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Enzyme-Responsive Modular Peptides Enhance Tumor Penetration of Quantum Dots via Charge Reversal Strategy

Dai, Qiuju, Du, Zhen, Jing, Lihong, Zhang, Rongchun, Tang, Wen·2024·ACS Applied Materials & Interfaces
DOI 10.1021/acsami.3c11500
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Abstract

Quantum dots (QDs) are colloidal semiconductor nanoparticles acting as fluorescent probes for detection, disease diagnosis, and photothermal and photodynamic therapy. However, their performance in cancer treatment is limited by inadequate tumor accumulation and penetration due to the larger size of nanoparticles compared to small molecules. To address this challenge, charge reversal nanoparticles offer an effective strategy to prolong blood circulation time and achieve enhanced endocytosis and tumor penetration. In this study, we leveraged the overexpressed γ-glutamyl transpeptidase (GGT) in many human tumors and developed a library of modular peptides to serve as water-soluble surface ligands of QDs. We successfully transferred the QDs from the organic phase to the aqueous phase within 5 min. And through systematic tuning of the peptide sequence, we optimized the fluorescent stability of QDs and their charge reversal behavior in response to GGT. The resulting optimal peptide stabilized QDs in aqueous solution with a high fluorescent retention rate of 93% after three months and realized the surface charge reversal of QDs triggered by GGT in vitro. The binding between the peptide and QD surface was investigated by using saturation transfer differential nuclear magnetic resonance (STD NMR). Thanks to its charge reversal ability, the GGT-responsive QDs exhibited enhanced cellular uptake in GGT-expressing cancer cells and deeper penetration in the 3D multicellular spheroids. This…

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Metadata

Authors
Dai, Q., Du, Z., Jing, L., Zhang, R., & Tang, W.
Venue
ACS Applied Materials & Interfaces
Publisher
American Chemical Society (ACS)
Published
2024-01-27
Volume
16
Issue
5
Pages
6208-6220
ISSN
  • 1944-8244
  • 1944-8252
DOI
10.1021/acsami.3c11500
Cited by
17
References
2
Language
en
Licence
Funders
  • Youth Innovation Promotion Association of the Chinese Academy of Sciences (Y2022017)
  • National Natural Science Foundation of China (22177115, 22201081)
  • Natural Science Foundation of Guangdong Province (2022A1515011443)
  • Key Laboratory of Polymer Materials Design and Synthesis of Biomedical Functions Oriented to the Petroleum and Chemical Industry, Soochow University (SDHY2201)

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