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Enhanced fluorescence imaging guided photodynamic therapy of sinoporphyrin sodium loaded graphene oxide.

ABSTRACT: Extensive research indicates that graphene oxide (GO) can effectively deliver photosensitives (PSs) by ?-? stacking for photodynamic therapy (PDT). However, due to the tight complexes of GO and PSs, the fluorescence of PSs are often drastically quenched via an energy/charge transfer process, which limits GO-PS systems for photodiagnostics especially in fluorescence imaging. To solve this problem, we herein strategically designed and prepared a novel photo-theranostic agent based on sinoporphyrin sodium (DVDMS) loaded PEGylated GO (GO-PEG-DVDMS) with improved fluorescence property for enhanced optical imaging guided PDT. The fluorescence of loaded DVDMS is drastically enhanced via intramolecular charge transfer. Meanwhile, the GO-PEG vehicles can significantly increase the tumor accumulation efficiency of DVDMS and lead to an improved PDT efficacy as compared to DVDMS alone. The cancer theranostic capability of the as-prepared GO-PEG-DVDMS was carefully investigated both in vitro and in vivo. Most intriguingly, 100% in vivo tumor elimination was achieved by intravenous injection of GO-PEG-DVDMS (2 mg/kg of DVDMS, 50 J) without tumor recurrence, loss of body weight or other noticeable toxicity. This novel GO-PEG-DVDMS theranostics is well suited for enhanced fluorescence imaging guided PDT.

SUBMITTER: Yan X

PROVIDER: S-EPMC4280503 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Enhanced fluorescence imaging guided photodynamic therapy of sinoporphyrin sodium loaded graphene oxide.

Yan Xuefeng X Niu Gang G Lin Jing J Jin Albert J AJ Hu Hao H Tang Yuxia Y Zhang Yujie Y Wu Aiguo A Lu Jie J Zhang Shaoliang S Huang Peng P Shen Baozhong B Chen Xiaoyuan X

Biomaterials 20141215

Extensive research indicates that graphene oxide (GO) can effectively deliver photosensitives (PSs) by π-π stacking for photodynamic therapy (PDT). However, due to the tight complexes of GO and PSs, the fluorescence of PSs are often drastically quenched via an energy/charge transfer process, which limits GO-PS systems for photodiagnostics especially in fluorescence imaging. To solve this problem, we herein strategically designed and prepared a novel photo-theranostic agent based on sinoporphyrin ...[more]

PMID: 25542797

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Project description:The aim of the present study was to explore the antitumor effects of sinoporphyrin sodium (DVDMS)?mediated photodynamic therapy (PDT) and sonodynamic therapy (SDT) in glioma, and to reveal the underlying mechanisms. The uptake of DVDMS by U?118 MG cells was detected by flow cytometry (FCM). A 630?nm semiconductor laser and 1?MHz ultrasound were used to perform PDT and SDT, respectively. Cell proliferation and apoptosis were evaluated using the Cell Counting Kit?8 assay, FCM and Hoechst 33258 staining, respectively. Western blot analysis was used to detect protein expression and phosphorylation levels. BALB/c nude mice were used to establish a xenograft model of U?118 MG cells. DVDMS was injected intravenously and PDT and SDT were performed 24 h later. An in vivo imaging system was used to evaluate the fluorescence of DVDMS, to measure tumor sizes, and to evaluate the therapeutic effects. The uptake of DVDMS by U?118 MG cells was optimal after 4 h. PDT and SDT following DVDMS injection significantly inhibited the proliferation and increased apoptosis of glioma cells in vitro (P<0.05, P<0.01) respectively. In vivo, the fluorescence intensity of DVDMS was lower in the PDT and SDT groups compared with the DVDMS group, while tumor cell proliferation and weight were lower in the PDT and SDT groups than in the control group (P<0.05, P<0.01). However, there was no significant difference when laser, ultrasound or DVDMS were applied individually, compared with the control group. Hematoxylin and eosin staining suggested that both PDT and SDT induced significant apoptosis and vascular obstruction in cancer tissues. DVDMS?mediated PDT and SDT inhibited the expression levels of proliferating cell nuclear antigen (PCNA) and Bcl?xL, increased cleaved ?caspase 3 levels, and decreased the protein phosphorylation of the PI3K/AKT/mTOR signaling pathway. Changes in the expression of PCNA, and Bcl?xL and in the levels of cleaved?caspase 3 were partly reversed by N?acetyl?L?cysteine, a reactive oxygen species (ROS) scavenger. Similar results were obtained with FCM. DVDMS?mediated PDT and SDT inhibited glioma cell proliferation and induced cell apoptosis in vitro and in vivo, potentially by increasing the generation of ROS and affecting protein expression and phosphorylation levels.

Dataset Information

Enhanced fluorescence imaging guided photodynamic therapy of sinoporphyrin sodium loaded graphene oxide.

Publications

Enhanced fluorescence imaging guided photodynamic therapy of sinoporphyrin sodium loaded graphene oxide.

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