(292g) Award Submission: Design and Tailoring the Self-Assembly of Amphiphilic Oligopeptide Nanostructures as Versatile Biomaterials for Delivery of Anticancer Drugs, Genes, or Both, for Improved Cancer Treatment | AIChE

(292g) Award Submission: Design and Tailoring the Self-Assembly of Amphiphilic Oligopeptide Nanostructures as Versatile Biomaterials for Delivery of Anticancer Drugs, Genes, or Both, for Improved Cancer Treatment

Authors 

Wiradharma, N. - Presenter, Institute of Bioengineering and Nanotechnology; National University of Singapore
Tong, Y. W. - Presenter, National University of Singapore
Yang, Y. Y. - Presenter, Institute of Bioengineering and Nanotechnology


The number of clinical trials for gene therapy has increased world-wide, with 66.5% of its target were aimed at cancer therapy.As opposed to viral based delivery vector, cationic polymers offers benefits like easy manufacturing and scale up, low immunogenicity and high amount of genes it can carry. One of the major barriers in cancer treatments is drug resistance, which has lately been suggested to be the result of chromosomal alterations leading to genetic malfunctions in cancer cells. As such, delivery of siRNA or anticancer genes have been attempted to sensitize cancer cells towards anticancer drug treatments.

In this study, we had designed various amphiphilic oligopeptides with different blocks to achieve different self-assembly properties desirable for different types of therapeutic cargo molecules. Versatility of oligopeptide to form a novel class of biodegradable biomaterials as carriers of therapeutics were demonstrated by tailoring different types of amino acids in the design of the carrier molecules. The oligopeptides designed contained both hydrophobic and hydrophilic amino acids to provide driving force for micellar nanoparticle formations. Various types of hydrophobic amino acids with different degrees of hydrophobicity were used to tailor different properties and strength of the hydrophobic interactions in forming the nanoparticles. On the other hand, the compositions of the amino acids in the hydrophilic block were designed based on the different therapeutic cargos to be delivered. Lysine residue was chosen to provide gene binding and protection, histidine residue was chosen to provide endosomal escape mechanism upon uptake of nanoparticles, and Glycine or Serine residues were used as neutral hydrophilic shell to encapsulate and solubilize hydrophobic drugs inside the core. Tailoring the amino acids was also shown to affect the particle stability, drug encapsulation and release properties, but without affecting gene binding capacity. This allows the use of the oligopeptide nanostructures for simultaneous delivery of drugs and genes to achieve synergistic effect for cancer treatment.