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

题目：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领域显示出巨大的应用潜力，如基于碳纳米管（CNT）的靶向给药系统（DDS）用于癌症化疗。典型的碳纳米管靶向DDS系统由增强碳纳米管系统溶解度和生物相容性的功能基团、具有策略设计的调节药物在细胞外装载和在肿瘤细胞内释放的抗癌药物模块和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，并在碳纳米管的功能化、抗癌药物的装载和释放、DDS的细胞内化以及DDS功能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，碳纳米管DDS偶联物中的这种弱相互作用还远远没有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，深入了解抗癌药物与DDS中功能化swcnts之间的非共价相互作用。这些知识最终可以帮助设计基于碳纳米管的新一代药物输送系统。研究目标是：1)通过多尺度分子模型和模拟，深入了解几种有效的典型抗癌药物（阿霉素和紫杉醇）基于碳纳米管的DDS的非共价相互作用，特别是碳纳米管的各种功能化对药物加载/释放机制的影响，以及它们对碳纳米管的pH、长度、直径和手性的依赖，以及碳纳米管的功能化程度和类型。最后，开发一个从头推导的指导方针，以规范基于碳纳米管的DDS的设计。2)通过分析上述广泛的多尺度理论研究，阐明基于碳纳米管的DDS设计的几个重要问题，如导致DOX和PTX不同负载机制的驱动力，负载药物所需和充分的碳纳米管的最佳功能化程度，以及有利的负载药物机制（f-SWCNT侧壁吸附反对封装）。3)研究了抗癌药物在亲水碳簇（HCC）和缺陷石墨烯等新型碳纳米材料上的吸附。该结果可用于验证功能化N/O/ b掺杂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.