Functional Polylactides for Drug/Gene Delivery

Chong Cheng Lab

Schematic illustration of drug/gene delivery using functional PLAs

The goal of this project is to synthesize functional PLAs (polylactides) and to study their applications in therapeutic delivery.

Overview

Polylactides (PLAs) are important biodegradable polymers that have been approved by FDA for in vivo applications. However, the applications of conventional PLAs are significantly limited because of their lack of functionalities. Therefore, the goal of this project is to synthesize functional PLAs and to study their applications in therapeutic delivery. A series of research accomplishments have been made in our laboratory. First, the approaches for the preparation of a variety of functional PLAs carrying alkene, alkyne, aldehyde, amine and other groups were developed based on polymer synthesis using functional monomers and click functionalization of polymers. Second, novel brush-like polymer-drug conjugates (PDCs) and PDC-based nanoparticles with PLA-based backbone carrying anti-cancer drug moieties via labile linkages were synthesized, and biomedical assessment suggests that these PDCs may potentially serve as valid nano-therapeutics for cancer treatment. Third, the first examples of cationic PLAs (CPLAs) and pegylated CPLAs (i.e. PEG-b-CPLAs) were prepared, and their low cytotoxicity and applicability in the delivery of plasma DNA (pDNA), anticancer small interfering RNA (siRNA) and microRNA (miRNA) via nanoplex formation have been demonstrated through in vitro and in vivo studies. Fourth, unique CPLA-based nano-systems enabling both drug and gene delivery have also been achieved.

Resulting Publications

Zou, J.; Hew, C. C.; Themistou, E.; Li, Y.; Chen, C.-K.; Alexandridis, P.; Cheng, C. Adv. Mater. 2011, 23, 4274.

Chen, C.-K.; Law, W.-C.; Aalinkeel, R.; Nair, B.; Kopwitthaya, A.; Mahajan, S. D.; Reynolds, J. L.; Zou, J.; Schwartz, S. A.; Prasad, P. N.; Cheng, C. Adv. Healthcare Mater. 2012, 1, 751.

Yu, Y.; Chen, C.-K.; Law, W.-C.; Mok, J. W.; Zou, J.; Prasad, P. N.; Cheng, C. Mol. Pharmaceutics 2013, 10, 867.

Jones, C. H.; Chen, C.-K.; Jiang, M.; Fang, L.; Cheng, C.; Pfeifer, B. A. Mol. Pharmaceutics 2013, 10, 1138.

Chen, C.-K.; Jones, C. H.; Mistriotis, P.; Yu, Y.; Ma, X.; Ravikrishnan, A.; Jiang, M.; Andreadis, S. T.; Pfeifer, B. A.; Cheng, C. Biomaterials 2013, 34, 9688.

Yu, Y.; Zou, J.; Cheng, C. Polym. Chem. 2014, 5, 5854.

Yu, Y.; Chen, C.-K.; Law, W.-C.; Weinheimer, E.; Sengupta, S.; Prasad, P. N.; Cheng, C. Biomacromolecules 2014, 15, 524.

Chen, C.-K.; Law, W.-C.; Aalinkeel, R.; Nair, B.; Yu, Y.; Mahajan, S. D.; Reynolds, J. L.; Wu, J.; Li, Y.; Lai, C. K.; Tzanakakis, E. S.; Schwartz, S. A.; Prasad, P. N.; Cheng, C. Nanoscale 2014, 6, 1567.

Yu, Y.; Chen, C.-K.; Law, W.-C.; Prasad, P. N.; Cheng, C. Polym. Chem. 2015, 6, 953.

Aalinkeel, R.; Nair, B.; Chen, C. K.; Mahajan, S. D.; Reynolds, J. L.; Zhang, H.; Sun, H.; Sykes, D. E.; Chadha, K. C.; Turowski, S. G.; Bothwell, K. D.; Seshadri, M.; Cheng, C.; Schwartz, S. A. Immunology 2016, 148, 387.

Sun, H.; Yarovoy, I.; Capeling, M.; Cheng, C., Top. Curr. Chem. 2017, 375, 24.