Poly(ethylene glycol) conjugated nano-graphene oxide

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Introduction
Photodynamic therapy (PDT) of cancer involves the delivery of photosensitive molecules, designated as photosensitizers (PS), into the cancer tissue or cells. In the process of PDT, PSs may be activated by irradiation to transfer energy to the oxygen molecules at these sites, resulting in the formation of reactive oxygen species [1, 2], such as singlet oxygen (1O2) and free radicals. These cytotoxic species thus cause irreversible damages to cancer tissues or cells [3]. Several types of phthalocyanine or porphyrin-based photosensitive agents have been developed for PDT [4–6]. Among these agents, zinc phthalocyanine (ZnPc) is one of the most promising PSs for PDT as a result of its relatively high optical absorption in the domain of the phototherapeutic win*Corresponding author (email: shid@; yongyong_li@)

© Science China Press and Springer-Verlag Berlin Heidelberg 2010
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DONG HaiQing, et al.
SHale Waihona Puke i China ChemNovember (2010) Vol.53 No.11
A novel methoxy-poly(ethylene glycol) modified nano-graphene oxide (NGO-mPEG) was designed and synthesized as a photosensitizer (PS) carrier for photodynamic therapy of cancer. NGO with a size below 200 nm was prepared using a modified Hummers’ method. NGO was observed by AFM to exhibit a structure with single-layer graphene oxide sheets down to a few nanometers in height. Hydrophilic mPEG conjugation of NGO (NGO-mPEG) was found to enhance solubility in cell culture media. No apparent cytotoxicity of the NGO-mPEG was observed towards MCF-7 carcinoma cell line. Zinc phthalocyanine (ZnPc), a photosensitizer for photodynamic therapy, was loaded in the NGO-PEG through - stacking and hydrophobic interactions, with the drug loading efficiency up to 14 wt%. Hydrophobic ZnPc was internalized in MCF-7 cells, exhibiting a pronounced phototoxicity in the cells under Xe light irradiation. The results indicate a great potential of NGO-mPEG for photodynamic therapy of cancer. nano-graphene oxide, photodynamic therapy, photosensitizer, drug delivery, biomedical application
dow (600–800 nm), compared to other porphyrin-based PSs [7, 8]. However, ZnPc is highly hydrophobic and prone to self-aggregation in aqueous solutions. This leads to drastic decrease in the photosensitizing efficiency of ZnPc [9]. High hydrophobicity also leads to poor bioavailability and unfavorable biodistribution in the normal living tissue [10, 11]. To address these issues, several pharmaceutical formulations have been developed for effective delivery of PSs. In particular, polymeric micelles and liposomes, such as Pluronic123 and dipalmitoyl phosphatidylcholine, were studied extensively as PS-nanocarriers for PDT [12, 13]. However, the loading efficiencies of these systems (generally 1–2 wt%) are relatively low, most likely due to poor compatibility between PSs and these carriers. Therefore, it is essential to explore new PS-nanocarries for the success of PDT. In recent years, graphene, whose structure features a singleatom thickness sheet of hexagonally arrayed sp2-bonded carbon atoms, has received considerable attention [14]. It
offers fascinating electronic, thermal, and mechanical properties that are potentially useful for advanced electronics, membranes, and nanocomposites [15–18]. Graphene interacts with PSs via - stacking and hydrophobic interactions. Its oxide derivative (graphene oxide) is highly dispersible in aqueous solution. These characteristics indicate that graphene oxides may be potentially useful for biomedical applications, e.g., in drug delivery. Several groups including Dai [19] and Chen [20] have employed graphene oxides as nanocarriers for anticancer drug delivery. For instance, Dai et al. reported on the in vitro cytotoxicity of doxorubicinloaded graphene oxides towards Raji B-cells. However, no studies have been reported on the nano-graphene oxide for photodynamic therapy. In this study, we explored the possibility of nano-graphene oxides for photodynamic therapy. Nanoscaled graphene oxide (NGO) was prepared by a modified Hummers’ method. Modification of the NGO was achieved by PEG conjugation for a highly water-soluble NGO-PEG. ZnPc-loaded NGOPEG for in vitro photodynamic therapy towards MCF-7 carcinoma cell line was evaluated.
DONG HaiQing1, ZHAO ZhiLei1, WEN HuiYun1, LI YongYong1*, GUO FangFang, SHEN AiJun1, Pilger FRANK1, LIN Chao1 & SHI DongLu1,2*