Rahimi Maham, Kilaru Sunitha, Sleiman Ghida El Hajj, Saleh Anas, Rudkevich Dmitry, Nguyen Kytai
Biomedical Engineering Program, University of Texas Southwestern Medical Center at Dallas and University of Texas at Arlington.
J Biomed Nanotechnol. 2008 Dec 1;4(4):482-490. doi: 10.1166/jbn.2008.014.
The aim of this research project was to develop new temperature sensitive nanoparticles that have a lower critical solution temperature (LCST) that is above body temperature and can be incorporated with various molecules at the surface. The poly(N-isopropylacrylamide-co-acrylamide-co-allylamine) (NIPA-AAm-AH) nanoparticles were synthesized through a free radical polymerization method. NIPA was polymerized with AAm and AH to increase the LCST and to provide amine groups for functionalization, respectively. Using transmission electron microscopy (TEM) and laser scattering technology, the sizes of these nanoparticles were found to be inversely proportional to the surfactant concentrations. In addition, the LCST of the 100-nm NIPA-AAm-AH nanoparticles was approximately 40 degrees C measured by a spectrophotometer. The chemical composition of the NIPA-AAm-AH nanoparticles determined with Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) also confirmed the presence of functional groups of each monomer. The nanoparticles were also successfully conjugated to bovine anti-rabbit IgG-Texas Red as a model for future bioconjugation. Furthermore, nanoparticles did not show significant cytotoxicity activity against human fibroblast cells. Finally, doxorubicin (DOX) was used in order to investigate the drug release profiles of the NIPA-AAm-AH nanoparticles at different temperatures. The results indicated that DOX was released more at 41 degrees C compared to that of 37 degrees C and 4 degrees C, which is evidence for temperature sensitivity of the nanoparticles. Future work will investigate the pharmacological and targeted capabilities of the synthesized nanoparticles conjugated to antibodies for possible application in controlled and targeted drug delivery.
本研究项目的目的是开发新型温度敏感纳米颗粒，其具有高于体温的较低临界溶液温度（LCST），并且可以在表面结合各种分子。通过自由基聚合法合成了聚（N-异丙基丙烯酰胺-共-丙烯酰胺-共-烯丙胺）（NIPA-AAm-AH）纳米颗粒。NIPA分别与AAm和AH聚合，以提高LCST并提供用于功能化的胺基。使用透射电子显微镜（TEM）和激光散射技术，发现这些纳米颗粒的尺寸与表面活性剂浓度成反比。此外，通过分光光度计测量，100nm的NIPA-AAm-AH纳米颗粒的LCST约为40℃。用傅里叶变换红外光谱（FTIR）和核磁共振（NMR）测定的NIPA-AAm-AH纳米颗粒的化学成分也证实了每种单体官能团的存在。纳米颗粒还成功地与牛抗兔IgG-德克萨斯红偶联，作为未来生物偶联的模型。此外，纳米颗粒对人成纤维细胞没有显示出明显的细胞毒性活性。最后，使用阿霉素（DOX）来研究NIPA-AAm-AH纳米颗粒在不同温度下的药物释放曲线。结果表明，与37℃和4℃相比，DOX在41℃时释放更多，这是纳米颗粒温度敏感性的证据。未来的工作将研究与抗体偶联的合成纳米颗粒的药理和靶向能力，以便在可控和靶向药物递送中可能应用。
