Polymeric micelles for enhanced lymphatic drug delivery to treat metastatic tumors
Abstract
Polymeric micelles have been proven to be a promising nano-sized system for drug delivery. Understanding its in vivo behaviors at the whole body, tissue and cellular levels is critical for translating this drug delivery system into clinical practice. In this study, the 14.5 nm micelles made of polyethylene glycol-phosphatidylethanolamine (PEG-PE) for delivery of doxorubicin and vinorelbine were investigated. Using confocal and two-photon microscopy imaging of live mice or tissue sections, we observed that after systemic administration, the fluorescently labeled PEG-PE micelles encapsulating doxorubicin migrated through blood vessels in entirety into the interstitial tissue, collected by lymphatic vessels, and accumulated in lymph nodes. Importantly, encapsulated drugs such as vinorelbine (Nanovin), preferentially accumulate in lymph nodes when compared to the free drugs. Moreover, the in vivo bioluminescent imaging showed that Nanovin significantly reduced lymph node metastasis rate (P<0.05) in 4 T1-luc2 murine breast tumor bearing mice. Finally, we observed that Nanovin enhanced antitumor activity against primary tumors and lung metastases while having low toxicity in various 4 T1 tumor models. This study suggests that PEG-PE micelle is a promising drug delivery system for the treatment of lymphatic metastases, and may also have important applications in other lymphatic system-related diseases.
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Drugs entrapped in micelles are protected from unexpected interactions and biodegradation in the in vivo environment, resulting in prolongation of half-life and improved efficiency.
“Moreover, drugs entrapped in micelles are protected from unexpected interactions and biodegradation in vivo environment, resulting in prolongation of the half-life and improved efficiency [49,50,51].”
From Recent Advances in Nanomicelles Delivery Systems. (2020) · cites this paper as [49]
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- Authors
- Qin, L., Zhang, F., Lu, X., Wei, X., Wang, J., Fang, X., Si, D., Wang, Y., Zhang, C., Yang, R., Liu, C., & Liang, W.
- Affiliations
- Chinese Academy of Sciences (CN)
- Zhejiang University (CN)
- Tianjin Institute of Pharmaceutical Research (China) (CN)
- Corresponding author
- Liu, Changxiao
- Liang, Wei
- ORCID
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2013-10
- Volume
- 171
- Issue
- 2
- Pages
- 133-142
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W1973417756
- Cited by
- 80
- References
- 68
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 10 · 2023: 4 · 2022: 5 · 2021: 5 · 2020: 6 · 2019: 4 · 2018: 9 · 2017: 6 · 2016: 8 · 2015: 5 · 2014: 5
- FWCI
- 2.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- Funders
- State Key Development Plan Project (2011CB707705)
- National Nature Sciences Foundation of China (81173012)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- polymeric micelles, lymphatic drug delivery, lymph node metastasis, doxorubicin, vinorelbine, breast cancer, lung metastasis, in vivo imaging, bioluminescence imaging, anticancer activity
- MeSH terms
- Vinorelbine, Animals, Antineoplastic Agents, Phytogenic, Female, Humans, Lung Neoplasms, Lymph Nodes, Lymphatic Metastasis, Mice, Inbred BALB C, Mice, Nude, Micelles, Phosphatidylethanolamines, Polyethylene Glycols, Vinblastine, Mammary Neoplasms, Animal, Drug Delivery Systems, Tumor Burden, Mice
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