Multifunctional micellar nanoparticles
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Polymeric micelles and nanoparticles have provided an important platform for tumor-targeted delivery of hydrophobic anticancer drugs such as doxorubicin, paclitaxel, and 5-fluorouracil. Currently, several micellar and nanoparticulate anticancer drugs have entered different phases of clinical trials. However, their clinical performance is far from reaching people’s expectation, likely due to existing challenges such as low in vivo stability, short circulation time, inefficient tumor cell uptake, and slow intracellular drug release. In recent years, we have developed different strategies, e.g. design of reduction-sensitive reversibly crosslinked biodegradable micelles and fabrication of multifunctional PLGA nanoparticles by combining functional surfactant and hyaluronic acid coatings, to solve the various delivery issues encountered by micelles, which renders markedly improved treatment efficacy and reduced systemic toxicity.

Representative Papers

1. P. Zhong, H. Meng, J. Qiu, J. Zhang, H.L. Sun, R. Cheng*, and Z.Y. Zhong*,αvβ3 Integrin-Targeted Reduction-Sensitive Micellar Mertansine Prodrug: Superb Drug Loading, Enhanced Stability, and Effective Inhibition of Melanoma Growth In Vivo, J. Control. Release 2017, DOI:10.1016/j.jconrel.2016.12.011.

2. J.T. Wu, C. Deng*, F.H. Meng, J. Zhang, H.L. Sun, and Z.Y. Zhong*, Hyaluronic acid coated PLGA nanoparticulate docetaxel effectively targets and suppresses orthotopic human lung cancer, J. Control. Release 2017,

3. Y. Fang, Y. Jiang, Zou, F.H. Meng*, J. Zhang, C. Deng, H.L. Sun and Z.Y. Zhong*, Targeted glioma chemotherapy by cyclic RGD peptide-functionalized reversibly core-crosslinked multifunctional poly(ethylene glycol)-b-poly(e-caprolactone) micelles, Acta Biomaterialia 2017,

4. J.T. Wu, J. Zhang, C. Deng*, F.H. Meng, R. Cheng, and Z.Y. Zhong*, Robust, Responsive and Targeted PLGA Anticancer Nanomedicines by Combining Reductively Cleavable Surfactant and Covalent Hyaluronic Acid Coating, ACS Appl. Mater. Interfaces 2017, DOI: 10.1021/acsami.6b15105.

5. Y.Q. Zhu, J. Zhang*, F.H. Meng, C. Deng, R. Cheng, J. Feijen*, and Z.Y. Zhong*, cRGD-functionalized reduction-sensitive shell-sheddable biodegradable micelles mediate enhanced doxorubicin delivery to human glioma xenografts in vivo, J. Control. Release 2016, 233, 29-38.

6. Y.N. Zhong, K. Goltsche, L. Cheng, F. Xie, F.H. Meng*, C. Deng, Z.Y. Zhong*, and R. Haag, Hyaluronic acid-shelled acid-activatable paclitaxel prodrug micelles effectively target and treat CD44-overexpressing human breast tumor xenografts in vivo, Biomaterials 2016, 84, 250-261.

7. R. Cheng, F.H. Meng, C. Deng, and Z.Y. Zhong*, Bioresponsive Polymeric Nanotherapeutics for Targeted Cancer Chemotherapy, Nano Today 2015, 10, 656-670.

8. W. Chen, F.H. Meng, R. Cheng, C. Deng, J. Feijen*, and Z.Y. Zhong*, Facile Construction of Dual-Bioresponsive Biodegradable Micelles with Superior Extracellular Stability and Activated Intracellular Drug Release, J. Control. Release 2015, 210, 125-133.

9. Y.N. Zhong, C. Wang, R. Cheng, L. Cheng, F.H. Meng*, Z. Liu*, and Z.Y. Zhong*, cRGD-Directed, NIR-Responsive and Robust AuNR/PEG-PCL Hybrid Nanoparticles for Targeted Chemotherapy of Glioblastoma In Vivo, J. Control. Release 2014, 195, 63-71.

10. Y.N. Zhong, F.H. Meng, C. Deng*, and Z.Y. Zhong*, Ligand-Directed Active Tumor-Targeting Polymeric Nanoparticles for Cancer Chemotherapy, Biomacromolecules 2014, 15, 1955-1969.

11. Y. Zou, Y. Song, W.J. Yang, F.H. Meng*, H.Y.Liu, and Z.Y. Zhong*, Galactose-Installed Photo-Crosslinked pH-Sensitive Degradable Micelles for Active Targeting Chemotherapy of Hepatocellular Carcinoma in Mice, J. Control. Release 2014, 193, 154-161.

12. R. Cheng, F.H. Meng, C. Deng, H.A. Klok, and Z.Y. Zhong*, Dual and Multi-Stimuli Responsive Polymeric Nanoparticles for Programmed Site-Specific Drug Delivery, Biomaterials 2013, 34, 3647-3657.

13. F.H. Meng, R. Cheng, C. Deng, and Z.Y. Zhong*, Intracellular Drug Release Nanosystems, Materials Today 2012, 15, 436-442.

14. C. Deng, Y.J. Jiang, R. Cheng, F.H. Meng, and Z.Y. Zhong*, Biodegradable Polymeric Micelles for Targeted and Controlled Anticancer Drug Delivery: Promises, Progress and Prospects, Nano Today 2012, 7, 467-480.