PUBLICATION
Targeting tumor hypoxia with stimulus-responsive nanocarriers in overcoming drug resistance and monitoring anticancer efficacy
- Authors
- Xie, Z., Guo, W., Guo, N., Huangfu, M., Liu, H., Lin, M., Xu, W., Chen, J., Wang, T., Wei, Q., Han, M., Gao, J.
- ID
- ZDB-PUB-180317-3
- Date
- 2018
- Source
- Acta biomaterialia 71: 351-362 (Journal)
- Registered Authors
- Keywords
- Hypoxia-sensitive, Penetration, Reporter, Size-shrinkable nanomedicine
- MeSH Terms
-
- A549 Cells
- Animals
- Cell Hypoxia/drug effects
- Doxorubicin*/chemistry
- Doxorubicin*/pharmacokinetics
- Doxorubicin*/pharmacology
- Drug Delivery Systems/methods*
- Drug Monitoring/methods*
- Female
- Humans
- MCF-7 Cells
- Mice
- Mice, Nude
- Nanoparticles*/chemistry
- Nanoparticles*/therapeutic use
- Neoplasms, Experimental*/drug therapy
- Neoplasms, Experimental*/metabolism
- Neoplasms, Experimental*/pathology
- RNA, Small Interfering*/chemistry
- RNA, Small Interfering*/pharmacokinetics
- RNA, Small Interfering*/pharmacology
- Reactive Oxygen Species/metabolism
- Xenograft Model Antitumor Assays*
- Zebrafish
- PubMed
- 29545193 Full text @ Acta Biomater
Citation
Xie, Z., Guo, W., Guo, N., Huangfu, M., Liu, H., Lin, M., Xu, W., Chen, J., Wang, T., Wei, Q., Han, M., Gao, J. (2018) Targeting tumor hypoxia with stimulus-responsive nanocarriers in overcoming drug resistance and monitoring anticancer efficacy. Acta biomaterialia. 71:351-362.
Abstract
Although existing nanomedicines have focused on the tumor microenvironment with the goal of improving the effectiveness of conventional chemotherapy, the penetration of a tumor's core still represents a formidable barrier for existing drug delivery systems. Therefore, a novel multifunctional hypoxia-induced size-shrinkable nanoparticle has been designed to increase the penetration of drugs, nucleic acids, or probes into tumors. This cooperative strategy relies on three aspects: (i) the responsiveness of nanoparticles to hypoxia, which shrink when triggered by low oxygen concentrations; (ii) the core of a nanoparticle involves an internal cavity and strong positive charges on the surface to deliver both doxorubicin and siRNA; and (iii) a reactive oxygen species (ROS) probe is incorporated in the nanoparticle to monitor its preliminary therapeutic response in real time, which is expected to realize the enhanced efficacy together with the ability to self-monitor the anticancer activity. A more effective inhibition of tumor growth was observed in tumor-bearing zebrafish, demonstrating the feasibility of this cooperative strategy for in vivo applications. This research highlights a promising value in delivering drugs, nucleic acids, or probes to a tumor's core for cancer imaging and treatment.
Statement of significance Hypoxia-induced chemoresistance of tumor cells still represents a formidable barrier, as it is difficult for existing drug delivery systems to penetrate the tumor hypoxia core. This study involves the hypoxia-responsive size-shrinkable nanoparticle co-delivery of DOX and siRNA to enhance the penetration of DOX deep within tumors and subsequently disturb crucial pathways of cancer development induced by hypoxia and to improve sensitization to DOX chemotherapy. Furthermore, the nanopreparation can combine the ROS probe as a self-reporting nanopreparation to realize the function of real-time feedback efficacy, which has a good application prospect in the diagnosis and treatment of cancer.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping