Immune-modulating nanomedicines for enhanced drug delivery to non-small-cell lung cancer

Feifei Liu; Christopher B Howard; Pie Huda; Nicholas L Fletcher; Craig A Bell; Idriss Blakey; Michael Agrez; Kristofer J Thurecht

doi:10.1016/j.biomaterials.2025.123089

Immune-modulating nanomedicines for enhanced drug delivery to non-small-cell lung cancer

Biomaterials. 2025 Jan 3:317:123089. doi: 10.1016/j.biomaterials.2025.123089. Online ahead of print.

Authors

Feifei Liu¹, Christopher B Howard², Pie Huda³, Nicholas L Fletcher³, Craig A Bell³, Idriss Blakey³, Michael Agrez⁴, Kristofer J Thurecht⁵

Affiliations

¹ Centre for Advanced Imaging (CAI), Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, QLD, 4072, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Queensland, Brisbane, QLD, 4072, Australia; ARC Training Centre for Innovation in Biomedical Imaging Technology, University of Queensland, QLD, Australia.
² Centre for Advanced Imaging (CAI), Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, QLD, 4072, Australia.
³ Centre for Advanced Imaging (CAI), Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, QLD, 4072, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Queensland, Brisbane, QLD, 4072, Australia.
⁴ ARC Training Centre for Innovation in Biomedical Imaging Technology, University of Queensland, QLD, Australia; InterK Peptide Therapeutics Limited, Sydney, Australia.
⁵ Centre for Advanced Imaging (CAI), Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, QLD, 4072, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Queensland, Brisbane, QLD, 4072, Australia; ARC Training Centre for Innovation in Biomedical Imaging Technology, University of Queensland, QLD, Australia. Electronic address: [email protected].

PMID: 39793167
DOI: 10.1016/j.biomaterials.2025.123089

Abstract

Immune-modulating peptides have shown potential as novel immune-stimulating agents which enhance the secretion of anticancer cytokines in vitro. However, fast clearance from blood hampers the ability of such peptides to accumulate in the tumour and results in limited therapeutic efficacy in animal studies. To address the fast blood clearance, this work reports the development and validation of a novel polymeric nanoparticle delivery system for the efficient localization of an immunomodulating peptide in the tumour microenvironment (TME). To identify the optimal polymeric nanoparticle for this study, two types of nanoparticles were developed as either branched polymers or micelles that have similar chemical functionality but different sizes. The effect of targeting the nanomedicine to the tumour-specific antigen, glycoprotein GPC-1, was explored using a bispecific antibody (BsAb) that shows an affinity for the cell protein (GPC-1) and the nanoparticle. These systems were evaluated for targeting efficiency and tumour penetration using tumour spheroids of Lewis Lung Cancer (LLC) cells and it was shown that the targeted system significantly enhanced cell association compared to the untargeted control with minor differences in penetration. The lead micelle-peptide conjugates were identified and using in vivo allograft models they were demonstrated to have high delivery efficiency of the peptide to tumours, prolonged blood circulation, enhanced tumour accumulation and tumour suppression that was associated with immune cell recruitment to the tumour.

Keywords: Immunotherapy; Nanomedicine; Polymeric micelles.