Drug delivery platforms are anticipated to have biocompatible and bioinert surfaces. PEGylation of drug carriers is the most approved method since it improves water solubility and colloid stability and decreases the drug vehicles’ interactions with blood components. Although this approach extends their biocompatibility, biorecognition mechanisms prevent them from biodistribution and thus efficient drug transfer. Recent studies have shown (poly)zwitterions to be alternatives for PEG with superior biocompatibility. (Poly)zwitterions are super hydrophilic, mainly stimuli-responsive, easy to functionalize and they display an extremely low protein adsorption and long biodistribution time. These unique characteristics make them already promising candidates as drug delivery carriers. Furthermore, since they have highly dense charged groups with opposite signs, (poly)zwitterions are intensely hydrated under physiological conditions. This exceptional hydration potential makes them ideal for the design of therapeutic vehicles with antifouling capability, i.e., preventing undesired sorption of biologics from the human body in the drug delivery vehicle. Therefore, (poly)zwitterionic materials have been broadly applied in stimuli-responsive “intelligent” drug delivery systems as well as tumor-targeting carriers because of their excellent biocompatibility, low cytotoxicity, insignificant immunogenicity, high stability, and long circulation time. To tailor (poly)zwitterionic drug vehicles, an interpretation of the structural and stimuli-responsive behavior of this type of polymer is essential. To this end, a direct study of molecular-level interactions, orientations, configurations, and physicochemical properties of (poly)zwitterions is required, which can be achieved via molecular modeling, which has become an influential tool for discovering new materials and understanding diverse material phenomena. As the essential bridge between science and engineering, molecular simulations enable the fundamental understanding of the encapsulation and release behavior of intelligent drug-loaded (poly)zwitterion nanoparticles and can help us to systematically design their next generations. When combined with experiments, modeling can make quantitative predictions. This perspective article aims to illustrate key recent developments in (poly)zwitterion-based drug delivery systems. We summarize how to use predictive multiscale molecular modeling techniques to successfully boost the development of intelligent multifunctional (poly)zwitterions-based systems.

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基于多两性离子的药物输送平台建模：对当前最先进技术及未来的展望

预计药物输送平台将具有生物相容性和生物惰性表面。药物载体的聚乙二醇化是最被认可的方法，因为它提高了水溶性和胶体稳定性，并减少了药物载体与血液成分的相互作用。尽管这种方法扩展了它们的生物相容性，但生物识别机制阻止了它们的生物分布和有效的药物转移。最近的研究表明，（多）两性离子是具有优异生物相容性的 PEG 的替代品。(聚)两性离子具有超亲水性，主要对刺激有响应性，易于功能化，并且具有极低的蛋白质吸附和较长的生物分布时间。这些独特的特性使它们已经成为药物输送载体的有希望的候选者。此外，由于它们具有高度密集的带相反符号的带电基团，因此（多）两性离子在生理条件下会强烈水合。这种卓越的水合潜力使它们成为设计具有防污能力的治疗载体的理想选择，IE.，防止生物制剂在药物输送载体中从人体中发生不希望的吸附。因此，（多）两性离子材料具有良好的生物相容性、低细胞毒性、免疫原性低、稳定性高、循环时间长等优点，已被广泛应用于刺激响应的“智能”药物递送系统和肿瘤靶向载体。为了定制（多）两性离子药物载体，解释这种聚合物的结构和刺激响应行为是必不可少的。为此，需要对（多）两性离子的分子水平相互作用、取向、构型和物理化学性质进行直接研究，这可以通过分子建模来实现，这已成为发现新材料和理解多种材料的重要工具现象。作为科学与工程之间的重要桥梁，分子模拟能够从根本上理解智能载药（多）两性离子纳米粒子的封装和释放行为，并可以帮助我们系统地设计它们的下一代。当与实验相结合时，建模可以做出定量预测。这篇观点文章旨在说明基于（多）两性离子的药物输送系统的主要近期发展。我们总结了如何使用预测性多尺度分子建模技术成功地促进智能多功能（多）两性离子系统的开发。分子模拟能够从根本上理解智能载药（多）两性离子纳米粒子的封装和释放行为，并可以帮助我们系统地设计它们的下一代。当与实验相结合时，建模可以做出定量预测。这篇观点文章旨在说明基于（多）两性离子的药物输送系统的主要近期发展。我们总结了如何使用预测性多尺度分子建模技术成功地促进智能多功能（多）两性离子系统的开发。分子模拟能够从根本上理解智能载药（多）两性离子纳米粒子的封装和释放行为，并可以帮助我们系统地设计它们的下一代。当与实验相结合时，建模可以做出定量预测。这篇观点文章旨在说明基于（多）两性离子的药物输送系统的主要近期发展。我们总结了如何使用预测性多尺度分子建模技术成功地促进智能多功能（多）两性离子系统的开发。