Photodynamic therapy (PDT) is a promising therapeutic modality for cancer. However, current protocols using bare drugs suffer from several limitations that impede its beneficial clinical effects. Here, we introduce a new approach for an efficient PDT treatment. It involves conjugating a PDT agent, meso-tetrahydroxyphenylchlorin (mTHPC) photosensitizer, to gold nanoparticles (AuNPs) that serve as carriers for the drug. AuNPs have a number of characteristics that make them highly suitable to function as drug carriers: they are biocompatible, serve as biomarkers, and function as contrast agents in vitro and in vivo. We synthesized AuNPs and covalently conjugated the mTHPC drug molecules through a linker. The resultant functional complex, AuNP-mTHPC, is a stable, soluble compound. SH-SY5Y human neuroblastoma cells were incubated with the complex, showing possible administration of higher doses of drug when conjugated to the AuNPs. Then cells were irradiated with a laser beam at 650 nm to mimic the PDT procedure. Our study shows higher rates of cell death in cells incubated with the AuNP-mTHPC complex compared to the incubation with the free drug. Using the new complex may form the basis for a better PDT strategy for a wide range of cancers.
Table of contents entryPdot nanoparticle enhance the photodynamic effect by efficient FRET to the photosensitizer. Thus, production of singlet oxygen is increased and causes irreversible damage to cancer cells. AbstractA new type of nanoparticles, Pdots, and a new methodology of photosensitization are developed to achieve a more efficient photodynamic effect in aqueous solutions and in cells. Pdots are nano-sized particles, composed of conjugated chromophoric polymers coated with PEGylated phospholipids. They exhibit good aqueous colloidal properties, a broad absorption band and a strong and narrow emission band. We show that these characteristics improve biological photosensitization, which is employed in photodynamic therapy of cancer. Amphiphilic photosensitizers such as Rose Bengal partition, non-covalently but with a high affinity, into the amphiphilic coating of the Pdots, without necessitating covalent attachment. At this close contact, very efficient fluorescence resonance energy transfer (FRET) occurs between the Pdot donor and the sensitizer acceptor. The Pdots serve as broad-band collectors of light, which is funneled, via energy transfer, to the photosensitizer. Therefore, energy transfer from them can additively assist to the activity of the acceptor's of energy. The energy transfer mechanism, strong uptake of the Pdot-sensitizer dyads by MCF-7 adenocarcinoma cells and their enhanced photosensitized killing are demonstrated.
Photodynamic therapy (PDT) and photothermal therapy (PTT) are promising therapeutic methods for cancer treatment; however, as single modality therapies, either PDT or PTT is still limited in its success rate. A dual application of both PDT and PTT, in a combined protocol, has gained immense interest. In this study, gold nanoparticles (AuNPs) were conjugated with a PDT agent, meso-tetrahydroxyphenylchlorin (mTHPC) photosensitizer, designed as nanotherapeutic agents that can activate a dual photodynamic/photothermal therapy in SH-SY5Y human neuroblastoma cells. The AuNP-mTHPC complex is biocompatible, soluble, and photostable. PDT efficiency is high because of immediate reactive oxygen species (ROS) production upon mTHPC activation by the 650-nm laser, which decreased mitochondrial membrane potential (∆ψm). Likewise, the AuNP-mTHPC complex is used as a photoabsorbing (PTA) agent for PTT, due to efficient plasmon absorption and excellent photothermal conversion characteristics of AuNPs under laser irradiation at 532 nm. Under the laser irradiation of a PDT/PTT combination, a twofold phototoxicity outcome follows, compared to PDT-only or PTT-only treatment. This indicates that PDT and PTT have synergistic effects together as a combined therapeutic method. Our study aimed at applying the AuNP-mTHPC approach as a potential treatment of cancer in the biomedical field.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.