousheng7; Lan, Xinyue4,5,6; Li, Zelong7; Yao, Guangyu7; Yu, Meng4,5,6,8; Yan, Jun1,2,9

2024-07-01

10.1002/advs.202402107

ADVANCED SCIENCE   影响因子和分区

2198-3844

["The extracellular matrix (ECM) is critical for drug resistance in colorectal cancer (CRC). The abundant collagen within the ECM significantly influences tumor progression and matrix-mediated drug resistance (MMDR) by binding to discoidin domain receptor 1 (DDR1), but the specific mechanisms by which tumor cells modulate ECM via DDR1 and ultimately regulate TME remain poorly understand. Furthermore, overcoming drug resistance by modulating the tumor ECM remains a challenge in CRC treatment. In this study, a novel mechanism is elucidated by which DDR1 mediates the interactions between tumor cells and collagen, enhances collagen barriers, inhibits immune infiltration, promotes drug efflux, and leads to MMDR in CRC. To address this issue, a multistage drug delivery system carrying DDR1-siRNA and chemotherapeutic agents is employed to disrupt collagen barriers by silencing DDR1 in tumor, enhancing chemotherapy drugs diffusion and facilitating immune infiltration. These findings not only revealed a novel role for collagen-rich matrix mediated by DDR1 in tumor resistance, but also introduced a promising CRC treatment strategy.","A multistage nanomedicine (si/SN38-NP) actively targets to tumor ECM modulation, where si/SN38-NP are activated to liberate si-NP and SN38-NP. si-NP penetrates into tumor cells quickly due to its small size thereby silencing DDR1 and regulating collagen barriers. Tumor permeability is thus increased to enhance SN38-NP penetration and immune cells tumoral infiltration, finally achieving a synergistic chemo-immunotherapy effect in colorectal cancer. image"]

drug delivery ecm modulation multistage nanomedicine sirna nanocarriers

SCI ; EI

英语

通讯

National Natural Science Foundation of China["82273360","32301195","82172079"] ; Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer[2020B121201004] ; Guangdong Provincial Major Talents Project[2019JC05Y361] ; Natural Science Foundation of Guangdong Province[2023A1515030291] ; Guangdong Basic and Applied Basic Research Foundation[2021A1515110889] ; Science and Technology Planning Project of Guangzhou City[202206010085] ; Science and Technology Program of Guangzhou[202201011130280065] ; China Postdoctoral Science Foundation[2023M731565] ; Clinical Research Project of Nanfang Hospital["2020CR001","2020CR011"]

Chemistry ; Science & Technology - Other Topics ; Materials Science

Chemistry, Multidisciplinary ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary

WOS:001259691800001

WILEY

Web of Science

1.Southern Med Univ, Nanfang Hosp, Dept Gen Surg & Guangdong Prov Key Lab Precis Med, Guangzhou 510515, Peoples R China
2.Southern Med Univ, Nanfang Hosp, Guangdong Prov Key Lab Precis Med Gastrointestinal, Guangzhou 510515, Peoples R China
3.Southern Med Univ, Affiliated Hosp 10, Dongguan 523059, Guangdong, Peoples R China
4.Southern Med Univ, Sch Pharmaceut Sci, NMPA Key Lab Res & Evaluat Drug Metab, Guangzhou 510515, Peoples R China
5.Southern Med Univ, Sch Pharmaceut Sci, Guangdong Prov Key Lab New Drug Screening, Guangzhou 510515, Peoples R China
6.Southern Med Univ, Sch Pharmaceut Sci, Guangdong Hongkong Macao Joint Lab New Drug Screen, Guangzhou 510515, Peoples R China
7.Southern Med Univ, Nanfang Hosp, Breast Ctr, Dept Gen Surg, Guangzhou 510515, Peoples R China
8.Southern Med Univ, Zhujiang Hosp, Guangzhou 510282, Peoples R China
9.Jinan Univ, Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Dept Gastrointestinal Surg,Clin Med Coll 2,Affilia, Shenzhen 518020, Guangdong, Peoples R China

Cui, Guangman,Deng, Shaohui,Zhang, Biao,et al. Overcoming the Tumor Collagen Barriers: A Multistage Drug Delivery Strategy for DDR1-Mediated Resistant Colorectal Cancer Therapy[J]. ADVANCED SCIENCE,2024.

Cui, Guangman.,Deng, Shaohui.,Zhang, Biao.,Wang, Manchun.,Lin, Zhousheng.,...&Yan, Jun.(2024).Overcoming the Tumor Collagen Barriers: A Multistage Drug Delivery Strategy for DDR1-Mediated Resistant Colorectal Cancer Therapy.ADVANCED SCIENCE.

Cui, Guangman,et al."Overcoming the Tumor Collagen Barriers: A Multistage Drug Delivery Strategy for DDR1-Mediated Resistant Colorectal Cancer Therapy".ADVANCED SCIENCE (2024).