# Polymer Nanomedicines with pH-Triggered Pirarubicin Release: Revealing the Role of Carrier Hydrophilicity and Release Kinetics in Anticancer Performance

## TL;DR

This study explores how the design of polymer nanomedicines affects their ability to release a cancer drug in response to pH, showing that linker length and hydrophobicity significantly impact treatment effectiveness.

## Contribution

The study reveals the specific impact of linker hydrophobicity and length on drug release and anticancer performance in pH-sensitive nanomedicines.

## Key findings

- Aminohexanoyl linkers improved drug release and antitumor activity compared to shorter linkers.
- The rate of drug release, controlled by linker structure, is a key factor in therapeutic efficacy.
- Polymer hydrophilicity had a lesser impact on treatment outcomes than previously assumed.

## Abstract

The therapeutic efficacy of antitumor nanomedicines is
influenced
by numerous factors, with the most critical being the selection of
an appropriate biomaterial and the use of suitable stimulus-responsive
linkers. The chosen biomaterial must be biocompatible and capable
of binding the drug via a linker that facilitates selective release
and activation of the therapeutic effect, specifically within tumor
tissue. In this study, we designed, synthesized, and compared the
physicochemical and biological properties of various polymer nanomedicines,
each bearing pirarubicin conjugated to water-soluble and biocompatible
methacrylamide-based copolymers through pH-sensitive hydrazone bonds.
Our findings indicate that the hydrophobicity and length of the linker
near the hydrazone bond are crucial factors influencing the treatment
efficacy of the nanomedicines. Conjugates with aminohexanoyl linkers
exhibited superior drug release and enhanced antitumor activity compared
with those with shorter linkers. Overall, our study highlights that
the rate of drug release, governed by the linker structure, plays
a pivotal role in therapeutic efficacy, while the hydrophilicity of
the polymer backbone has a lesser impact.