新穎單分子鏈微胞:結構設計及功能性應用

Abstract

最近我們已經能成功的製備一種新穎的水溶性奈米粒子，通過共價和非共價相互作用，模仿天然蛋白質的折疊，產生新的“單鏈高分子納米粒子”（SCPNs）其具有獨特的結構和優異性能。在本研究中，透過活性聚合的方式將已官能基化的甲基丙烯酸(寡（乙二醇）)酯單體摻入能自組裝鍵結的多點式氫鍵組共聚物。這種材料是透過多點式氫鍵相互作用自組裝成物理交聯的聚合物網絡，由親水性的聚乙二醇（PEG）鏈段作為外殼可以自組裝在水溶液中形成球形SCPNs。所製備的SCPNs從應用的角度來看是非常有吸引力的，因為它們具有非常低的臨界微胞濃度（<10-4 g/L）和均勻的直徑(約25nm)，這使得它們非常穩定和顯著降低比黏度。另外，在不同溫度和濃度測試中，能維持均一且穩定的粒徑，而且在介面活性劑的存在下SCPNs和載藥的SCPNs也都能維持動力學穩定。此外，我們還觀察到，在包覆葉酸後會影響SCNPs微胞在水溶液中的形成且與以往的結果相比，有顯著高藥物附載率（19.6％）。在高於最低臨界溫度時，pH值敏感的氫鍵網絡允許在溫和的酸性條件下（pH = 4）的促進釋放附載的藥物，在24 h後可達66.7％的釋放。由以上結果，我們所開發的新一代SCNPs具有很大的潛力可以作為下一代以超分子聚合物設計成的功能性奈米材料。

Recent innovation in water-based polymeric nanoparticle has shown significant promise to mimic the folding of natural proteins by generating novel “single-chain polymeric nanoparticles” (SCPNs) through covalent and non-covalent interactions, which have gained prominence in nanotechnology and nanomedicine due to their unique structures and exceptional properties. In this study, a practical approach to the living polymerization of functionalized oligo(ethylene glycol) methacrylate monomer allows for incorporation of self-constituted multiple hydrogen bonded groups into homopolymer. This material is able to self-assemble through multiple hydrogen bonding interactions into physically core-crosslinked polymeric networks, which by hydrophilic poly(ethylene glycol) segments as the outer shell can self-assemble in aqueous solutions to form spherical SCPNs. The resulting SCPNs are very attractive from a practical point of view, since they have a very low critical micellization concentration (< 10-4 g/L) with an almost uniform diameter of about 25 nm, which makes them extremely stable with a significant reduction in the specific viscosity. In addition, the mean value of the particle size is not only significantly stabled by variables such as temperature and concentration, but also improved kinetic stability of SCPNs and drug-loaded SCPNs in the presence of a destabilizing agent. Moreover, we also observed that the incorporation of anticancer drug affected the micellization process of SCPNs in aqueous solution and enabled significantly higher loading of the drug (19.6 %), compared with previous results. Above the lower critical solution temperature, the pH-sensitive hydrogen bonded network allows the facilitated release of entrapped drug under mildly acidic conditions (pH= 4), with a release of up to 66.7 % of bound drug in 24 h. Thus, these results suggest that this newly developed SCPN is a potential architecture in future supramolecular polymer designs for next-generation functional nano-materials.