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Stimuli responsive self fluorescent nanogels for colon cancer theranostic applications

机译:刺激响应自发荧光纳米凝胶在结肠癌治疗中的应用

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Introduction: Theranostics is an emerging area in nanomedicine which combines both therapy and diagnostics in a single domain. Polymer based theranostic agents are of particular interest as they are characterized by great diversity in terms of diagnostic and imaging modalities. The current strategy of constructing a polymer-based theranostic agent relies on the incorporation of fluorophores and magnetic resonance imaging contrast agents which have inherent drawbacks such as toxicity, high cost, low sensitivity and non-biodegradability. Hence development of low cost and biocompatible PEG based self fluorescent polymeric theranostic systems is of great importance in biomedical research. Methods: A fluorescent PEGylated comacromer was synthesized by polycondensation of PEG with maleic acid and glycine. The structure and photoluminescence of the to from nanogel. 5-Fluorouracil, a model colon cancer drug, was loaded inside the nanogel and studied the drug release. The colon cancer imaging capability of this nanogel was evaluated with HCT cell line. Results and Discussion: The PEGylated comacromer is comprised of the units of maleic acid, PEG and glycine as revealed by the proton NMR spectra (Figure 1 a) with peaks at 6.8 ppm (CH=CH of maleic acid), 3.6 ppm (-CH2 groups of PEG) and 3.4 ppm (-CH2NH from glycine). The studies on fluorescence characteristics of the PEGylated comacromer reveal excitation dependent fluorescence characteristics (Fig 1 b) Figure 1: proton NMR spectra of PEGylated comacromer (a), Fluorescent spectra of PEGylated comacromer (b) The size of synthesized nanogels was around 100 nm (Fig 2a). The studies on drug release of nanogel reveal pH sensitive drug release profile (Fig2b). The nanogel can cross the acidic pH of intestine and deliver more amount of drug in the colon having slightly alkaline pH. The observed higher drug release in alkaline pH is attributed to the ionizable -COOH groups of methacrylic acid which causes swelling in basic pH The studies on colon cancer imaging capability of this nanogel exhibit multiple emissions from colon cancer cell line (Fig 2c). Figure 2: Transmission electron microscopy images of nanogels (a),pH sensitive drug release profile of 5-fluorouracil from nanogels (b), Colon cancer cell line (HCT) fluorescent imaging using nanogels (c) Conclusion: The present nanogel of PEGylated comacromer displayed favorable therapeutic and diagnostic (theranostic) capabilities for colon cancer. To best of our knowledge this is the first report of a PEG based self fluorescent nanogel for colon cancer theranostic applications.
机译:简介:Theranostics是纳米医学中的一个新兴领域,在单个领域将治疗和诊断结合在一起。基于聚合物的治疗剂特别受关注,因为它们的诊断和成像方式具有极大的多样性。构造基于聚合物的治疗剂的当前策略依赖于荧光团和磁共振成像造影剂的结合,所述荧光团和磁共振成像造影剂具有固有的缺点,例如毒性,高成本,低灵敏度和不可生物降解性。因此,开发低成本和基于生物相容性PEG的自发荧光聚合物治疗方法体系在生物医学研究中具有重要意义。方法:通过PEG与马来酸和甘氨酸的缩聚反应,合成了一种荧光PEG化共聚体。纳米凝胶的结构和光致发光。将5-氟尿嘧啶(一种模型结肠癌药物)加载到纳米凝胶中,并研究了药物释放。用HCT细胞系评估了这种纳米凝胶的结肠癌成像能力。结果与讨论:质子NMR谱图(图1a)显示,聚乙二醇化的共聚体由马来酸,聚乙二醇和甘氨酸组成,其峰分别在6.8 ppm(CH = CH顺丁烯二酸),3.6 ppm(-CH2)处。 PEG)和3.4 ppm(来自甘氨酸的-CH2NH)。聚乙二醇化共聚体的荧光特性研究揭示了激发相关的荧光特性(图1b)图1:聚乙二醇化共聚体的质子NMR光谱(a),聚乙二醇化共聚体的荧光光谱(b)合成纳米凝胶的大小约为100 nm(图2a)。纳米凝胶药物释放的研究揭示了pH敏感的药物释放曲线(图2b)。纳米凝胶可以穿过肠道的酸性pH,并在具有弱碱性pH的结肠中递送更多量的药物。在碱性pH值下观察到的更高的药物释放归因于甲基丙烯酸的可电离的-COOH基团,该基团导致碱性pH值膨胀。这种纳米凝胶对结肠癌成像能力的研究显示出结肠癌细胞系产生了多种排放物(图2c)。图2:纳米凝胶的透射电子显微镜图像(a),5-氟尿嘧啶从纳米凝胶的pH敏感药物释放曲线(b),使用纳米凝胶的结肠癌细胞系(HCT)荧光成像(c)结论:聚乙二醇化共聚体的纳米凝胶对结肠癌显示出良好的治疗和诊断(热疗)能力。据我们所知,这是基于PEG的自发荧光纳米凝胶在结肠癌治疗应用中的首次报道。

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