Understanding Non-covalent Interaction in Carbon Nanotube/Anticancer Drug Conjuga

描述（由申请人提供）：标题：用基于第一性原理的理论方法理解碳纳米管/抗癌药物偶联物中的非共价相互作用碳纳米材料在生物医学应用中显示出巨大的潜力，例如用于癌症化疗的基于碳纳米管（CNT）的靶向药物递送系统（DDS）。典型的CNT靶向DDS系统由增强CNT系统的溶解性和生物相容性的官能团、具有策略性设计的调节药物在细胞外加载和在肿瘤细胞内释放的模块的抗癌药物以及识别肿瘤细胞的肿瘤靶向模块组成。非共价相互作用广泛存在于DDS偶联物中，在碳纳米管的功能化、抗癌药物的负载和释放、DDS的细胞内化以及DDS功能化后碳纳米管的逃逸等各个关键步骤中发挥着重要作用。然而，CNT DDS缀合物中的这种弱相互作用远未在分子水平上得到很好的理解。因此，该项目的主要目标是通过最先进的理论工具，如量子力学（QM），经典分子动力学（MD）和QM/MM，深入了解抗癌药物和DDS中功能化单壁碳纳米管之间的非共价相互作用。这些知识最终可以帮助设计新一代基于碳纳米管的药物递送系统。研究目标是：1）通过多尺度分子模拟，深入研究了碳纳米管DDS与几种典型抗癌药物（阿霉素和紫杉醇）的非共价相互作用，包括碳纳米管的不同功能化对药物载药/释放机制的影响，以及pH、碳纳米管长度、直径和手性对碳纳米管功能化程度和类型的影响。最后，制定一个从头推导的指导方针，规范设计的CNT为基础的DDS。2)通过分析上述广泛的多尺度理论研究，阐明了CNT基DDS设计中的几个重要问题，例如导致DOX和PTX不同载药机制的驱动力，载药所必需和充分的CNT的最佳官能化程度，以及有利的载药机制（在f-SWCNT侧壁上的吸附对包封）。3)研究几种新型碳纳米材料如亲水性碳团簇（HCC）和缺陷石墨烯对抗癌药物的吸附。这些结果可以用来验证功能化的N/O/B掺杂的石墨烯可能是药物载体的潜在候选者的假设。

DESCRIPTION (provided by applicant): Title: Understanding Non-covalent Interaction in Carbon Nanotube/Anticancer Drug Conjugates with the First-principles Based Theoretical Methods Carbon nanomaterials have shown great potential in biomedical applications, such as carbon nanotube (CNT)-based targeting drug delivery system (DDS) for cancer chemotherapy. A typical CNT targeting DDS system consists of functional groups that enhance solubility and biocompatibility of the CNT system, anticancer drugs with strategically designed module regulating drugs loading extracellularly and releasing inside tumor cells and tumor-targeting module recognizing tumor cells. Non-covalent interactions widely exist in the DDS conjugates, and play very important roles in every essential step, including functionalization of CNTs, loading and releasing of anticancer drugs, cellular internalization of the DDS as well as escaping of the CNT after function of the DDS. However, such weak interactions in the CNT DDS conjugates are far from being well understood at a molecular level. Major goal of the project is therefore to gain a deep understanding of the non-covalent interactions between anticancer drug and functionalized SWCNT in the DDS through state-of-the-art theoretical tools, such as quantum mechanical (QM), classical molecular dynamics (MD), and QM/MM. Such knowledge could eventually help design a new generation of drug delivery systems based on CNTs. The research objectives are: 1) To provide a good understanding about the non-covalent interactions for the CNT- based DDS for a couple of effective typical anticancer drugs (doxorubicin and paclitaxel) via multiscale molecular modeling and simulations, specifically, the effects of various functionalization of CNT on the drug loading/releasing mechanism, their dependences on pH, length, dimeter and chirality of CNT, and degree and type of functionalization of the CNTs. Eventually, develop an ab initio derived guideline for regulating the design of CNT-based DDS. 2) To clarify a few important issues for the design of the CNT-based DDS by analyzing the above extensive multiscale theoretical investigation, such as driving forces that lead to the different loading mechanisms for the DOX and PTX, the optimum degree of functionalization of CNT that is necessary and sufficient for drug loading, and the favorable drug loading mechanism (adsorption on sidewall of f-SWCNT against encapsulation). 3) To investigate the adsorptions of the anticancer drugs on a few novel carbon nanomaterials such as hydrophilic carbon clusters (HCC), and defective graphenes. The results can be used to test the hypothesis that the functionalized N/O/B-doped graphenes may be potential candidates for drug carrier.