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Detachable Dual-Targeting Nanoparticles for Improving the Antitumor Effect by Extracellular Matrix Depletion

Duan, Songchao, Sun, Fangfang, Qiao, Pan, Zhu, Zhihui, Geng, Meilin, Gong, Xiaobao, Li, Ying, Yao, Hanchun·2023·ACS Biomaterials Science & Engineering
DOI 10.1021/acsbiomaterials.2c01179
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Abstract

In the tumor microenvironment (TME), the extracellular matrix (ECM) produced by cancer-associated fibroblasts (CAFs) forms a dense barrier that prevents nanodrugs from penetrating into deep tumor sites, leading to unsatisfactory therapeutic effects. Recently, it has been found that ECM depletion and using small-sized nanoparticles are effective strategies. Herein, we reported a detachable dual-targeting nanoparticle (HA-DOX@GNPs-Met@HFn) based on reducing ECM for enhancing penetration. When these nanoparticles reached the tumor site, the nanoparticles were divided into two parts in response to matrix metalloproteinase-2 overexpressed in TME, causing a decrease in the nanoparticle size from about 124 to 36 nm. One part was Met@HFn, which was detached from the surface of gelatin nanoparticles (GNPs), which effectively targeted tumor cells and released metformin (Met) under acidic conditions. Then, Met downregulated the expression of the transforming growth factor β by the adenosine monophosphate-activated protein kinase pathway to inhibit the activity of CAFs, thereby suppressing the production of ECM including α-smooth muscle actin and collagen I. The other was the small-sized hyaluronic acid-modified doxorubicin prodrug with autonomous targeting ability, which was gradually released from GNPs and internalized into deeper tumor cells. Intracellular hyaluronidases triggered the release of doxorubicin (DOX), which killed tumor cells by inhibiting DNA synthesis. The combination o…

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Metadata

Authors
Duan, S., Sun, F., Qiao, P., Zhu, Z., Geng, M., Gong, X., Li, Y., & Yao, H.
Venue
ACS Biomaterials Science & Engineering
Publisher
American Chemical Society (ACS)
Published
2023-02-16
Volume
9
Issue
3
Pages
1437-1449
ISSN
2373-9878
DOI
10.1021/acsbiomaterials.2c01179
Cited by
23
References
4
Language
en
Licence
Funders
  • Science and Technology Department of Henan Province (222102310497)
  • National Natural Science Foundation of China (82272657)

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CoChat. (2026). Citation check: Detachable Dual-Targeting Nanoparticles for Improving the Antitumor Effect by Extracellular Matrix Depletion. https://app.cochat.ai/papers/10.1021/acsbiomaterials.2c01179
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Duan, S., Sun, F., Qiao, P., Zhu, Z., Geng, M., Gong, X., Li, Y., & Yao, H. (2023). Detachable Dual-Targeting Nanoparticles for Improving the Antitumor Effect by Extracellular Matrix Depletion. ACS Biomaterials Science & Engineering. https://doi.org/10.1021/acsbiomaterials.2c01179