†Istituto Italiano di Tecnologia, via Morego 30, 16143, Genova, Italy.
‡King Abdullah University of Science and Technology (KAUST), BESE division, Thuwal, Kingdom of Saudi Arabia.
ACS Appl Mater Interfaces. 2015 May 20;7(19):10132-45. doi: 10.1021/am5088117. Epub 2015 May 5.
Herein, we prepare nanohybrids by incorporating iron oxide nanocubes (cubic-IONPs) within a thermoresponsive polymer shell that can act as drug carriers for doxorubicin(doxo). The cubic-shaped nanoparticles employed are at the interface between superparamagnetic and ferromagnetic behavior and have an exceptionally high specific absorption rate (SAR), but their functionalization is extremely challenging compared to bare superparamagnetic iron oxide nanoparticles as they strongly interact with each other. By conducting the polymer grafting reaction using reversible addition-fragmentation chain transfer (RAFT) polymerization in a viscous solvent medium, we have here developed a facile approach to decorate the nanocubes with stimuli-responsive polymers. When the thermoresponsive shell is composed of poly(N-isopropylacrylamide-co-polyethylene glycolmethyl ether acrylate), nanohybrids have a phase transition temperature, the lower critical solution temperature (LCST), above 37 °C in physiological conditions. Doxo loaded nanohybrids exhibited a negligible drug release below 37 °C but showed a consistent release of their cargo on demand by exploiting the capability of the nanocubes to generate heat under an alternating magnetic field (AMF). Moreover, the drug free nanocarrier does not exhibit cytotoxicity even when administered at high concentration of nanocubes (1g/L of iron) and internalized at high extent (260 pg of iron per cell). We have also implemented the synthesis protocol to decorate the surface of nanocubes with poly(vinylpyridine) polymer and thus prepare pH-responsive shell coated nanocubes.
在此，我们通过将氧化铁纳米立方（立方 IONP）纳入热敏聚合物壳中来制备纳米杂化物，该聚合物壳可用作阿霉素（doxo）的药物载体。所使用的立方形状的纳米颗粒处于超顺磁和铁磁行为之间的界面，具有极高的比吸收率（SAR），但与裸露的超顺磁性氧化铁纳米颗粒相比，其功能化极具挑战性，因为它们之间的相互作用非常强烈。通过在粘性溶剂介质中使用可逆加成-断裂链转移（RAFT）聚合进行聚合物接枝反应，我们开发了一种简便的方法来用响应性聚合物修饰纳米立方。当热敏聚合物壳由聚（N-异丙基丙烯酰胺-co-聚乙二醇甲基醚丙烯酸酯）组成时，纳米杂化物在生理条件下具有高于 37°C 的相转变温度，即低临界溶液温度（LCST）。负载阿霉素的纳米杂化物在低于 37°C 时表现出可忽略不计的药物释放，但通过利用纳米立方在交变磁场（AMF）下产生热量的能力，可以按需持续释放其货物。此外，即使在纳米立方的高浓度（1g/L 的铁）下给药并且内化程度高（每个细胞 260pg 的铁）时，无药物的纳米载体也没有表现出细胞毒性。我们还实施了合成方案，通过将聚（4-乙烯吡啶）聚合物修饰纳米立方的表面，从而制备 pH 响应性壳涂层纳米立方。
