Yi Yan Yang

Bio: Yi Yan Yang is an academic researcher from Agency for Science, Technology and Research. The author has contributed to research in topics: Micelle & Cationic polymerization. The author has an hindex of 75, co-authored 358 publications receiving 19328 citations. Previous affiliations of Yi Yan Yang include National University of Singapore & Imperial College London.

Co-delivery of drugs and DNA from cationic core-shell nanoparticles self-assembled from a biodegradable copolymer.

Abstract: Non-viral gene-delivery systems are safer to use and easier to produce than viral vectors, but their comparatively low transfection efficiency has limited their applications. Co-delivery of drugs and DNA has been proposed to enhance gene expression or to achieve the synergistic/combined effect of drug and gene therapies. Attempts have been made to deliver drugs and DNA simultaneously using liposomes. Here we report cationic core-shell nanoparticles that were self-assembled from a biodegradable amphiphilic copolymer. These nanoparticles offer advantages over liposomes, as they are easier to fabricate, and are more readily subject to modulation of their size and degree of positive charge. More importantly, they achieve high gene-transfection efficiency and the possibility of co-delivering drugs and genes to the same cells. Enhanced gene transfection with the co-delivery of paclitaxel has been demonstrated by in vitro and in vivo studies. In particular, the co-delivery of paclitaxel with an interleukin-12-encoded plasmid using these nanoparticles suppressed cancer growth more efficiently than the delivery of either paclitaxel or the plasmid in a 4T1 mouse breast cancer model. Moreover, the co-delivery of paclitaxel with Bcl-2-targeted small interfering RNA (siRNA) increased cytotoxicity in MDA-MB-231 human breast cancer cells.

Self-assembled cationic peptide nanoparticles as an efficient antimicrobial agent.

Abstract: Antimicrobial cationic peptides are of interest because they can combat multi-drug-resistant microbes. Most peptides form alpha-helices or beta-sheet-like structures that can insert into and subsequently disintegrate negatively charged bacterial cell surfaces. Here, we show that a novel class of core-shell nanoparticles formed by self-assembly of an amphiphilic peptide have strong antimicrobial properties against a range of bacteria, yeasts and fungi. The nanoparticles show a high therapeutic index against Staphylococcus aureus infection in mice and are more potent than their unassembled peptide counterparts. Using Staphylococcus aureus-infected meningitis rabbits, we show that the nanoparticles can cross the blood-brain barrier and suppress bacterial growth in infected brains. Taken together, these nanoparticles are promising antimicrobial agents that can be used to treat brain infections and other infectious diseases.

Biodegradable nanostructures with selective lysis of microbial membranes

Abstract: Macromolecular antimicrobial agents such as cationic polymers and peptides have recently been under an increased level of scrutiny because they can combat multi-drug-resistant microbes. Most of these polymers are non-biodegradable and are designed to mimic the facially amphiphilic structure of peptides so that they may form a secondary structure on interaction with negatively charged microbial membranes. The resulting secondary structure can insert into and disintegrate the cell membrane after recruiting additional polymer molecules. Here, we report the first biodegradable and in vivo applicable antimicrobial polymer nanoparticles synthesized by metal-free organocatalytic ring-opening polymerization of functional cyclic carbonate. We demonstrate that the nanoparticles disrupt microbial walls/membranes selectively and efficiently, thus inhibiting the growth of Gram-positive bacteria, methicillin-resistant Staphylococcus aureus (MRSA) and fungi, without inducing significant haemolysis over a wide range of concentrations. These biodegradable nanoparticles, which can be synthesized in large quantities and at low cost, are promising as antimicrobial drugs, and can be used to treat various infectious diseases such as MRSA-associated infections, which are often linked with high mortality.

Principles of nanoparticle design for overcoming biological barriers to drug delivery

Abstract: Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery.

Cancer nanomedicine: progress, challenges and opportunities.

Abstract: The intrinsic limits of conventional cancer therapies prompted the development and application of various nanotechnologies for more effective and safer cancer treatment, herein referred to as cancer nanomedicine. Considerable technological success has been achieved in this field, but the main obstacles to nanomedicine becoming a new paradigm in cancer therapy stem from the complexities and heterogeneity of tumour biology, an incomplete understanding of nano-bio interactions and the challenges regarding chemistry, manufacturing and controls required for clinical translation and commercialization. This Review highlights the progress, challenges and opportunities in cancer nanomedicine and discusses novel engineering approaches that capitalize on our growing understanding of tumour biology and nano-bio interactions to develop more effective nanotherapeutics for cancer patients.

Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier

Abstract: In past two decades poly lactic-co-glycolic acid (PLGA) has been among the most attractive polymeric candidates used to fabricate devices for drug delivery and tissue engineering applications. PLGA is biocompatible and biodegradable, exhibits a wide range of erosion times, has tunable mechanical properties and most importantly, is a FDA approved polymer. In particular, PLGA has been extensively studied for the development of devices for controlled delivery of small molecule drugs, proteins and other macromolecules in commercial use and in research. This manuscript describes the various fabrication techniques for these devices and the factors affecting their degradation and drug release.