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Folic Acid-conjugated Graphene Oxide loaded with Photosensitizers for Targeting Photodynamic Therapy.

ABSTRACT: Photodynamic therapy (PDT) has emerged as an alternative and promising noninvasive treatment for cancer as well as non-cancer diseases, which involves the uptake of photosensitizers (PSs) by cancer cells followed by irradiation. The use of nanomaterials as carriers of PSs is a very promising approach to improve the development of PDT in clinical medicine. In this study, a novel folic acid-conjugated graphene oxide (GO) was strategically designed and prepared as targeting drug delivery system to achieve higher specificity. The second generation photosensitizer (PS) Chlorin e6 (Ce6) was effectively loaded into the system via hydrophobic interactions and ?-? stacking. The nanocarriers can significantly increase the accumulation of Ce6 in tumor cells and lead to a remarkable photodynamic efficacy on MGC803 cells upon irradiation. These suggested that folic acid-conjugated GO loaded Ce6 had great potential as effective drug delivery system in targeting PDT.

SUBMITTER: Huang P

PROVIDER: S-EPMC3092447 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Folic Acid-conjugated Graphene Oxide loaded with Photosensitizers for Targeting Photodynamic Therapy.

Huang Peng P Xu Cheng C Lin Jing J Wang Can C Wang Xiansong X Zhang Chunlei C Zhou Xuejiao X Guo Shouwu S Cui Daxiang D

Theranostics 20110413

Photodynamic therapy (PDT) has emerged as an alternative and promising noninvasive treatment for cancer as well as non-cancer diseases, which involves the uptake of photosensitizers (PSs) by cancer cells followed by irradiation. The use of nanomaterials as carriers of PSs is a very promising approach to improve the development of PDT in clinical medicine. In this study, a novel folic acid-conjugated graphene oxide (GO) was strategically designed and prepared as targeting drug delivery system to ...[more]

PMID: 21562631

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Project description:BackgroundCandida albicans is the most prevalent fungal pathogen of the human microbiota, causing infections ranging from superficial infections of the skin to life-threatening systemic infections. Due to the increasing occurrence of antibiotic-resistant C. albicans strains, new approaches to control this pathogen are needed. Photodynamic inactivation is an emerging alternative to treat infections based on the interactions between visible light and photosensitisers, in which pheophorbide a (PPA) is a chlorophyll-based photosensitizer that could induce cell death after light irradiation. Due to PPA's phototoxicity and low efficiency, the main challenge is to implement photosensitizer cell targeting and attacking.MethodsIn this study, PPA was conjugated with JM-phage by EDC/NHS crosslinking. UV-Vis spectra was used to determine the optimum conjugation percentages of PPA and JM-phage complex for photodynamic inactivation. After photodynamic inactivation, the efficacy of PPA-JM-phage was assessed by performing in vitro experiments, such as MTS assay, scanning electron microscopy, measurement of dysfunctional mitochondria, ROS accumulation, S cell arrest and apoptotic pathway.ResultsA single-chain variable-fragment phage (JM) with high affinity to MP65 was screened from human single-fold single-chain variable-fragment libraries and designed as a binding target for C. albicans cells. Subsequently, PPa was integrated into JM phage to generate a combined nanoscale material, which was called PPA-JM-phage. After photodynamic inactivation, the growth of C. albicans was inhibited by PPA-JM-phage and apoptosis was observed. Scanning electron microscopy analysis revealed shrinking and rupturing of C. albicans. We also found that depolarization of mitochondrial membrane potential was decreased and intracellular reactive oxygen species levels were elevated significantly in C. albicans inhibited by PPA-JM-phage. Additionally, PPA-JM-phage also lead to S-phase arrest, and metacaspase activation resulting from mitochondrial dysfunction was also found to be involved in C. albicans apoptosis.ConclusionPPa-JM-phage may induce C. albicans apoptosis through a caspase-dependent pathway and the results herein shed light on the potential application of phtototherapeutic nanostructures in fungal inactivation.

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Folic Acid-conjugated Graphene Oxide loaded with Photosensitizers for Targeting Photodynamic Therapy.

Publications

Folic Acid-conjugated Graphene Oxide loaded with Photosensitizers for Targeting Photodynamic Therapy.

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