Graphene Oxide Nanoparticles Having Long Wavelength Absorbing Chlorins for Highly-Enhanced Photodynamic Therapy with Reduced Dark Toxicity

Abstract

The long wavelength absorbing photosensitizer (PS) is important in allowing deeper penetration of near-infrared light into tumor tissue for photodynamic therapy (PDT). A suitable drug delivery vehicle is important to attain a sufficient concentration of PS at the tumor site. Presently, we developed graphene oxide (GO) nanoparticles containing long wavelength absorbing PS in the form of the chlorin derivative purpurin-18-N-ethylamine (maximum absorption wavelength [λmax] 707 nm). The GO–PS complexes comprised a delivery system in which PS was loaded by covalent and noncovalent bonding on the GO nanosheet. The two GO–PS complexes were fully characterized and compared concerning their synthesis, stability, cell viability, and dark toxicity. The GO–PS complexes produced significantly-enhanced PDT activity based on excellent drug delivery effect of GO compared with PS alone. In addition, the noncovalent GO–PS complex displayed higher photoactivity, corresponding with the pH-induced release of noncovalently-bound PS from the GO complex in the acidic environment of the cells. Furthermore, the noncovalently bound GO‒PS complex had no dark toxicity, as their highly organized structure prevented GO toxicity. We describe an excellent GO complex-based delivery system with significantly enhanced PDT with long wavelength absorbing PS, as well as reduced dark toxicity as a promising cancer treatment.

Learning from Nature: Bioinspired Chlorin-Based Photosensitizers Immobilized on Carbon Materials for Combined Photodynamic and Photothermal Therapy

“…In 2019, Kang and co-authors [ 120 ] promoted the functionalization of graphene oxide with a derivative purpurin-18-N-ethylamine chlorin e6 via non-covalent and covalent methodologies ( Table 5 , entry 11). The authors evaluated the PDT efficiency of functionalized graphene oxide (non-covalent and covalent) by using the following parameters: irradiation of 2 W/cm 2 for 15 min and an incubation time of 3–24 h against human lung adenocarcinoma (A549) cells.…”

“…The functionalized graphene oxide (non-covalent and covalent) showed IC 50 values at 3, 12, and 24 h incubation of 0.69 and 0.22, 0.48 and 0.21, and 0.31 and 0.20 µM, respectively. Nevertheless, the non-covalently bound complex presented lower dark toxicity than the covalently bound complex [ 120 ]. According to the authors, the lower IC 50 values of the non-covalently bound complex may have been because of its faster delivery effect based on the rapid intracellular release of the derivative purpurin-18-N-ethylamine chlorin e6 from the graphene oxide complex [ 120 ].…”

Green Slow-Release Coated Nitrogen Fertilizer with High Water Retention Based on Core–Shell-Structured Self-Healing Supramolecular Networks

“…For dynamic covalent bonding, the recombination of cross-linked networks requires high temperature (up to 120 °C or higher) conditions. In contrast, noncovalent bonding methods, including hydrogen bonds, , ionic interactions, metal–ligand interactions, and host–guest recognition, show better commercialization prospects in SHR construction because their healing behaviors can be easily triggered by light, magnetic, pH, and thermal . Unfortunately, the mechanical properties of rubber synthesized by this method are poor, while the incorporation of common fillers such as graphene, carbon nanotubes, and cellulose nanocrystals would cause a strong interaction between the fillers and the rubber chain, thus reducing the self-healing ability of rubber materials .…”

Graphene Quantum Dots Decorated with Boron Dipyrromethene Dye Derivatives for Photodynamic Therapy

“…Functional groups imparted on graphene via oxidation (epoxy, hydroxyl, and carboxyl groups) enable easy modification with various molecules that could enhance the overall solubility, stability, and biocompatibility . Therefore, graphene and its nanoconjugates have been widely used for the delivery of PDT sensitizers both in vitro and in vivo. − Various groups demonstrated the use of nanographene as a carrier of photosensitizers to enhance the efficiency of PDT in clinical medicine, where most of them were focused on the noncovalent conjugation of drugs on the graphene surfaces. − ,− Though efficient covalent functionalization on graphene derivatives is challenging, it can substantially reduce dye leakage and associated side effects.…”