Enhanced Photodynamic Properties of Graphene Quantum Dot Conjugated Ce6 Nanoparticles for Targeted Cancer Therapy and Imaging

Abstract

In this study, we report the enhanced photodynamic therapeutic (PDT) activity of Chlorin e6 (Ce6)-loaded graphene quantum dots (GQDs). GQDs reinforced the Ce6 loading, solubility, and fluorescence in aqueous media and enhanced ROS production and cancer cell death. This GQDs conjugated Ce6 could be a good platform for imaging-guided cancer therapy. Keywords: Graphene quantum dot (GQD) | Photodynamic therapy | Reactive oxygen species (ROS)Photodynamic therapy (PDT) is a light-sensitive cancer therapy that employs the cooperative interactions between light and photosensitizer (PS) to generate reactive oxygen species (ROS) and promote tumor suppression.1 In general, PDT involves in the systemic, local, or topical administration of a nontoxic drug or dye known as PS at the targeted site, followed by selective illumination with the appropriate wavelength and power of light.2,3 During this process, PS absorbs the appropriate wavelength of light and reaches the excited state. While returning to the ground state, PS transfers its energy to the local oxygen molecules and aids in the production of ROS. The ROS thus produced can activate pro apoptotic signals and aid in programmed cancer cell death and complete tumor destruction. 4 In particular, the second-generation PS like Chlorin e6 (Ce6) have gained significant attention in PDT as they possess high ROS production activity with minimal dark toxicity.5 However, the poor biological stability, undesirable pharmacokinetics, non-specific biodistribution, and lack of targeting specificity of Ce6 impede their applications to clinical settings.6 Several carriers including iron oxide nanoclusters, 7 gold nanoparticles, 8 graphene oxide, 4 graphene quantum dots, 9 and silica nanoparticles have been used to improve the stability and therapeutic outcomes of these PS. Chen et al. introduced the concept of photodynamic molecular beacon where 1 O 2 quencher and PS are placed in close proximity by conjugating to the diseasespecific linker and combined the two principles of fluorescence resonance energy transfer and photodynamic therapy. Graphene quantum dots (GQDs) are 0D nanomaterials that gained significant attention in imaging-guided cancer therapy. Their quantum confinement and edge effect characteristics imparted GQDs with enhanced photostability, tunable photoluminescence, and electrochemiluminescence properties. 1113 Moreover, these materials are biocompatible, non-toxic, and can easily be functioned with diverse drug and biomolecules.14 In addition, GQDs possess higher surface area and have the ability to initiate ππ interactions with the aromatic drug molecules and improve their aqueous stability and solubility.1517 Nanosized GQDs can not only accumulate in the tumor site, generating ROS via a multistage sensitization process, but also generate photothermal properties and promote tumor suppression. 18Here, we first conjugated Ce6 to hyaluronic acid (HA) and further loaded over GQDs to develop targeted, imaging-guided photodynamic therapy to treat cancer (Scheme 1). HA is a ...

Hyaluronic Acid-Conjugated Carbon Nanomaterials for Enhanced Tumour Targeting Ability

“…Photodynamic therapy is a light-sensitive cancer therapy that employs the cooperative interaction between light and photosensitiser to promote tumour suppression [ 95 , 96 ]. The cancerous cell is eventually killed under the correct conditions post-irradiation, as the photosensitizer overheats and essentially is self-terminated along with the neighbouring cells overexpressing hyaluronic acid receptors.…”

Graphene Quantum Dots for Optical Bioimaging

“…It displayed N‐binding dependent ROS generation and the PDT therapeutic effects. Nafiujjaman et al conjugated Ce6 to HA and further loaded it onto GQDs to develop a cancer cell‐targeted, imaging‐guided PDT nanosystems . The as‐prepared GQD‐HA‐Ce6 nanoparticles possessed a good biocompatibility, enhanced photosensitizer imaging detection, and excellent PDT under laser irradiation.…”

Synthesis, Properties, and Biological Applications of Metallic Alloy Nanoparticles

“…Quantum dots are semiconductors with fluorescence properties that allow them to be used for real time drug delivery and as photosensitizers. With surface modification using tumor recognized molecules and drugs, quantum dots can move to target tumors and act as a supporting energetic agent in photodynamic therapy, a method that combines light and photosensitizers to generate oxygen species and promote tumor suppression [ 254 , 260 , 261 , 262 ]. Quantum dots are frequently used in a complex like with graphene and photosensitizer such as chlorin e6 [ 261 , 263 ].…”

“…With surface modification using tumor recognized molecules and drugs, quantum dots can move to target tumors and act as a supporting energetic agent in photodynamic therapy, a method that combines light and photosensitizers to generate oxygen species and promote tumor suppression [ 254 , 260 , 261 , 262 ]. Quantum dots are frequently used in a complex like with graphene and photosensitizer such as chlorin e6 [ 261 , 263 ]. Martinenko et al reported that the complex ZnSe/ZnS quantum dots with chlorin e6 showed two-fold enhancement of photodynamic destruction in Ehrlich ascites carcinoma cells compared to that with free chlorin e6 molecules, and approximately 50% fluorescence resonance energy transfer from QDs to the chlorin e6 molecules [ 264 ].…”