Improving the Intracellular Drug Concentration in Lung Cancer Treatment through the Codelivery of Doxorubicin and miR-519c Mediated by Porous PLGA Microparticle
Abstract
Porous PLGA microparticle for the coencapsulation of doxorubicin and miR-519c was successfully constructed through the water-oil-water emulsion solvent evaporation method, using ammonium bicarbonate as a porogen. It has been characterized with high porous surface, adaptive aerodynamic diameter (<10 μm), favorable drug loading, and sustained release profile. The release supernatant exhibited a higher inhibition of cell proliferation than those from porous PLGA microparticles harboring a single component (doxorubicin or miR-519c), attributing to the enhanced induction of cell apoptosis and cell cycle arrest at S phase. Finally, the improved intracellular concentration of doxorubicin was elucidated by flow cytometry and liquid chromatography with tandem mass spectrometry, owing to the knockdown of drug transporter ABCG2 by miR-519c. Overall, the porous PLGA microparticle combining chemotherapy and gene therapy could facilitate the antitumor efficacy and reduce the side effects, and thus, it is potential to be used as a sustained release system for lung cancer treatment via pulmonary administration.
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The combination of gene therapy and chemotherapy is a potential approach to improve anti-cancer efficacy by reversing the MDR effect.
“The combination of gene therapy and chemotherapy has been considered as a potential approach to improve the anti-cancer efficacy by reversing the MDR effect.”
The combination of chemotherapy and miR-519c delivery exhibits great potential in synergistic hepatocellular carcinoma therapy by overcoming multidrug resistance and enhancing sensitivity to chemotherapeutic drugs.
“Owing to its down-regulated expression in cancer cells, the combination of chemotherapy and miR-519c delivery exhibited great potential in the synergistic HCC therapy by overcoming the MDR and further enhancing the cells’ sensitivity to chemotherapeutic drugs.22”
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- Authors
- Wu, D., Wang, C., Yang, J., Wang, H., Han, H., Zhang, A., Yang, Y., & Li, Q.
- Affiliations
- Jilin University (CN)
- Chongqing University (CN)
- Corresponding author
- Yang, Yan
- Li, Quanshun
- Venue
- Molecular Pharmaceutics
- Publisher
- American Chemical Society (ACS)
- Published
- 2016-10-06
- Volume
- 13
- Issue
- 11
- Pages
- 3925-3933
- ISSN
- 1543-8384 (ISSN-L)
- 1543-8392
- OpenAlex
- W2525369824
- Cited by
- 45
- References
- 35
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 5 · 2022: 4 · 2021: 8 · 2020: 3 · 2019: 7 · 2018: 7 · 2017: 5
- FWCI
- 2.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Jilin University (2016149)
- National Natural Science Foundation of China (81373344, 81473142, 81673502)
- Jilin Provincial Department of Education (2015469)
- Department of Science and Technology of Jilin Province (20140101140JC)
- Norman Bethune Health Science Center, Jilin University (2013105014)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- lung cancer, doxorubicin, PLGA microspheres, porous microparticles, co-encapsulation, ABCG2, pulmonary drug delivery, sustained drug release, apoptosis, cell cycle arrest, intracellular drug concentration
- MeSH terms
- A549 Cells, Polylactic Acid-Polyglycolic Acid Copolymer, Cell Cycle, Cell Survival, Doxorubicin, Humans, Lung Neoplasms, Polyglycolic Acid, Blotting, Western, Apoptosis, Lactic Acid, MicroRNAs, Caspase 3, Caspase 8, Caspase 9, Tandem Mass Spectrometry
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