Smart Polymersomal Drugs for Targeted Therapy of Tumors and Autoimmune Diseases

       Liposomes are the most successfully translated nanocarriers. A majority of clinically used nanomedicines such as Doxil, Marqibo, and Depocyt are based on liposomes. It is challenging, however, to develop targeted formulations based on liposomes because they have a low stability and difficulty in ligand modification. Polymersomes are very similar to liposomes. As compared to liposomes, polymersomes are much more robust, versatile and amenable to surface functionalization. Polymersomes can load not only hydrophobic drugs (e.g. docetaxel and paclitaxel) but also large amount of hydrophilic drugs (e.g. doxorubicin hydrochloride, protein, nucleic acids). We have designed a series of multifunctional biodegradable polymersomes based on polypeptides and polycarbonates and modified their surface with targeting ligands such as antibodies and peptides, to achieve high loading and targeted delivery of hydrophobic drugs (e.g. vincristine and mertansine), **all molecule hydrophilic chemical drugs (e.g. methotrexate disodium and epirubicin hydrochloride), protein and siRNA therapeutics to various tumor models such as multiple myeloma, leukemia, ovarian cancer, lung tumor, and melanoma. Macrophage-targeted polymersomal methotrexate disodium is developed to effectively treat autoimmune diseases like rheumatic arthritis. 

Representative Papers

1)    W.X. Gu, J.N. An, H. Meng, N. Yu, Y.N. Zhong, F.H. Meng*, Y. Xu*, J.L.M. Cornelissen, and Z.Y. Zhong*, CD44-Specific A6 Short Peptide Boosts Targetability and Anticancer Efficacy of Polymersomal Epirubicin to Orthotopic Human Multiple Myeloma, Adv. Mater. 2019, 1904742.

2)    Y.H. Wei, X.L. Gu, L. Cheng*, F.H. Meng*, G. Storm, and Z.Y. Zhong*, Low-toxicity Transferrin-Guided Polymersomal Doxorubicin for Potent Chemotherapy of Orthotopic Hepatocellular Carcinoma in Vivo, Acta Biomaterialia 2019, 92, 196-204.

3)    H.L. Sun, Y.F. Zhang, and Z.Y. Zhong*, Reduction-Sensitive Polymeric Nanomedicines: An Emerging Multifunctional Platform for Targeted Cancer Therapy, Adv. Drug Deliv. Rev. 2018, 132, 16-32.

4)    H.L. Sun, Y.Y. Dong, J. Feijen*, and Z.Y. Zhong*, Peptide-Directed Polymeric Nanomedicines for Precision Cancer Therapy, J. Control. Release 2018, 290, 11-27.

5)    Y. Zou, Y.F. Xia, F.H. Meng*, J. Zhang, and Z.Y. Zhong*, GE11-Directed Functional Polymersomal Doxorubicin as an Advanced Alternative to Clinical Liposomal Formulation for Ovarian Cancer Treatment, Mol. Pharmaceutics 2018, 15, 3664-3671.

6)    L. Ding, W.X. Gu, Y.F. Zhang, S.J. Yue, H.L. Sun*, J. Cornelissen, and Z.Y. Zhong*, HER2-Specific Reduction-Sensitive Immunopolymersomes with High Loading of Epirubicin for Targeted Treatment of Ovarian Tumor, Biomacromolecules 2019, 20, 3855-3863.

7)    Y.Q. Zhu, J. Feijen*, and Z.Y. Zhong*, Dual-Targeted Nanomedicines for Enhanced Tumor Treatment, Nano Today 2018, 18, 65-85.

8)    M. Qiu, H.L. Sun, F.H. Meng, R. Cheng, J. Zhang, C. Deng*, and Z.Y. Zhong*, Lipopepsomes: A novel and robust family of nano-vesicles capable of highly efficient encapsulation and tumor-targeted delivery of doxorubicin hydrochloride in vivo, J. Control. Release 2018, 272, 107-113.

9)    Y. Zhang, K.Q. Wu, H.L. Sun*, J. Zhang, J.D. Yuan, and Z.Y. Zhong*, Hyaluronic acid-shelled disulfide-crosslinked nano-polymersomes for ultrahigh-efficiency reactive encapsulation and CD44-targeted delivery of mertansine toxin, ACS Appl. Mater. Interfaces 2018, 10, 1597-1604.

10) W.J. Yang, Y.F. Xia, Y. Zou, F.H. Meng*, J. Zhang, and Z.Y. Zhong*, Bioresponsive chimaeric nano-polymersomes enable targeted and efficacious protein therapy for human lung cancers in vivo, Chem. Mater. 2017, 29, 8757-8765.

11) W.J. Yang, Y. Zou, F.H. Meng*, J. Zhang, R. Cheng, C. Deng, and Z.Y. Zhong*, Efficient and targeted suppression of human lung tumor xenografts in mice with methotrexate sodium encapsulated in all-function-in-one chimaeric polymersomes, Adv. Mater. 2016, 28, 8234-8239.