Doctor of Philosophy, University Of New South Wales (2018)
Bachelor of Science, University Of New South Wales (2014)
Doctor of Philosophy, University of New South Wales, Chemistry (2018)
Bachelor of Medicinal Chemistry, University of New South Wales (2014)
Samuel Yang, Postdoctoral Faculty Sponsor
Modulating the Selectivity and Stealth Properties of Ellipsoidal Polymersomes through a Multivalent Peptide Ligand Display.
Advanced healthcare materials
There is a need for improved nanomaterials to simultaneously target cancer cells and avoid non-specific clearance by phagocytes. An ellipsoidal polymersome system is developed with a unique tunable size and shape property. These particles are functionalized with in-house phage-display cell-targeting peptide to target a medulloblastoma cell line in vitro. Particle association with medulloblastoma cells is modulated by tuning the peptide ligand density on the particles. These polymersomes has low levels of association with primary human blood phagocytes. The stealth properties of the polymersomes are further improved by including the peptide targeting moiety, an effect that is likely driven by the peptide protecting the particles from binding blood plasma proteins. Overall, this ellipsoidal polymersome system provides a promising platform to explore tumor cell targeting in vivo.
View details for DOI 10.1002/adhm.202000261
View details for PubMedID 32424998
Identification of Novel Medulloblastoma Cell-Targeting Peptides for Use in Selective Chemotherapy Drug Delivery.
Journal of medicinal chemistry
2020; 63 (5): 2181–93
Medulloblastoma is a malignant brain tumor diagnosed in children. Chemotherapy has improved survival rates to approximately 70%; however, children are often left with long-term treatment side effects. New therapies that maintain a high cure rate while reducing off-target toxicity are required. We describe for the first time the use of a bacteriophage-peptide display library to identify heptapeptides that bind to medulloblastoma cells. Two heptapeptides that demonstrated high [E1-3 (1)] or low [E1-7 (2)] medulloblastoma cell binding affinity were synthesized. The potential of the peptides to deliver a therapeutic drug to medulloblastoma cells with specificity was investigated by conjugating E1-3 (1) or E1-7 (2) to doxorubicin (5). Both peptide-drug conjugates were cytotoxic to medulloblastoma cells. E1-3 doxorubicin (3) could permeabilize an in vitro blood-brain barrier and showed a marked reduction in cytotoxicity compared to free doxorubicin (5) in nontumor cells. This study provides proof-of-concept for developing peptide-drug conjugates to inhibit medulloblastoma cell growth while minimizing off-target toxicity.
View details for DOI 10.1021/acs.jmedchem.9b00851
View details for PubMedID 31347843
Multivalency in Drug Delivery-When Is It Too Much of a Good Thing?
2019; 30 (3): 503–14
Multivalency plays a large role in many biological and synthetic systems. The past 20 years of research have seen an explosion in the study of multivalent drug delivery systems based on scaffolds such as dendrimers, polymers, and other nanoparticles. The results from these studies suggest that when it comes to the number of ligands, sometimes, to quote Shakespeare, "too much of a good thing" is an apt description. Recent theoretical studies on multivalency indicate that the field may have had a misplaced emphasis on maximizing binding strength where in fact it is the selectivity of multivalent drug delivery systems that is the key to success. This Topical Review will summarize these theoretical developments. We will then illustrate how these developments can be used to rationalize the immunoresponses and drug uptake mechanisms for multivalent systems and show the path forward toward the design of better multivalent drug delivery systems.
View details for DOI 10.1021/acs.bioconjchem.8b00804
View details for Web of Science ID 000462260300002
View details for PubMedID 30742420