Related Experiment Video
Updated: Mar 21, 2026
Manufacture and Drug Delivery Applications of Silk Nanoparticles
Published on: October 8, 2016
Histone Deacetylase Inhibitors Delivery using Nanoparticles with Intrinsic Passive Tumor Targeting Properties for
Fatima El Bahhaj1, Iza Denis2, Loic Pichavant3
11. Institut de Chimie des Milieux et Matériaux de Poitiers, University of Poitiers, CNRS UMR 7285, 4 rue Michel Brunet TSA 51106, B27, Poitiers. F-86073 Poitiers cedex 9, France.
Abstract:
Fast clearance, metabolism and systemic toxicity are major limits for the clinical use of anti-cancer drugs. Histone deacetylase inhibitors (HDACi) present these defects despite displaying promising anti-tumor properties on tumor cells in vitro and in in vivo model of cancers. Specific delivery of anti-cancer drugs into the tumor should improve their clinical benefit by limiting systemic toxicity and by increasing the anti-tumor effect. In this work, we describe a simple and flexible polymeric nanoparticle platform highly targeting the tumor in vivo and triggering impressive tumor weight reduction when functionalized with HDACi. Our nanoparticles were produced by Ring-Opening Metathesis Polymerization of azido-polyethylene oxide-norbornene macromonomers and functionalized using click chemistry. Using an orthotopic model of peritoneal invasive cancer, a highly selective accumulation of the particles in the tumor was obtained. A combination of epigenetic drugs involving a pH-responsive histone deacetylase inhibitor (HDACi) polymer conjugated to these particles gave 80% reduction of tumor weight without toxicity whereas the free HDACi has no effect. Our work demonstrates that the use of a nanovector with theranostic properties leads to an optimized delivery of potent HDACi in tumor and then, to an improvement of their anti-tumor properties in vivo.
Insights
Polymeric nanoparticles deliver histone deacetylase inhibitors (HDACi) effectively to tumors, significantly reducing tumor weight without toxicity. This targeted delivery enhances anti-cancer drug efficacy and minimizes systemic side effects.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Anti-cancer drug limitations include rapid clearance, metabolism, and systemic toxicity.
- Histone deacetylase inhibitors (HDACi) show anti-tumor potential but share these clinical use defects.
- Targeted drug delivery can improve anti-cancer therapy by increasing tumor concentration and reducing systemic side effects.
Purpose of the Study:
- To develop a targeted polymeric nanoparticle platform for enhanced delivery of HDACi.
- To evaluate the in vivo anti-tumor efficacy and toxicity of HDACi-functionalized nanoparticles.
- To demonstrate improved therapeutic outcomes through targeted epigenetic drug delivery.
Main Methods:
- Polymeric nanoparticles synthesized via Ring-Opening Metathesis Polymerization of azido-polyethylene oxide-norbornene.
- Nanoparticle functionalization achieved through click chemistry.
- In vivo evaluation using an orthotopic model of peritoneal invasive cancer.
Main Results:
- Nanoparticles demonstrated highly selective accumulation within the tumor.
- Conjugation of a pH-responsive HDACi polymer to nanoparticles resulted in an 80% reduction in tumor weight.
- No observable toxicity was noted with the nanoparticle-delivered HDACi, unlike free HDACi.
Conclusions:
- The developed nanoparticle platform enables targeted delivery of potent HDACi to tumors.
- This targeted approach significantly enhances anti-tumor efficacy while mitigating systemic toxicity.
- Nanovectors with theranostic properties optimize drug delivery, improving in vivo anti-cancer treatment outcomes.
