Assoc Prof Roger Liang

A growing body of research has confirmed that nanoparticle (NP) systems can enhance delivery of therapeutic and imaging agents as well as prevent potentially damaging systemic exposure to these agents by modifying the kinetics of their release. With a wide choice of NP materials possessing different properties and surface modification options with unique targeting agents, bespoke nanosystems have been developed for applications varying from cancer therapeutics and genetic modification to cell imaging. Although there remain many challenges for the clinical application of nanoparticles, including toxicity within the reproductive system, some of these may be overcome with the recent development of biodegradable nanoparticles that offer increased biocompatibility. In recognition of this potential, this review seeks to present recent NP research with a focus on the exciting possibilities posed by the application of biocompatible nanomaterials within the fields of male reproductive medicine, health, and research.

Background: Hyaluronic acid (HA) is a major component of extracellular matrix (ECM) and its over expression in tumor tissues contributes to the increase of interstitial fluid pressure (IFP) and hinders the penetration of nanoparticles into solid tumors. Materials and Methods: We here reported a tumoral microenvironment responsive multi-stage drug delivery system (NPs-EPI/HAase) which was formed layer by layer via electrostatic interaction with epirubicin (EPI)-loaded PEG-b-poly(2-(diisopropylamino)ethyl methacrylate)-b-poly(2-guanidinoethylmethacrylate) (mPEG-PDPA-PG, PEDG) micelles (NPs-EPI) and hyaluronidase (HAase). In this paper, we focused on the hyaluronidase-combined nanoparticles (NPs-EPI/HAase) for tumor penetration in tumor spheroid and solid tumor models in vitro and in vivo. Results: Our results showed that NPs-EPI/HAase effectively degrade the HA in ECM and facilitate deep penetration of NPs-EPI into solid tumor. Moreover, NPs-EPI mainly employed clathrin-mediated and macropinocytosis-mediated endocytic pathways for cellular uptake and were subsequently directed to the lysosomes for further drug release triggered by proton sponge effect. Compared with NPs-EPI, the HAase coating group showed an enhanced tumoral drug delivery efficacy and inhibition of tumor growth. Conclusion: Overall, our studies demonstrated that coating nanoparticles with HAase can provide a simple but efficient strategy for nano-drug carriers to enhance solid tumor penetration and chemotherapeutic efficacy.

Aim: To develop matrix metalloproteinase-responsive gelatin-albumin hybrid nanoparticles encapsulating a selective tropomyosin receptor kinase A (TrkA) inhibitor GNF-5837 (Gel-Alb-GNF HNPs) and to demonstrate their anticancer effects in breast cancer. Methods: Gel-Alb-GNF HNPs were prepared using a pH-controlled complexation process from cationic gelatin, dextran sulfate and albumin-bound GNF-5837. The anticancer activities of Gel-Alb-GNF HNPs were tested in a panel of subtype-specific breast cancer cell lines. Results: Gel-Alb-GNF HNPs (~130 nm) displayed excellent stability and matrix metalloproteinase-triggered drug release. Compared with GNF-5837 alone, Gel-Alb-GNF HNPs not only significantly enhanced the antiproliferative and anti-invasive effects but also restored the apoptosis of cancer cells. Conclusion: Gel-Alb-GNF HNPs may be adaptable for stand-alone therapies or used in combination with traditional chemotherapies for breast cancer treatment.

The use of nanotechnology has great potentials to revolutionize the future cancer diagnosis and therapy. In this context, various nanoparticles (NPs) have been developed for targeted delivery of diagnostic/therapeutic agents to the tumor sites, which thus result in greater efficacy and much less side effects. The targeting property of NPs is often achieved by functionalizing their surface with tumor-specific ligands, such as antibodies, peptides, small molecules and oligonucleotides. In this review, we will discuss recent progress in the multifunctional design of antibody-targeted NPs with a special focus on liposomal, polymeric and protein-based delivery systems.

Albendazole (ABZ), a well-established antiparasitic drug, has been shown to suppress tumor growth in a number of preclinical models of cancer. However, the low solubility of ABZ limits its use as a systemic anticancer agent. To enable systemic administration, we have formulated ABZ into albumin nanoparticles with a size range of 200-300 nm, which were cross-linked with glutaraldehyde to stabilize the nanoparticles and to introduce pH-responsive features. Drug release studies demonstrated that about 20% of ABZ was released at neutral pH within a week in comparison to 70% at slightly acidic condition (pH 5). Cellular uptake studies using ovarian cancer cells indicated that nanoparticles were internalized efficiently within 1 h of incubation. Further, cell proliferation results demonstrated that albumin nanoparticles alone showed no cytotoxicity to both normal and cancer cells. In contrast, the drug-loaded nanoparticles exhibited cellular toxicity and high killing efficacy to cancer cells compared to normal cells. Collectively, our results suggest that these albumin nanoparticles may hold great potentials as ABZ carriers for cancer therapy.