Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University , Hangzhou 310028, China.
Acc Chem Res. 2014 Jul 15;47(7):2017-25. doi: 10.1021/ar500055s. Epub 2014 May 29.
Efficient assembly in host-guest interactions is crucial to supramolecular nanotechnology. Cyclodextrins (CDs), which possess a hydrophilic exterior surface and hydrophobic interior cavity on the truncated cone, improve the biocompatibility of nanodelivery systems, and hence, supramolecular approaches utilizing CDs can improve and expand the design and applications of functional delivery systems. Owing to good inclusion ability, αCD and βCD are commonly used in the design and construction of supramolecular structures. In this Account, we describe the design strategies to adopt CDs in host-guest delivery systems. Modification of CDs with polymers is popular in current research due to the potential benefits rendered by cationic protection and improved capability. While the process has only minor influence on the host characteristics of the CD cavity, the interaction between the CD and the guest moiety imparts new attributes to the nanosystems with guest-decorated functional groups such as adamantyl poly(ethylene glycol) (PEG) for coating protection, hybrid guests for conformational flexibility, and adamantyl prodrugs for drug delivery. Some specific agents form inclusion complexes with the polymerized βCDs directly and core-shell nanoparticles with hydrophobic cores and are usually created to carry insoluble drugs while the hydrophilic shells offer protection. These unique designs provide the means to practically adapt special characteristics for additional functions or co-delivery. In order to be accepted clinically, delivery systems need to possess extra functions such as controlled particle size, biodegradability, controlled release, and targeted delivery to overcome the hurdles in delivery. These features can be added to biomaterials by self-assembly of functional groups facilitated by the host-guest interactions. Size control by hybridization of switchable polymer compartments in supramolecular structures contributes to the biodistribution utility and biodegradability by incorporating the moieties with hydrolyzable connections and enhancing intracellular degradation and clearance. Controlled release by application of responsive structures like molecular gatings eased by the host-guest interaction can be triggered by the tumor microenvironment at extreme pH and temperature or by external stimuli such as light. Along with the binding selectivity and controlled release, the host-guest nanoparticles show enhanced efficacy in delivery especially to tumors. Recent developments in supramolecular co-delivery systems are described in this Account. Nanoparticles can be designed to carry adamantyl prodrugs and therapeutic nucleotides to tumors so that the released drugs and gene expression synergistically inhibit malignant tissue growth. Optimization of nanoparticle delivery systems by multifunctional transitions yields better biocompatibility and controlled response, and such novel designs will expedite in vivo applications. Hence, multifunctional CD-based host-guest supramolecular nanoparticles with co-delivery ability are expected to have many potential clinical applications.
在主客体相互作用中实现高效组装对于超分子纳米技术至关重要。环糊精（CDs）具有截头锥形的亲水性外表面和疏水性内腔，可提高纳米递药系统的生物相容性，因此，利用 CDs 的超分子方法可以改进和扩展功能递药系统的设计和应用。由于良好的包合能力，α-CD 和 β-CD 通常用于超分子结构的设计和构建。在本综述中，我们描述了在主体-客体递药系统中采用 CDs 的设计策略。由于阳离子保护和性能提高的潜在益处，CD 与聚合物的修饰在当前研究中很受欢迎。虽然该过程对 CD 空腔的主体特征仅有微小影响，但 CD 与客体部分之间的相互作用赋予了纳米系统新的属性，带有金刚烷基聚乙二醇（PEG）等官能团的客体用于涂层保护、构象灵活性的混合客体以及用于药物递释的金刚烷基前药。一些特定的试剂与聚合的β-CD 直接形成包合物，形成具有疏水性核的核壳纳米颗粒，通常用于携带不溶性药物，而亲水性外壳提供保护。这些独特的设计提供了实际适应特殊特性以实现附加功能或共递释的手段。为了在临床上被接受，递药系统需要具有额外的功能，如控制粒径、生物降解性、控制释放和靶向递释，以克服递释中的障碍。这些功能可以通过主体-客体相互作用促进的官能团自组装添加到生物材料中。通过在超分子结构中杂交可切换聚合物隔室来控制粒径有助于生物分布利用和生物降解性，方法是将具有可水解连接的部分并入其中，并增强细胞内降解和清除。通过应用主体-客体相互作用缓解的响应性结构（如分子门控）进行控制释放可以由肿瘤微环境在极端 pH 值和温度下或由外部刺激（如光）触发。与结合选择性和控制释放一起，主体-客体纳米颗粒在递释中显示出增强的功效，特别是在肿瘤部位。本综述描述了最近在超分子共递释系统方面的进展。可以设计纳米颗粒以将金刚烷基前药和治疗性核苷酸递送至肿瘤，使得释放的药物和基因表达协同抑制恶性组织生长。通过多功能转变优化纳米颗粒递释系统可提高生物相容性和控制响应，这种新颖设计将加速体内应用。因此，具有共递释能力的多功能 CD 基主体-客体超分子纳米颗粒有望具有许多潜在的临床应用。
