Co-delivery of paclitaxel and STAT3 siRNA by a multifunctional nanocomplex for targeted treatment of metastatic breast cancer
Abstract
Metastasis is one of the major causes of mortality in patients suffering from breast cancer. The signal transducer and activator of transcription 3 (STAT3) is closely related to cancer metastasis. Herein, a multifunctional nanocomplex was developed to simultaneously deliver paclitaxel (PTX) and STAT3 siRNA (siSTAT3) to inhibit tumor growth and prevent metastasis of breast cancer cells. PTX was encapsulated into the synthesized polyethyleneimine-polylactic acid-lipoic acid (PPL) micelle through hydrophobic interaction, while siSTAT3 was condensed onto polyethyleneimine through electrostatic interaction. The surface charge of the drug-loaded nanocomplex ( siSTAT3 PPL PTX ) was then converted to negative by coating with hyaluronic acid (HA). The multifunctional nanocomplex (HA/ siSTAT3 PPL PTX ) effectively entered CD44-overexpressed 4T1 cells via an active targeting mechanism. HA shell was degraded by the concentrated hyaluronidase in the endo/lysosome and the rapid drug release was triggered by the redox micro-environment of cytoplasm. Moreover, HA/ siSTAT3 PPL PTX showed enhanced cytotoxicity against tumor cells due to a synergistic effect of PTX and siSTAT3. The effective inhibition of tumor metastasis was confirmed by in vitro cell migration and invasion in 4T1 cells. More importantly, a superior antitumor efficacy was observed in orthotopic 4T1 tumor-bearing mice, with no side effects in major organs, and the lung metastasis was strongly inhibited in 4T1 metastasis model.…
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Chemo-gene therapy by combining PTX with STAT3 siRNA may be a practical strategy to effectively suppress tumor growth and metastasis.
“Luo et al. also verified that chemo-gene therapy by combining PTX, the first-line chemotherapeutic drug, with STAT3 siRNA may be a practical strategy to effectively suppress tumor growth and metastasis (59).”
From Small-molecule PROTAC mediates targeted protein degradation to treat STAT3-dependent epithelial cancer (2022) · cites this paper as [59]
Cites
Analysis of Circulating Tumor DNA to Monitor Metastatic Breast Cancer
Dawson, S.-J., Tsui, D. W. Y., Murtaza, M., Biggs, H., Rueda, O. M., Chin, S.-F., Dunning, M. J., Gale, D., Forshew, T., Mahler-Araujo, B., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1213261 · Cited by 2,207 · see citing works
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Jin, J., Wu, Y., Zhao, Z., Wu, Y., Zhou, Y.-D., Liu, S., Sun, Q., Yang, G., Lin, J., Nagle, D. G., et al. (2022) · JCI Insight · doi:10.1172/jci.insight.160606 · Cited by 57 · see citing works
“Luo et al. also verified that chemo-gene therapy by combining PTX, the first-line chemotherapeutic drug, with STAT3 siRNA may be a practical strategy to effectively suppress tumor growth and metastasis (59).”
- Authors
- Luo, K., Gao, Y., Yin, S., Yao, Y., Yu, H., Wang, G., & Li, J.
- Affiliations
- China Pharmaceutical University (CN)
- University of Macau (MO)
- Corresponding author
- Yu, Hua
- Li, Juan
- Venue
- Acta Biomaterialia
- Publisher
- Elsevier BV
- Published
- 2021-10
- Volume
- 134
- Pages
- 649-663
- ISSN
- 1742-7061 (ISSN-L)
- OpenAlex
- W3183225513
- Cited by
- 70
- References
- 1
- Citations by year
- 2026: 13 · 2025: 14 · 2024: 12 · 2023: 15 · 2022: 16
- FWCI
- 2.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Acta Biomaterialia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81373363)
- China Postdoctoral Science Foundation (2018M632431)
- Universidade de Macau (MYRG2018-00043-ICMS)
- National Major Science and Technology Projects of China (2015ZX09501001)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
- Keywords
- paclitaxel, co-delivery, breast cancer metastasis, hyaluronic acid targeting, CD44, redox-responsive release, 4T1 cells
- MeSH terms
- Animals, Breast Neoplasms, Female, Humans, Hyaluronic Acid, Mice, Inbred BALB C, Drug Delivery Systems, Paclitaxel, RNA, Small Interfering, Cell Line, Tumor, STAT3 Transcription Factor, Mice, Nanoparticles, Tumor Microenvironment
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