# Antitumor Efficacy and Immunomodulation of H‑Ferritin Nanocaged Doxorubicin for Triple Negative Breast Cancer

## TL;DR

This study shows that HFn-Dox, a nanocarrier-based doxorubicin formulation, is more effective and safer than traditional forms for treating triple-negative breast cancer.

## Contribution

The study demonstrates HFn-Dox's superior antitumor efficacy and immunomodulatory effects in preclinical models of TNBC.

## Key findings

- HFn-Dox significantly suppressed tumor growth and metastasis in TNBC models.
- HFn-Dox showed lower cardiotoxicity compared to free doxorubicin and Lipo-Dox.
- HFn-Dox enhanced immune cell infiltration and preserved T cell viability in vitro.

## Abstract

Triple-negative breast cancer (TNBC) remains a major
therapeutic
challenge due to its aggressiveness and lack of targeted treatment
options. Ferritin-encapsulated doxorubicin (HFn-Dox) is a nanocarrier-based
formulation with documented tumor targeting activity and antitumor
potential. In this study, we advance its clinical relevance by evaluating
the HFn-Dox efficacy and toxicity profile at therapeutic dosing in
patient-derived xenograft (PDX) and syngeneic TNBC models. HFn-Dox
significantly outperformed free Dox by suppressing tumor growth and
reducing metastatic spreading in both the models. When compared with
free Dox and the clinically approved pegylated liposomal doxorubicin
(Lipo-Dox), HFn-Dox also displayed a more favorable cardiotoxicity
profile, which allowed dose intensification without compromising safety.
Additionally, HFn-Dox modulated the tumor immune microenvironment
in immunocompetent mice by enhancing intratumoral infiltration of
Tlymphocytes and M1 macrophage polarization. In vitro, HFn-Dox preserved
the T cell viability and prevented exhaustion. It also promoted the
activation of macrophages and dendritic cells, contrasting with the
immunosuppressive effects of free Dox. Altogether, our results demonstrate
that HFn-Dox can increase the therapeutic index of doxorubicin by
combining improved tumor delivery, reduced off-target toxicity, and
immune system preservation. These features support the translational
potential of HFn-Dox as a safer and more effective nanochemotherapy
for TNBC.