Efficacy Dependence of Photodynamic Therapy Mediated by Upconversion Nanoparticles: Subcellular Positioning and Irradiation Productivity

Abstract

Singlet oxygen ( O ), as an important kind of reactive oxygen species (ROS) and main therapeutic agent in photodynamic therapy (PDT), only have a half-life of 40 ns and an effective radius of 20 nm, which cause significant obstacles for improving PDT efficacy. In this work, novel upconversion nanoparticle (UCN)-based nanoplatforms are developed with a minimized distance between UCNs and a photosensitizer, protoporphyrin IX (PpIX), and a controllable payload of PpIX, to enhance and control ROS production. The ability of the nanoplatform to target different subcellular organelles such as cell membrane and mitochondria is demonstrated via surface modification of the nanoplatform with different targeting ligands. The results show that the mitochondria-targeting nanoplatforms result in significantly increased capability of both tumor cell killing and inhibition of tumor growth. Subcellular targeting of nanoparticles leads to the death of cancer cells in different manners. However, the efficiency of ROS generation almost have no influence on the tumor cell viability during the period of evaluation. These findings suggest that specific subcellular targeting of the nanoplatforms enhances the PDT efficacy more effectively than the increase of ROS production, and may shed light on future novel designs of effective and controllable PDT nanoplatforms.

ICG‐Sensitized NaYF4:Er Nanostructure for Theranostics

“…During the last decade, lanthanide containing inorganic luminescent nanoparticles (LNPs) that emit visible and near infrared (NIR) light under NIR excitation have played a substantial role in biomedical imaging . These dielectric nanocrystals, doped with rare‐earth ions, have generated significant interest as “nanovectors” with multiple capabilities such as biosensing, luminescent imaging, drug delivery, and theranostics . Multimodal functionality is especially important in applications of nanoagents for therapeutic purposes, when the monitoring of a therapeutic process in real time is necessary for the treatment evaluation.…”

Recent Advances in Subcellular Targeted Cancer Therapy Based on Functional Materials

“…However, the use of UV light usually suffers from limited tissue penetration (few fractions of a millimeter) as well as considerable cytotoxicity to living cells, restricting the TiO 2 ‐based PDT. Intriguingly, the integration of UCNPs which is capable to convert NIR light (700–1000 nm) into UV–vis light can just solve the above deficiency . To this end, Tang and co‐workers, for the first time, simultaneously introduced a nano‐PS (TiO 2 ) and molecule‐PS (Ce6) into a single nanoplatform for nuclear targeted PDT under one NIR laser excitation .…”

Recent Progress in Near Infrared Light Triggered Photodynamic Therapy

“…In this case, could high dose effect of ROS really result in high PDT efficacy? Very recently, Chen et al investigated the influence of PS payload or amount of ROS generation on the PDT via cellular experiments in vitro ( Figure a) . In this study, three UCNP‐based PDT with controllable payload of protoporphyrin IX were developed to adjust the efficiency of ROS generation.…”

“…a) Schematic illustration of modified microemulsion approaches for coating silica and PS on upconversion nanoparticles. Reproduced with permission . Copyright 2017, Wiley‐VCH.…”