No abstract

Because of the limited penetration depth of visible light that generally excites most of the available photosensitizers (PSs), conventional photodynamic therapy (PDT) is limited to the treatment of superficial and flat lesions. Recently, the application of deep penetrating near-infrared (NIR) light excitable upconversion nanoparticles (UCNs) in conjunction with PDT has shown to have clear potential in the treatment of solid tumors due to its ability to penetrate thick tissue. However, various constructs developed so far have certain limitations such as poor or unstable PS loading, reducing their therapeutic efficacy and limiting their application to solution or cell-based studies. In this work, we present a method to fabricate uniform core-shell structured nanoconstruct with a thin layer of photocatalyst or PS-titanium dioxide (TiO2) stably coated on individual UCN core. Our design allows controllable and highly reproducible PS loading, preventing any leakage of PS compared to previously developed nanoconstructs, thus ensuring repeatable PDT results. Further surface modification of the developed nanoconstructs with polyethylene glycol (PEG) rendered them biocompatible, demonstrating good therapeutic efficacy both in vitro and in vivo.

Photodynamic therapy (PDT) has emerged as one of the important therapeutic options in the management of cancer and other diseases. PDT involves a tumor-localized photosensitizer (PS), which when appropriately illuminated by visible light converts oxygen into cytotoxic reactive oxygen species (ROS), that attack key structural entities within the targeted cells, ultimately resulting in necrosis or apoptosis. Though PDT is a selective modality, it can be further enhanced by combining other targeted therapeutic strategies that include the use of synthetic peptides and nanoparticles for selective delivery of photosensitizers. Another potentially promising strategy is the application of targeted therapeutics that exploit a myriad of critical pathways involved in tumorigenesis and metastasis. Vascular disrupting agents that eradicate tumor vasculature during PDT and anti-angiogenic agents that targets specific molecular pathways and prevent the formation of new blood vessels are novel therapeutic approaches that have been shown to improve treatment outcome. In addition to the well-documented mechanisms of direct cell killing and damage to the tumor vasculature, PDT can also activate the body’s immune response against tumors. Numerous pre-clinical studies and clinical observations have demonstrated the immuno-stimulatory capability of PDT. Herein, we aim to integrate the most important findings with regard to the combination of PDT and other novel targeted therapy approaches, detailing its potential in cancer photomedicine.

In the present study, quantum dot (QD) capped magnetite nanorings (NRs) with a high luminescence and magnetic vortex core have been successfully developed as a new class of magnetic-fluorescent nanoprobe. Through electrostatic interaction, cationic polyethylenimine (PEI) capped QD have been firmly graft into negatively charged magnetite NRs modified with citric acid on the surface. The obtained biocompatible multicolor QD capped magnetite NRs exhibit a much stronger magnetic resonance (MR) T2* effect where the r2* relaxivity and r2*/r1 ratio are 4 times and 110 times respectively larger than those of a commercial superparamagnetic iron oxide. The multiphoton fluorescence imaging and cell uptake of QD capped magnetite NRs are also demonstrated using MGH bladder cancer cells. In particular, these QD capped magnetite NRs can escape from endosomes and be released into the cytoplasm. The obtained results from these exploratory experiments suggest that the cell-penetrating QD capped magnetite NRs could be an excellent dual-modality nanoprobe for intracellular imaging and therapeutic applications. This work has shown great potential of the magnetic vortex core based multifunctional nanoparticle as a high performance nanoprobe for biomedical applications.

Titania-coated upconversion nanoparticles convert 980 nm to UV light for activation of coated titania to generate reactive oxygen species against cells.