A Near-Infrared Triggered Nanophotosensitizer Inducing Domino Effect on Mitochondrial Reactive Oxygen Species Burst for Cancer Therapy

Abstract

Photodynamic therapy (PDT) is a well-established modality for cancer therapy, which locally kills cancer cells when light irradiates a photosensitizer. However, conventional PDT is often limited by the extremely short lifespan and severely limited diffusion distance of reactive oxygen species (ROS) generated by photosensitizer, as well as the penetration depth of visible light activation. Here, we develop a near-infrared (NIR) triggered nanophotosensitizer based on mitochondria targeted titanium dioxide-coated upconversion nanoparticles for PDT against cancer. When irradiated by NIR laser, the nanophotosensitizer could produce ROS in mitochondria, which induced the domino effect on ROS burst. The overproduced ROS accumulated in mitochondria, resulting in mitochondrial collapse and irreversible cell apoptosis. Confocal fluorescence imaging indicated that the mitochondrial targeting and real-time imaging of ROS burst could be achieved in living cells. The complete removal of tumor in vivo confirmed the excellent therapeutic effect of the nanophotosensitizer.

In situquantification of diverse titanium dioxide nanoparticles unveils selective endoplasmic reticulum stress-dependent toxicity

“…Moreover, an in vivo study confirmed this observation showing that different shapes of silica NPs differentially altered physiological functions in exposed rats (Li et al 2015). We also showed that a minimal intracellular content of titanium is necessary and mandatory to induce a marked calcium homeostasis alteration, which is also cell-type dependent.…”

Nanoparticles of Titanium and Zinc Oxides as Novel Agents in Tumor Treatment: a Review

“…Therefore, UCNP-based PDT gains enhanced effectiveness in the eradication of deeper depths tumor cells [195]. This finding has been confirmed both in vitro, in human cancer cells (HeLa and MCF-7 lines) and in vivo, in female Balb/c nude mice [196, 197]. …”

ROS-Responsive Mitochondria-Targeting Blended Nanoparticles: Chemo- and Photodynamic Synergistic Therapy for Lung Cancer with On-Demand Drug Release upon Irradiation with a Single Light Source

“…Due to the short lifetime (<0.1ms) and small diffusion radius of ROS (<20 nm) in biological systems 9, the photosensitizer should be spatially close to the targeted site of action in photodynamic therapy. Mitochondria are key organelles for respiration and the primary source, approximately up to 90%, of cellular ROS generation 10-12. Hence, the mitochondria-targeting nanoparticles loaded with photosensitizers can perturb ROS homeostasis and further induce cell apoptosis, which can achieve maximized photodynamic therapeutic efficiency.…”