Functional imaging and targeted drug delivery in mice and patient tumors with a cell nucleolus-localizing and tumor-targeting peptide

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Functional imaging and targeted drug delivery in mice and patient tumors with a cell nucleolus-localizing and tumor-targeting peptide
Title:
Functional imaging and targeted drug delivery in mice and patient tumors with a cell nucleolus-localizing and tumor-targeting peptide
Journal Title:
Biomaterials
Publication Date:
24 August 2022
Citation:
Jing, R., Wang, Q., Chen, L., Li, G., Li, R., Zhang, L., Zhang, H., Zuo, B., Seow, Y., Qiao, X., Wang, B., Xu, J., Chen, J., Song, T., & Yin, H. (2022). Functional imaging and targeted drug delivery in mice and patient tumors with a cell nucleolus-localizing and tumor-targeting peptide. Biomaterials, 289, 121758. https://doi.org/10.1016/j.biomaterials.2022.121758
Abstract:
Tumor-targeting peptides have profound clinical implications in early detection and delineation of microscopic lesions for surgical resection, and also delivery of therapeutics with reduced systemic toxicity. Here, we demonstrate that a peptide (RS), evolved from a previously reported hepatocellular carcinoma (HCC)-targeting peptide P47, enables improved HCC micrometastasis discrimination and delineation from noncancerous tissues in murine orthotopic mice and patient biopsies, with up to 21-fold contrast. Importantly, RS targets non-small cell lung (NSCLC) and colon cancers in mice and patient biopsies, with higher selectivity for highly proliferative tumor nodules. Moreover, RS localizes to cell nucleoli of HCC, NSCLC, breast, colon and cervical cancer cells and induces nucleolar stress when conjugated with chemotherapeutic Oxaliplatin (OXA) (RS-OXA), demonstrating both cellular and subcellular targeting. RS-delivered OXA elicits significant tumor retardation in orthotopic HCC mice with markedly reduced systemic toxicity compared to OXA alone. Injection of fluorescence-labeled RS enables dynamic visualization of tumor growth in RS-OXA-treated subcutaneous HCC mice. Our study demonstrates that RS targets a spectrum of tumors and localizes to cell nucleolus, thus enabling functional imaging and targeted delivery of OXA in HCC mice, and consequently provides a versatile tool for tumor imaging and targeted therapeutics.
License type:
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Funding Info:
This study was supported by National Natural Science Foundation of China (no. 82030054), Natural Science Foundation of Tianjin (20JCQNJC00580), and Tianjin Municipal 13th five-year plan (Tianjin Medical University Talent Project).
Description:
ISSN:
0142-9612
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