PUBLICATION
Biodegradable polymeric micelle-encapsulated doxorubicin suppresses tumor metastasis by killing circulating tumor cells
- Authors
- Deng, S., Wu, Q., Zhao, Y., Zheng, X., Wu, N., Pang, J., Li, X., Bi, C., Liu, X., Yang, L., Liu, L., Su, W., Wei, Y., Gong, C.
- ID
- ZDB-PUB-150301-15
- Date
- 2015
- Source
- Nanoscale 7(12): 5270-80 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Absorbable Implants*
- Animals
- Antibiotics, Antineoplastic/administration & dosage
- Antibiotics, Antineoplastic/chemistry
- Diffusion
- Doxorubicin/administration & dosage*
- Doxorubicin/chemistry
- Drug Implants/administration & dosage
- Drug Implants/chemistry
- Mice
- Mice, Inbred BALB C
- Nanocapsules/chemistry*
- Nanocapsules/ultrastructure
- Neoplasm Metastasis/drug therapy*
- Neoplasm Metastasis/pathology
- Neoplasm Metastasis/prevention & control*
- Neoplastic Cells, Circulating/pathology*
- Treatment Outcome
- Zebrafish
- PubMed
- 25721713 Full text @ Nanoscale
Citation
Deng, S., Wu, Q., Zhao, Y., Zheng, X., Wu, N., Pang, J., Li, X., Bi, C., Liu, X., Yang, L., Liu, L., Su, W., Wei, Y., Gong, C. (2015) Biodegradable polymeric micelle-encapsulated doxorubicin suppresses tumor metastasis by killing circulating tumor cells. Nanoscale. 7(12):5270-80.
Abstract
Circulating tumor cells (CTCs) play a crucial role in tumor metastasis, but it is rare for any chemotherapy regimen to focus on killing CTCs. Herein, we describe doxorubicin (Dox) micelles that showed anti-metastatic activity by killing CTCs. Dox micelles with a small particle size and high encapsulation efficiency were obtained using a pH-induced self-assembly method. Compared with free Dox, Dox micelles exhibited improved cytotoxicity, apoptosis induction, and cellular uptake. In addition, Dox micelles showed a sustained release behavior in vitro, and in a transgenic zebrafish model, Dox micelles exhibited a longer circulation time and lower extravasation from blood vessels into surrounding tissues. Anti-tumor and anti-metastatic activities of Dox micelles were investigated in transgenic zebrafish and mouse models. In transgenic zebrafish, Dox micelles inhibited tumor growth and prolonged the survival of tumor-bearing zebrafish. Furthermore, Dox micelles suppressed tumor metastasis by killing CTCs. In addition, improved anti-tumor and anti-metastatic activities were also confirmed in mouse tumor models, where immunofluorescent staining of tumors indicated that Dox micelles induced more apoptosis and showed fewer proliferation-positive cells. There were decreased side effects in transgenic zebrafish and mice after administration of Dox micelles. In conclusion, Dox micelles showed stronger anti-tumor and anti-metastatic activities and decreased side effects both in vitro and in vivo, which may have potential applications in cancer therapy.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping