# Folate-targeted gold nanoparticles for doxorubicin delivery in tumor spheroids

## TL;DR

This study develops gold nanoparticles that deliver doxorubicin specifically to cancer cells, improving treatment effectiveness and reducing side effects.

## Contribution

Folate-targeted gold nanoparticles with a pH-sensitive doxorubicin prodrug are introduced for enhanced cancer therapy.

## Key findings

- Nanoparticles released 100% of doxorubicin at pH 5 but only 13% at pH 7.4.
- Folate decoration improved drug delivery to folate receptor-positive cancer cells.
- Folated nanoparticles reduced spheroid volume more effectively than non-targeted ones.

## Abstract

Targeted drug delivery systems represent a promising strategy for enhancing the efficacy and specificity of cancer therapy. In this study, 35 nm folate-targeted gold nanoparticles are presented as nanoparticle–drug conjugates obtained by anchoring on their surface lipoyl terminating doxorubicin prodrug (proDoxo) releasable at the endolysosomal acidic pH to prevent off-site toxic effects. Colloidal stable nanoparticles with a density of proDoxo up to 1000 molecules/particle and 2 kDa mPEG-SH coating were obtained. At pH 5, Doxo was completely released from the nanoparticles in 5 days while only 13% was released over the same period at pH 7.4. The nanoparticle decoration with folic acid as a targeting agent bestowed nanosystems with selective drug delivery to folate receptor (FR)-overexpressing cancer cells and controlled intracellular release. This led to enhanced cancer cell killing by folated nanoparticles compared to their nontargeted counterparts. Moreover, folated nanoparticles were found to distribute more homogeneously inside KBFR+ cancer cell spheroids than non-targeted nanoparticles, resulting in higher spheroid volume reduction.

Folate-targeted gold nanoparticles decorated with a pH-releasable doxorubicin prodrug achieve selective and controlled drug release and enhanced folate receptor (FR)-positive cancer cell killing. With up to 1000 doxorubicin/particle, PEG coatings ensured remarkable colloidal stability. Folate decoration promotes homogeneous distribution into FR-positive KB cell spheroids, yielding superior therapeutic efficacy over non-targeted systems and lowering anticancer drug toxicity.