Related Experiment Video
Updated: Jun 3, 2025
A Comprehensive Procedure to Evaluate the In Vivo Performance of Cancer Nanomedicines
Published on: March 4, 2017
Immune-modulating nanomedicines for enhanced drug delivery to non-small-cell lung cancer
Feifei Liu1, Christopher B Howard2, Pie Huda3
1Centre 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.
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.
Insights
Researchers developed a novel nanoparticle system to improve immune-modulating peptide delivery for cancer therapy. This targeted delivery system enhances peptide accumulation in tumors, prolongs circulation, and suppresses tumor growth by recruiting immune cells.
Area of Science:
- Immunology
- Nanotechnology
- Oncology
Background:
- Immune-modulating peptides stimulate anticancer cytokine secretion but suffer from rapid blood clearance, limiting their therapeutic potential.
- Efficient delivery of immunomodulating peptides to the tumor microenvironment (TME) is crucial for effective cancer immunotherapy.
Purpose of the Study:
- To develop and validate a novel polymeric nanoparticle delivery system for enhanced localization of immune-modulating peptides in the TME.
- To compare branched polymers and micelles as nanoparticle carriers and evaluate tumor-specific targeting using a bispecific antibody (BsAb).
Main Methods:
- Development of branched polymer and micelle nanoparticles with similar chemical functionality but different sizes.
- Evaluation of nanoparticle targeting efficiency and tumor penetration using Lewis Lung Cancer (LLC) cell spheroids.
- In vivo assessment of lead micelle-peptide conjugates in allograft models for delivery efficiency, circulation time, tumor accumulation, and therapeutic efficacy.
Main Results:
- Targeted nanoparticles significantly enhanced cell association in LLC spheroids compared to untargeted controls.
- Lead micelle-peptide conjugates demonstrated high delivery efficiency to tumors, prolonged blood circulation, and enhanced tumor accumulation in vivo.
- The targeted system showed significant tumor suppression associated with increased immune cell recruitment to the tumor.
Conclusions:
- Polymeric nanoparticle systems, particularly targeted micelles, can overcome the limitations of rapid peptide clearance.
- This novel delivery system enhances the accumulation and efficacy of immune-modulating peptides in the tumor microenvironment, offering a promising strategy for cancer immunotherapy.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:27Tumor Immunotherapy