Biocompatible, colloidally stable and ultra-small Fe₃O₄ nanoparticles (SPIONs) coated with poly(N-isopropylacrylamide) (PNIPAM) were synthesized via surface-initiated ATRP (atom transfer radical polymerization) to prevent excessive aggregation of magnetic cores and interparticle crosslinking, and to provide control over polymer content. These SPION-PNIPAM nanoparticles (NPs) have a hydrodynamic size between 8 and 60 nm depending on the PNIPAM content, and hence are ultrasmall in size and have an LCST around 38 °C. They had a high drug-loading capacity reaching 9.6 wt% doxorubicin in the final composition. The Dox release studies revealed pH and temperature-dependent release, which was not reported for PNIPAM before. Release of Dox under physiological conditions was below 20%, but around 90% at 42 °C and pH 5. This dually responsive nature is very advantageous to increase the drug efficacy and reduce side-effects, simultaneously. The cytocompatability of the SPION-PNIPAM NPs and the influence of Dox delivery to cells were investigated via in vitro cell viability, apoptosis, DNA-damage and confocal microscopy studies. The NPs were shown to be highly cytocompatible and induce significant cell death due to Dox when loaded with the drug. Besides, it was seen that the polymeric content can be used as an additional factor in tuning the release kinetics. Lastly, these nanoparticles reduced the signal intensity significantly in the T2 mode, acting as a potential SPION-based contrast agent. Overall, here, we demonstrate the design of small, smart theranostic nanoparticles with high drug-loading capacity and pH-dependent temperature-sensitive release characteristics with the ability to generate contrast in MRI.

中文翻译：

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通过ATRP开发量身定制的SPION-PNIPAM纳米颗粒，用于双重响应的阿霉素递送和MR成像†

生物相容性，胶体稳定和超小Fe ₃ O ₄纳米粒子（SPIONs）包覆有聚N-异丙基丙烯酰胺（PNIPAM）。表面引发的ATRP（原子转移自由基聚合）可防止磁芯过度聚集和粒子间交联，并提供对聚合物含量的控制。这些SPION-PNIPAM纳米颗粒（NPs）的流体力学尺寸取决于PNIPAM含量，介于8到60 nm之间，因此尺寸非常小，LCST约为38°C。它们具有高的载药量，在最终组合物中达到了9.6 wt％的阿霉素。Dox释放研究揭示了pH和温度依赖性释放，这在PNIPAM之前没有报道。在生理条件下，Dox的释放低于20％，但在42°C和pH 5时释放约90％。这种双重响应性质对于同时提高药物疗效和减少副作用非常有利。通过体外细胞活力，细胞凋亡，DNA损伤和共聚焦显微镜研究。NPs表现出高度的细胞相容性，并且在装载药物后会因Dox诱导明显的细胞死亡。此外，可以看出，聚合物含量可以用作调节释放动力学的附加因素。最后，这些纳米粒子在T2模式下显着降低了信号强度，用作潜在的基于SPION的造影剂。总体而言，在这里，我们展示了具有高载药量和pH依赖的温度敏感释放特性以及能够在MRI中产生对比的智能小巧的治疗治疗纳米颗粒的设计。