Ashlynn Lee, Nikken Wiradharma, Zhan Yuin Ong, Chuan Yang, Majad Khan, Wei Cheng, Pei Yun Teo, Shujun Gao and Yi Yan Yang

This research focuses on the development of novel biodegradable cationic nanoparticles with a hydrophobic core and a positively charged shell for the co-delivery of drugs and genes to combat multi-drug resistant cancers. IBN researchers have designed and synthesized biodegradable amphiphilic polymers/peptides of varying degrees of positive charge. These polymers/peptides are able to self-assemble into core-shell nanoparticles in aqueous solutions before or after DNA binding. The core is able to encapsulate hydrophobic drug molecules, while the positively charged shell binds negatively charged gene/protein molecules. These nanoparticles have attained high efficiency in protein and gene delivery to various types of cells such as breast and prostate cancer cell lines as well as bone marrow stem cells. By enabling the co-delivery of drugs and genes/proteins in a single system, synergistic therapeutic effects have been achieved in suppressing tumor growth.

Amalina Bte Ebrahim Attia, Shujun Gao and Yi Yan Yang

IBN researchers have developed transparent nanostructured polymeric membranes by the polymerization of bicontinuous microemulsions using a polymerizable surfactant. The membranes have temperature-dependent swelling properties. At lower temperatures, they swell, thereby reducing adhesion and allowing the dressing to be removed from the skin easily and without pain. In addition, these transparent membranes facilitate observation of the wound, while providing a moist wound-healing environment. Therapeutics can be encapsulated within the membranes to accelerate the wound healing process. Cells can also be attached onto the thermo-sensitive membranes at 37°C, and would detach at 15°C and resume normal growth. Preliminary animal studies have demonstrated that the membranes do not induce acute systemic toxicity nor cause skin sensitization or irritation. Therefore, these membranes have a great potential to be used as wound dressing or support for cell grafting.

Shrinivas Venkataraman, Jeremy Tan, Chuan Yang, Amalina Bte Ebrahim Attia, Sangeetha Krishnamurthy, Shujun Gao and Yi Yan Yang

This research aims to develop safe polymer-based carriers with nanometer particle size and narrow size distribution, high drug loading capacity and kinetic stability to transport small molecular anticancer drugs to tumor cells based on passive and active targeting. Biodegradable polycarbonate-based block copolymers with various functional groups have been synthesized through metal-free organocatalytic ring-opening polymerization using methoxy PEG as a macroinitiator. Two platform technologies have been developed to deliver drug molecules with different structures. For example, core-shell nanoparticles formed from acid- and urea-functionalized polycarbonates provide extremely high loading capacity for drugs having amine functional group (e.g. doxorubicin) due to non-covalent interactions such as ionic, hydrogen-bonding and hydrophobic interactions between the polycarbonates and drug molecules. In another platform technology, cholesterol-functionalized polycarbonate-based block copolymers offer high loading levels for hydrophobic drugs with a rigid structure (e.g. paclitaxel and cyclosporin) with excellent kinetic stability and sub-50 nm size. In a tumor-bearing mouse model, they were observed to accumulate in leaky tumor tissue after tail vein injection. These polymers allow for further attachment of biological ligands for active tumor targeting.

Chuan Yang, Shaoqiong Liu, Nikken Wiradharma, Jeremy Tan, Zhan Yuin Ong, Yan Li, Xin Ding, Siti Nurhanna Riduan, Yugen Zhang and Yiyan Yang

Due to the increasing resistance of bacteria to conventional antibiotics, macromolecular antimicrobial peptides and polymers have received significant attention. Most conventional antibiotics do not physically damage the cell wall but penetrate into the target microorganism and act on specific targets, such as breakage of double-stranded DNA due to inhibition of DNA gyrase, blockage of cell division and triggering of the intrinsic autolysins. As a consequence, bacterial morphology is preserved and the bacteria can easily develop resistance. In contrast, our macromolecular antimicrobials do not have a specific target in microbes, and they interact with microbial membranes based on electrostatic interaction, thereby inducing damage to the microbial membranes by forming pores in the membranes. This physical action prevents microbes from developing resistance. In this project, we have designed and synthesized antimicrobial peptides and polymers so that they can self-assemble into nanostructures in aqueous solution to enhance antimicrobial efficacy. The structure of the macromolecules will be optimized in terms of hydrophobicity/hydrophilicity balance, molecular weight, counter ion and quaternization agent to achieve strong antimicrobial activities with no or minimal toxicity for applications in blood stream or skin infections, tuberculosis, surface sterilization and consumer products.