Self-assembly of specific peptides for targeting drug resistance breast cancer
The overall goal of this research is to develop innovative approaches to treat drug resistance breast cancers. Although chemotherapy is an essential part of a successful treatment in many cases, however more than 50 % of patients with breast cancer do not benefit from chemotherapy. This is usually a result of multiple drug resistance which are either acquired during the treatment or by nature the cells are drug resistance types.
Studies have shown that cancer treatments that rely on targeting receptors can potentially result in drug resistance due to alteration or lack of these receptor. We aim to develop new approaches based on intracellular assembly of peptides that are sensitive to enzymatic pathways in cancer cells. Enzyme will trigger the self-assembly of these molecules to nanofibers and will induce cell death. The challenge is to design a molecule that will respond to enzyme in cancer cells and not normal cells to decrease systemic toxicity. The Nanomedicine lab is working on design and synthesis of a peptide that will target Eye Absent enzymes in drug resistance breast cancer.
This research will provide innovative anticancer approaches to address the problems of drug resistance and immunosuppression in cancer therapy, thus ultimately will improve the survivorship of cancer patients.
Drug Delivery Vehicles, Nanoparticles, Microcapsules, Nanofibers, and Self-assembling Peptides
The Nanomedicine lab has worked on several nanocarriers including: Self-assembling peptide and protein nanostructures, electrospun nanofibers, supercritical fluid nanostructures, and magnetic nanoparticles. Delivering drugs through targeted nanocarriers that are able to enter by cells represents an alternative approach for nonspecific drug distribution and diffusion. We have used the nanocarrier to increase drug loading capabilities, extending the drug release, external triggered release and adding targeting capabilities. The nanocarriers were utilized to achieve delivery of anticancer drugs, and anti-inflammatory drugs against Breast cancer MCF7 cells.
Peptides self-assembly from molecules to nanofibers for hydrophobic Drug Delivery
The overall goal of this project is increasing the efficiency of drug delivery in hydrophobic drugs. While a majority of drugs including anticancer drugs are hydrophobic and non-polar they have poor biodistribution and bioavailability because of their low solubility in aqueous based solutions. To overcome this problem, we work on the self-assembly of short peptide “diphenylalanine” to encapsulate non-polar drugs. The peptide self-assembles from molecules to nanofibers and have both polar and non-polar groups that can increase entrapment of non-polar drugs and their solubility.
Microcapsules with triggered drug release through alternating magnetic field
For the first time, our group developed smart release of drugs from capsules and nanofiber by using magnetic nanoparticles exposed to alternating magnetic field. In this research, the controlled release of proteins from magnetite (Fe3O4)–chitosan (CS) nanoparticles exposed to an alternating magnetic field is reported. Fe3O4–CS nanoparticles were synthesized with sodium tripolyphosphate (TPP) molecules as a crosslinking reagent. Bovine serum albumin (BSA) was used as a model protein, and its controlled release studied through the variation of the frequency of an alternating magnetic field.
Substrate-free self-assembly of peptides nano-particles through acoustic levitation
This work, for the first time, shows the possibility of a substrate-fee peptide self-assembling process, through acoustic levitation. A pair of transducers was used to create standing acoustic waves at a high frequency of 40KHz to levitate water-based droplets. Two independent control variables of the self-assembling process were considered, namely the peptide concentration level and the velocity amplitude of the acoustic wave, to understand their effects on controlling the morphology, alignment and dimensional properties of the resultant nano-structures.
Understanding the supramolecular self-assembly of biomolecules
Inspired by nature, we study the supramolecular assembly of biomolecules and investigate approaches to direct them into making smart structures. Diphenylalanine is a motif extracted from Alzheimer’s disease and capable of directing molecules into supramolecular assembly.
Effect of mechanical stretch on alignment of self-assembled peptide nanofibers to enhance MSC-to-tenocyte differentiation and maturation
Mechanical stretch is an effective strategy for enhancing stem cell behaviour and regulating stem cell fate, such as MSC-to-tencyte differentiation and maturation. In this research, for the first time, we study the effect of mechanical stretch on alignment of self-assembled peptide nanofibers, such that aligned nanofibers provide nanogrooves on PDMS substrate to enhance cell differentiation and maturation.
