# Design and synthesis of polymer nanoparticles with pH-responsive pan-HDAC inhibitor (C5) derived from norbornene block copolymers to increase C5 solubility and improve its targeted delivery to prostate cancer sites

## TL;DR

Researchers developed pH-sensitive polymer nanoparticles to deliver a cancer drug more effectively to prostate cancer cells.

## Contribution

A novel pH-responsive nanoparticle system was designed to improve the solubility and targeted delivery of a pan-HDAC inhibitor for prostate cancer treatment.

## Key findings

- Nanoparticles with a size of 122 ± 12 nm were successfully synthesized using a norbornene-derived block copolymer.
- The nanoparticles showed enhanced drug release (61 ± 1.7%) under acidic tumor conditions compared to neutral pH.
- The system demonstrated antiproliferative effects and increased cellular uptake in prostate cancer cells.

## Abstract

This study investigated the incorporation of C5, a pan-HDAC inhibitor, into a norbornene-derived block copolymer with pH-sensitive hydrolysis (PNEG-b-P(Nor-PABA-C5)) to generate NPs for prostate cancer treatment. Amphiphilic PNEG-b-P(Nor-PABA-C5) formed NPs in aqueous environments, with hydrophobic Nor-PABA-C5 monomers in the core and hydrophilic PNEG monomers on the surface. DLS analysis showed a particle size of 122 ± 12 nm with a PDI of 0.35, confirmed by SEM and TEM. TEM imaging revealed spherical morphology, enabling the NPs to transport hydrophobic pan-HDACi drugs to PC-3 tumour sites and facilitate release through hydrolysis under acidic conditions. The NPs exhibited pH-hydrolysis characteristics, with enhanced drug release (61 ± 1.7%) at pH 6.2 compared to pH 7.4 (35 ± 0.8%). MTT assay confirmed antiproliferative effect. Analysis of FITC/(PNEG-b-P(Nor-PABA-C5)) cellular uptake showed increased absorption in prostate tumours. Live/dead cell assays showed loss of viability, with increased red fluorescence and morphological disruption at higher concentrations over 48 and 72 h.