# Antitumor Activity of Death Receptor 5‑Targeted Camptothecin-Loaded Nanoparticles in Murine Syngeneic Models

## TL;DR

This study shows that nanoparticles targeting DR5 can strongly inhibit tumor growth in mice with a working immune system.

## Contribution

The study demonstrates antitumor efficacy of DR5-targeted nanoparticles in syngeneic models for the first time.

## Key findings

- DR5-targeted nanoparticles induced apoptosis in murine cell lines in vitro.
- The nanoparticles inhibited MC38 colorectal allograft growth by over 90% in vivo.
- The results confirm DR5-targeted nanoparticles work in immunocompetent syngeneic models.

## Abstract

Death receptor 5 (DR5) is a key mediator of the extrinsic
apoptotic
pathway that is often upregulated in tumors, rendering it an attractive
target for cancer therapy. Activation of DR5 requires oligomerization,
which can be achieved through multivalent presentation of DR5 ligands
on nanoparticles. DR5-targeted nanoparticles can efficiently agonize
DR5 to inhibit the growth of human xenografts, although it remains
unclear whether these effects would translate to a syngeneic tumor
model with an immunocompetent microenvironment. Here, we develop camptothecin-loaded
polymeric nanoparticles coated with the murine DR5 antibody MD5–1
and demonstrate their pro-apoptotic effects in murine cell lines in vitro. Moreover, we show that these nanoparticles inhibit
the growth of MC38 colorectal allografts in vivo by
>90% relative to control nanoparticles. Collectively, our work
confirms
that the antitumor efficacy of DR5-targeted nanoparticles extends
to syngeneic models, paving the way for future studies to explore
their impact on tumor immunity and the surrounding microenvironment.