Amal J. Sivaram1, 2, Craig Bell1, 2, Kristofer J. Thurecht*1, 2

 

1Australian Institute of Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, Australia
2
Centre for Advanced Imaging, The University of Queensland, Brisbane, Queensland, Australia and the ARC Centre of Excellence in Convergent Bio-Nano Science and Technology
a.jsivaram@uqconnect.edu.au
k.thurecht@uq.edu.net.au +61733460344

 

The ability to integrate nanomaterials with biological components has led to the development of new generation devices, diagnostic tools and biotechnology-derived therapeutic-enhancing products.1 However, in order to optimise the design of these hybrid bio-nanomaterials, it is essential to understand the physicochemical properties of these materials, the function of each component and their interactions on a molecular level.2 Research to date has established some general rules for designing new nanomaterials for drug delivery, with respect to the size, surface moieties etc..3 However, these generalised rules seldom transfer between the in vitro to in vivo and there is no clear methodology for optimising targeting approaches for drug delivery vehicles. In this presentation, we report on developing an amphiphilic protein-polymer conjugate for assembly into targeted micellar structures. By controlling the protein density of mixed micelles, the aim is to address key questions relating to optimisation of their function: 1) the effect of ligand density and 2) the effect of multiple ligand binding to surface receptors. This approach gives fundamental insight into how these different parameters affect the rate and mechanistic pathways into cells, as well as a method to probe the intricate interplay between increased targeting efficiency versus the subsequent immune response. In summary, we have developed targeted stealth nanoparticles using conjugates of polyethylene glycol (PEG) and antibodies with a thermo-responsive polymer. By varying the ratios of these components, targeted stealth nanoparticles of different antibody content were formed by self-assembly. In vitro and in vivo analysis of these different systems provided a better understanding on the influence of both antibody and PEG density on the targeting and clearance mechanisms of the nanoparticle.

[1] S Xu, B.Z. Olenyuk, C.T. Okamoto, S. F. Hamm-Alvarez, Advanced drug delivery reviews, 2013, 65(1), 121-138.

2 Lundqvist, M., Nanoparticles: tracking protein corona over time. Nature nanotechnology, 2013, 8 (10), 701-702.

3 A. V. Fuchs, B. W. C. Tse, A. K. Pearce, M.-C. Yeh, N. L. Fletcher, S. S. Huang, W. D. Heston, A. K. Whittaker, P. J. Russell and K. J. Thurecht, Biomacromolecules, 2015, 16, 3235-3247.

 

Biographic Details

Name: Amal J Sivaram

Title: Mr

Affiliation, Country:  AIBN, The University of Queensland, Australia

Phone: +61449247481 E-mail: a.jsivaram@uqconnect.edu.au

Research interests: Cancer nanomedicine, Drug delivery, Smart materials.