Nanoconstructs for Advances in Photodynamic Therapy

[摘要] Nanoparticle (NP) based systems have advanced the efficacy of treating cancer by enabling selective accumulation of drugs in tumors. Photodynamic therapy (PDT) is an exceptionally promising modality for its triple selectivity in treating cancer: requiring light, oxygen, and a photosensitizer (PS). The choice of a PS can become important not only for its absorption spectrum but also its relative aggression in causing oxidative stress; clinicians may prefer one PS over another depending on the type of response required to elicit optimal treatment. We show in Chapter 2 using polyacrylamide (PAAm) hydrogel NPs that chlorin e6 (Ce6) is a much more aggressive PDT agent than the classically applied methylene blue (MB). In addition to understanding the relative aggression of a PS in PDT, design of the NP is important to optimizing both the reactive oxygen species (ROS) producing capabilities and the means of effective delivery. Previously reported 8-arm polyethylene glycol amine (8PEGA) has been used to stop heart arrhythmia via PDT from conjugated Ce6. This NP is ideal for also targeting cancer due to the optimized ROS production, ease of changing targets, and its small size that would allow for deep tumor penetration in vivo. In Chapter 3, the tumor targeting peptide F3-cys was successfully grafted to 8PEGA-Ce6 and cancer cells efficiently ablated in vitro, demonstrating promise in translation to cancer in vivo. In addition, 8PEGA was shown to be a very promising diffusion weighted magnetic resonance (MR) imaging agent for cancer due to its long T2 lifetime and high molecular weight. 8PEGA may then potentially act as an efficient agent in MR of tumors in vivo without the use of toxic heavy metal atoms. Lastly, while NP-mediated PDT has been efficiently described in treating cancer and stopping heart arrhythmia, it may also be suitable to treating cancer-like diseases, such as choroidal neovascularization (CNV). In Chapter 4, the FDA-approved dyes indocyanine green (ICG) and the PS verteporfin (VP) were successfully encapsulated in pluronic micelles and shown to ablate cancer cells with low inherent toxicity. Given the cancer-like nature of CNV, NP-mediated PDT looks like a potential modality for treatment.The presented systems are effective in evaluation of their objectives and should further encourage clinical adoption of NPs for theranostics (PDT + imaging) by being simple to prepare, purify, and exceptionally biocompatible.

[发布机构] University of Michigan

[效力级别] Theranostics

[关键词] Nanoparticles;Theranostics;Polyethylene Glycol;Photodynamic Therapy;Chemistry;Science;Chemistry