Nanoparticles for Advanced Photodynamic Therapy of Cancer

Photodynamic therapy (PDT) has been used for many years, but it is only now becoming widely accepted and utilized. Originally it was developed as a tumor therapy and some of its most successful applications are for non-malignant diseases. This article provides a broad review of different parameters used and mechanisms instituted in PDT such as photosensitizers (PS), photochemistry and photophysics, cellular localization, cellular signaling, cell metabolism and modes of cell death that operate on a cellular level, as well as photosensitizer pharmacokinetics, biodistribution, tumor localization and modes of tumor destruction. These specific cellular mechanisms are most commonly applied in PDT and for the most part are often researched and exploited. If the combination of these specific parameters and mechanisms can be optimized within PDT it could possibly be used as a suitable alternative for the treatment and management of specific cancers.

Upconversion nanoparticles (UCNPs) that emit high-energy photons upon excitation by the low-energy near-infrared (NIR) light are emerging as new optical nano-probes useful in biomedicine. Herein, we load Chlorin e6 (Ce6), a photosensitizer, on polymer-coated UCNPs, forming a UCNP-Ce6 supramolecular complex that produces singlet oxygen to kill cancer cells under NIR light. Excellent photodynamic therapy (PDT) efficacy is achieved in tumor-bearing mice upon intratumoral injection of UCNP-Ce6 and the followed NIR light exposure. It is further uncovered that UCNPs after PDT treatment are gradually cleared out from mouse organs, without rendering appreciable toxicity to the treated animals. Moreover, we demonstrate that the NIR-induced PDT based on UCNP-Ce6 exhibits a remarkably increased tissue penetration depth compared to the traditional PDT using visible excitation light, offering significantly improved treatment efficacy for tumors blocked by thick biological tissues. Our work demonstrates NIR light-induced in vivo PDT treatment of cancer in animals, and highlights the promise of UCNPs for multifunctional in vivo cancer treatment and imaging. Copyright © 2011 Elsevier Ltd. All rights reserved.

Photodynamic therapy (PDT) is an emerging cancer therapy that uses the combination of non-toxic dyes or photosensitizers (PS) and harmless visible light to produce reactive oxygen species and destroy tumors. The PS can be localized in various organelles such as mitochondria, lysosomes, endoplasmic reticulum, Golgi apparatus and plasma membranes and this sub-cellular location governs much of the signaling that occurs after PDT. There is an acute stress response that leads to changes in calcium and lipid metabolism and causes the production of cytokines and stress response mediators. Enzymes (particularly protein kinases) are activated and transcription factors are expressed. Many of the cellular responses center on mitochondria and frequently lead to induction of apoptosis by the mitochondrial pathway involving caspase activation and release of cytochrome c. Certain specific proteins (such as Bcl-2) are damaged by PDT-induced oxidation thereby increasing apoptosis, and a build-up of oxidized proteins leads to an ER-stress response that may be increased by proteasome inhibition. Autophagy plays a role in either inhibiting or enhancing cell death after PDT.