C. Cheng, H. Sun, Y. Yu, C-K Chen, J. Zou
University at Buffalo, the State University of New York,
Keywords: polylactide, cancer, drug delivery, gene delivery, drug-gene co-delivery
Summary:As an important class of biodegradable polymers, polylactides (PLAs) have been approved by FDA for clinical applications. However, conventional PLAs are lack of functionalities, and this significantly limits their applications. Therefore, in recent years we have made tremendous efforts in developing functional PLAs and investigating their applications in therapeutic delivery. Because cancer is a leading cause of death of human beings, the functional PLA-based delivery systems in our work are designed specifically for the delivery of cancer therapeutics. A series of studies have been performed in our laboratory. First, the approaches for the synthesis of a variety of functional PLAs with alkene, alkyne, aldehyde, amine, zwitterionic and other side groups have been developed. Second, several types of functional PLA-based drug delivery systems, including brush-like polymer-drug conjugates (PDCs), PDC-based nanoparticles and zwitterionic PDCs, have been prepared, and results of in vitro studies suggest that they may potentially serve as potent nano-therapeutics for cancer treatment. Third, novel cationic PLAs (CPLAs) and pegylated CPLAs (i.e. PEG-b-CPLAs) have been synthesized, and their application as transfection agent in the delivery of anticancer small interfering RNA (siRNA) has been demonstrated through in vitro and in vivo studies. Fourth, unique CPLA-based nanocapsules enabling drug delivery, gene delivery, and drug-gene co-delivery have also been achieved. These nanocapsules can effectively evade multi-drug resistance of cancer cells. Synergistic treatment effects are observed in the drug-gene co-delivery via the nanocapsules. Overall, a broad variety of functional PLA-based systems for the delivery of cancer therapeutics have been successfully prepared in our laboratory, and the preliminary biomedical results obtained from these systems encourage further biomedical studies to explore their significant potentials for cancer treatment.