All-trans retinoic acid stealth liposomes prevent the relapse of breast cancer arising from the cancer stem cells
Abstract
The relapse of cancer is mostly due to the proliferation of cancer stem cells which could not be eliminated by a standard chemotherapy. A new kind of all-trans retinoic acid stealth liposomes was developed for preventing the relapse of breast cancer and for treating the cancer in combination with a cytotoxic agent, vinorelbine stealth liposomes. In vitro studies were performed on the human breast cancer MCF-7 and MDA-MB-231 cells. In vivo evaluations were performed on the newly established relapse model with breast cancer stem cells. Results showed that the particle size of all-trans retinoic acid stealth liposomes was approximately 80nm, and the encapsulation efficiency was >90%. Breast cancer stem cells were identified with the CD44(+)/CD24(-) phenotype and characterized with properties: resistant to cytotoxic agent, stronger capability of proliferation, and stronger capability of differentiation. Inhibitory effect of all-trans retinoic acid stealth liposomes was more potent in cancer stem cells than in cancer cells. The mechanisms were defined to be two aspects: arresting breast cancer stem cells at the G(0)/G(1) phase in mitosis, and inducing the differentiation of breast cancer stem cells. The cancer relapse model was successfully established by xenografting breast cancer stem cells into NOD/SCID mice, and the formation and growth of the xenografted tumors were significantly inhibited by all-trans retinoic acid stealth liposomes. The combination therapy of all-trans retinoic acid stealth liposomes with vinorelbine stealth liposomes produced the strongest inhibitory effect to the relapse tumor model. It could be concluded that all-trans retinoic acid stealth liposomes could be used for preventing the relapse of breast cancer by differentiating cancer stem cells and arresting the cell-cycle, and for treating breast cancer as a co-therapy, thus providing a novel strategy for treating breast cancer and preventing relapse derived from breast cancer stem cells.
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ATRA liposomes and nanoparticles encapsulating simultaneously ATRA and doxorubicin have been used successfully to arrest the proliferation of breast cancer-initiating cells and to differentiate them.
“ATRA liposomes and nanoparticles encapsulating simultaneously ATRA and doxorubicin have been used successfully to arrest the proliferation of breast cancer-initiating cells and to differentiate them113,114.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [113]
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References 51 · Cited by 119
- Authors
- Li, R.-J., Ying, X., Zhang, Y., Ju, R.-J., Wang, X.-X., Yao, H.-J., Men, Y., Tian, W., Yu, Y., Zhang, L., Huang, R.-J., & Lu, W.-L.
- Affiliations
- Peking University (CN)
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2011-02
- Volume
- 149
- Issue
- 3
- Pages
- 281-291
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W1979108272
- Cited by
- 119
- References
- 51
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 6 · 2023: 5 · 2022: 8 · 2021: 9 · 2020: 12 · 2019: 6 · 2018: 7 · 2017: 11 · 2016: 7 · 2015: 10 · 2014: 6 · 2013: 8 · 2012: 12
- FWCI
- 3.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- all-trans retinoic acid, PEGylated liposomes, breast cancer recurrence, breast cancer stem cells, vinorelbine, combination therapy, CD44+/CD24- phenotype, cell cycle arrest, G0/G1 phase arrest, differentiation therapy, xenograft tumor model, MCF-7 cells, MDA-MB-231 cells
- MeSH terms
- Vinorelbine, Animals, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Cell Cycle, Female, Humans, Liposomes, Recurrence, Tretinoin, Neoplastic Stem Cells, Vinblastine, Mice, SCID, Mice
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