PUBLICATION
Co-delivery nanoparticle to overcome metastasis promoted by insufficient chemotherapy
- Authors
- Zhou, Q., Li, Y., Zhu, Y., Yu, C., Jia, H., Bao, B., Hu, H., Xiao, C., Zhang, J., Zeng, X., Wan, Y., Xu, H., Li, Z., Yang, X.
- ID
- ZDB-PUB-190507-52
- Date
- 2018
- Source
- Journal of controlled release : official journal of the Controlled Release Society 275: 67-77 (Journal)
- Registered Authors
- Jia, Haibo
- Keywords
- Co-delivery strategy, EMT, Heterogeneous drug distribution, Insufficient chemotherapy, Tumor metastasis
- MeSH Terms
-
- Animals
- Antineoplastic Agents/administration & dosage*
- Antineoplastic Agents/pharmacokinetics
- Cell Line, Tumor
- Doxorubicin/administration & dosage*
- Doxorubicin/pharmacokinetics
- Drug Carriers/administration & dosage*
- Drug Carriers/pharmacokinetics
- Drug Combinations
- Embryo, Nonmammalian
- Epithelial-Mesenchymal Transition
- Mice
- Nanoparticles/administration & dosage*
- Neoplasm Metastasis
- Neoplasms/drug therapy
- Neoplasms/metabolism
- Neoplasms/pathology
- Pyrazoles/administration & dosage*
- Pyrazoles/pharmacokinetics
- Quinolines/administration & dosage*
- Quinolines/pharmacokinetics
- Receptors, Transforming Growth Factor beta/antagonists & inhibitors
- Receptors, Transforming Growth Factor beta/metabolism
- Zebrafish
- PubMed
- 29471038 Full text @ J. Control Release
Citation
Zhou, Q., Li, Y., Zhu, Y., Yu, C., Jia, H., Bao, B., Hu, H., Xiao, C., Zhang, J., Zeng, X., Wan, Y., Xu, H., Li, Z., Yang, X. (2018) Co-delivery nanoparticle to overcome metastasis promoted by insufficient chemotherapy. Journal of controlled release : official journal of the Controlled Release Society. 275:67-77.
Abstract
Heterogeneous distribution of drug inside tumor is ubiquitous, causing regional insufficient chemotherapy, which might be the hotbed for drug resistance, tumor cell repopulation and metastasis. Herein, we verify, for the first time, that heterogeneous drug distribution induced insufficient chemotherapy would accelerate the process of epithelial mesenchymal transition (EMT), consequently resulting in the promotion of tumor metastasis. To eliminate the insufficient chemotherapy promoted metastasis, we conceived a co-delivery strategy by hydroxyethyl starch-polylactide (HES-PLA) nanoparticle, in which DOX and TGF-β receptor inhibitor, LY2157299 (LY), were administered together. In vitro and in vivo studies demonstrate that this co-delivery strategy can simultaneously suppress primary tumor and distant metastasis. Further study on immunofluorescence images of primary tumor verifies that low dose of DOX exasperates the EMT process, whereas the co-delivery nanoparticle can dramatically inhibit the progression of EMT. We reveal the impact of heterogeneous drug distribution on tumor metastasis and develop an effective co-delivery strategy to suppress the metastasis, providing guidance for clinical cancer therapy.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping