Cited by 89Nanoparticle-Based Drug DeliveryNanoplatforms for cancer theranosticsAngiogenesis and VEGF in Cancer

Platelet-Mimicking Biotaxis Targeting Vasculature-Disrupted Tumors for Cascade Amplification of Hypoxia-Sensitive Therapy

Zhang, Mingkang, Ye, Jing-Jie, Xia, Yu, Wang, Zi-Yang, Li, Chu-Xin, Wang, Xiao-Shuang, Yu, Wuyang, Song, Wen +2 more·2019·ACS Nano

Abstract

Tumorous vasculature plays key roles in sustaining tumor growth. Vascular disruption is accompanied by internal coagulation along with platelet recruitment and the resulting suppression of oxygen supply. We intend to artificially create this physiological process to establish the mutual feedback between vascular disruption and platelet-mimicking biotaxis for the cascade amplification of hypoxia-dependent therapy. To prove this concept, mesoporous silica nanoparticles are co-loaded with a hypoxia-activated prodrug (HAP) and a vessel-disruptive agent and then coated with platelet membranes. Upon entering into tumors, our nanotherapeutic can disrupt local vasculature for tumor inhibition. This platelet membrane-coated nanoplatform shares the hemorrhage-tropic function with parental platelets and can be persistently recruited by the vasculature-disrupted tumors. In this way, the intratumoral vascular disruption and tumor targeting are biologically interdependent and mutually reinforced. Relying on this mutual feedback, tumorous hypoxia was largely promoted by more than 20-fold, accounting for the effective recovery of the HAP’s cytotoxicity. Consequently, our bioinspired nanodesign has demonstrated highly specific and effective antitumor potency via the biologically driven cooperation among intratumoral vascular disruption, platelet-mimicking biotaxis, cascade hypoxia amplification, and hypoxia-sensitive chemotherapy. This study offers a paradigm of correlating the therapeutic design with the physiologically occurring events to achieve better therapy performance.

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Crossref · 10.1021/acsnano.9b07330

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65 of 65 references verified0 citation errors · 0 not checkable

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  • Hypoxia occurs in the majority of solid tumors due to a poor vascular oxygen supply that is not sufficient to meet the needs of rapidly proliferating cancer cells.

    “Hypoxia occurs in the majority of solid tumors due to a poor vascular oxygen supply that is not sufficient to meet the needs of rapidly proliferating cancer cells.”

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Authors
Zhang, M., Ye, J.-J., Xia, Y., Wang, Z.-Y., Li, C.-X., Wang, X.-S., Yu, W., Song, W., Feng, J., & Zhang, X.-Z.
Affiliations
  • Wuhan University (CN)
  • Wuhan University , , ,
Corresponding author
Feng, Jun
Venue
ACS Nano
Published
2019-11-12
Volume
13
Issue
12
Pages
14230-14240
ISSN
  • 1936-0851 (ISSN-L)
  • 1936-086X
OpenAlex
W2985710337
Cited by
89
References
65
Citations by year
2026: 9 · 2025: 14 · 2024: 6 · 2023: 9 · 2022: 22 · 2021: 21 · 2020: 8
FWCI
3.62
Type
journal article
Language
en
Open access
closed
Locations
  • ACS Nano (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Ministry of Science and Technology of the People's Republic of China (2016YFB0700802)
  • National Natural Science Foundation of China (21374085, 51533006)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Keywords
tumor vasculature disruption, tumor hypoxia, hypoxia-activated prodrug, mesoporous silica nanoparticles, platelet membrane coating
MeSH terms
Tumor Hypoxia, Animals, Aorta, Blood Platelets, Cell Adhesion, Epithelial Cells, Female, Mice, Inbred BALB C, Neoplasms, Neovascularization, Pathologic, 3T3 Cells, Biomimetics, Cell Line, Tumor, Mice, Nanoparticles

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