Site-Specific Release of Proteins and Tumor Immunotherapy

       Compared to **all molecule drugs, protein therapeutics has the advantages of high activity, high specificity and low toxicity. Protein therapeutics has demonstrated effective treatment of various tumors and autoimmune diseases. However, protein therapeutics typically suffers a low half-life, low bioavailability, and frequent dosing. Immunogenicity is another potential issue encountered by protein drugs. We are going to develop (i) biodegradable microgels for sustained release of protein drugs such as anti-PD-1 antibody, anti-PD-L1 antibody, Herceptin, IL-2, and IL-12, to achieve highly efficient tumor immunotherapy and (ii) biodegradable nanogels and polymersomes for targeted delivery of intracellular proteins such as intracellular antibodies, granzyme B and saporin, to achieve efficient protein therapy for malignant tumors. 

Representative Papers

1)    K. Huang, Y.H. He, Z.H. Zhu, J.K. Guo, G.L. Wang, C. Deng*, and Z.Y. Zhong*, Small, Traceable, Endosome-Disrupting and Bioresponsive Click Nanogels Fabricated via Microfluidics for CD44-Targeted Cytopla**ic Delivery of Therapeutic Proteins, ACS Appl. Mater. Interfaces 2019, 11, 22171-22180.

2)    J. Chen, H. He, C. Deng*, L.C. Yin, and Z.Y. Zhong*, Saporin-Loaded CD44 and EGFR Dual-Targeted Nanogels for Potent Inhibition of Metastatic Breast Cancer In Vivo, Int. J. Pharmaceutics 2019, 560, 57-64.

3)    J. Chen, K. Huang, Q.J. Chen, C. Deng*, J. Zhang, and Z.Y. Zhong*, Tailor-Making Fluorescent Hyaluronic Acid Microgels via Combining Microfluidics and Photoclick Chemistry for Sustained and Localized Delivery of Herceptin in Tumor, ACS Appl. Mater. Interfaces 2018, 10, 3929-3937.

4)    D.C. Huang, H.L. Qian, H.S., Qiao, W. Chen*, J. Feijen, and Z.Y. Zhong*, Bioresponsive Functional Nanogels as An Emerging Platform for Cancer Therapy, Expert Opin. Drug Deliv. 2018, 15, 703-716.

5)    W.J. Yang, Y.H. Wei, J. Zhang, Z.Y. Zhong*, F.H. Meng*, Granzyme B-loaded, cell-selective penetrating and reduction-responsive polymersomes effectively inhibit progression of orthotopic human lung tumor in vivo, J. Control. Release 2018, 290, 141-149.

6)    M. Qiu, Z.Q. Zhang, Y.H. Wei, H.L. Sun, F.H. Meng, C. Deng*, and Z.Y. Zhong*, Small-Sized and Robust Chimaeric Lipopepsomes: A Simple and Functional Platform with High Protein Loading for Targeted Intracellular Delivery of Protein Toxin In Vivo, Chem. Mater. 2018, 30, 6831-6838.

7)    L. Cheng, Y. Yang, F.H. Meng*, Z.Y. Zhong*, Protein Nanotherapeutics as an Emerging Modality for Cancer Therapy, Adv. Healthcare Mater. 2018, 7, 1800685.