# Synergistic Effects in Matrix-Embedded Alloy Nanoclusters: Advanced Type‑I Photosensitizers for Theranostics

## TL;DR

This paper introduces a new type of nanomaterial that can both image and treat cancer cells using light, without needing oxygen.

## Contribution

The study introduces a novel class of photosensitizers based on matrix-embedded alloy nanoclusters with enhanced photodynamic therapy capabilities.

## Key findings

- CNC-AuNCs with substituted atoms show tunable emission and efficient ROS generation under light.
- The nanocomposites are biocompatible and destroy cancer cells via a Type-I photodynamic effect.
- The material's design enables theranostic applications under hypoxic tumor conditions.

## Abstract

A combination of biomedical imaging and photodynamic
therapy (PDT)
in a single nanomaterial would be a breakthrough in nanomedicine.
However, devising a single photosensitizer capable of efficient PDT
without requiring an external oxygen source under typically hypoxic
tumor conditions, combined with high photostability, biocompatibility,
and renal clearance, remains a challenge. Atomically precise ultrasmall
(<2 nm) gold nanoclusters (AuNCs) are emerging as potential multifunctional
biomedicines, encompassing imaging, diagnosis, and therapy in a single
nanoplatform. Herein, we report bioderived cellulose nanocrystal-supported
gold nanoclusters (CNC-AuNCs) with selective mono or multiheteroatom
(Ag, Pd, and Pt) substitution at the core of the nanoclusters. The
replacement of one or more gold atoms significantly modulates their
emission wavelengths, photoluminescence quantum yields, as well as
excited-state relaxation kinetics. These materials can easily penetrate
the cells, accumulating in the cytoplasm and emitting bright luminescence.
While the nanocomposites are highly biocompatible, they can produce
reactive oxygen species (ROS) through the formation of free radicals
(O2
–· and ·OH) upon
exposure of light. The synergistic effect of the light absorption
by the matrix and the diverse excited-state relaxation pathways of
the nanoclusters results in the efficient generation of ROS in variable
concentrations, ultimately leading to the complete destruction of
targeted cancer cells via Type-I photodynamic effect. The optimal
ROS efficacy combined with minimal cytotoxicity suggests a universal
strategy for developing strong PDT-I agents, paving the way for versatile
nanomaterials in theranostic applications.