Preparation and Performance of Phthalocyanine @ Copper Iodide Cluster Nanoparticles for X-Ray-Induced Photodynamic Therapy

TL;DR

Researchers developed a new nanoplatform using copper iodide clusters and phthalocyanine to improve X-ray-induced photodynamic therapy for deep tumors.

Contribution

A novel biocompatible and efficient X-PDT nanoplatform using Cu-I clusters and phthalocyanine is introduced.

Findings

The CuI@PcNP platform achieved 58% efficient energy transfer between the cluster and photosensitizer.

X-ray irradiation activated the platform to generate ROS and induce cytotoxicity in HepG2 cells.

The platform achieved 77.4% tumor inhibition in a murine model with minimal toxicity.

Abstract

The efficacy of X-ray-induced photodynamic therapy (X-PDT) for deep tumors is often hindered by conventional scintillators, typically rare-earth nanoparticles plagued by long-term toxicity and suboptimal scintillation yields. Here, we introduce a copper iodide (Cu-I) cluster, Cu2I2(PPh3)2(pz), composed of earth-abundant elements, as an efficient and biocompatible energy transducer for X-PDT. A theranostic nanoplatform, CuI@PcNP, was engineered by co-encapsulating the Cu-I cluster and a phthalocyanine photosensitizer (Pc4OH) within a 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol-2000 (DSPE-PEG2K) matrix, which confers excellent physiological stability. This nano-architecture ensures nanoscale proximity between the cluster (donor) and photosensitizer (acceptor), facilitating efficient (58%) Förster resonance energy transfer (FRET) while overcoming aggregation-induced quenching. Upon X-ray irradiation, the platform effectively converted X-rays to visible light, activating Pc4OH to generate potent reactive oxygen species (ROS) and inducing significant dose-dependent cytotoxicity in human hepatocellular carcinoma (HepG2) cells. In a murine hepatoma model, enabling image-guided X-PDT that resulted in a 77.4% tumor inhibition rate with negligible systemic toxicity. Collectively, this work pioneers the integration of phthalocyanine with Cu-I clusters, providing a stable and versatile nanoplatform for image-guided X-PDT.

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