Kulkarni Vaishnavi M, Bodas Dhananjay, Dhoble Deepa, Ghormade Vandana, Paknikar Kishore
Nanobioscience, Agharkar Research Institute, G.G. Agarkar Road, Pune 411004, India.
Polymer Science and Engineering Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India.
Colloids Surf B Biointerfaces. 2016 Sep 1;145:878-890. doi: 10.1016/j.colsurfb.2016.06.010. Epub 2016 Jun 10.
Radio-frequency responsive nanomaterials combined with drugs for simultaneous hyperthermia and drug delivery are potential anti-cancer agents. In this study, chitosan coated La0.7Sr0.3MnO3 nanoparticles (C-LSMO NPs) were synthesized and characterized by X-ray diffraction, dynamic light scattering, Fourier transform infra red spectroscopy, vibrating sample magnetometer, scanning electron and atomic force microscopy. Under low radio-frequency (365kHz, RF), C-LSMO NPs (90nm) showed good colloidal stability (+22mV), superparamagnetic nature (15.4 emu/g) and heating capacity (57.4W/g SAR value). Chitosan facilitated doxorubicin entrapment (76%) resulted in DC-LSMO NPs that showed drug release upon a 5min RF exposure. MCF-7 and MDA-MB-231 cancer cells responded to a 5min RF exposure in the presence of bimodal DC-LSMO NPs with a significant decrease in viability to 73% and 88% (Pearson correlation, r=1, P<0.01) respectively, as compared to hyperthermia alone. Internalization of DC-LSMO NPs via the endosomal pathway led to an efficient localization of doxorubicin within the cell nucleus. The ensuing DNA damage, heat shock protein induction, and caspase production triggered apoptotic cell death. Moreover, DC-LSMO NPs successfully restricted the migration of metastatic MDA-MB-231 cancer cells. These data suggest that DC-LSMO NPs are potential bimodal therapeutic agents for cancer treatment and hold promise against disease recurrence and drug resistance.
结合药物用于同时进行热疗和药物递送的射频响应纳米材料是潜在的抗癌剂。在本研究中,合成了壳聚糖包覆的La0.7Sr0.3MnO3纳米颗粒(C-LSMO NPs),并通过X射线衍射、动态光散射、傅里叶变换红外光谱、振动样品磁强计、扫描电子显微镜和原子力显微镜对其进行了表征。在低射频(365kHz,RF)下,C-LSMO NPs(90nm)表现出良好的胶体稳定性(+22mV)、超顺磁性(15.4 emu/g)和加热能力(57.4W/g SAR值)。壳聚糖促进了阿霉素的包封(76%),得到了DC-LSMO NPs,其在5分钟的射频暴露后显示出药物释放。与单独热疗相比,在双峰DC-LSMO NPs存在的情况下,MCF-7和MDA-MB-231癌细胞对5分钟的射频暴露有反应,存活率分别显著降低至73%和88%(Pearson相关性,r = 1,P < 0.01)。DC-LSMO NPs通过内体途径内化导致阿霉素在细胞核内有效定位。随之而来的DNA损伤、热休克蛋白诱导和半胱天冬酶产生引发了凋亡性细胞死亡。此外,DC-LSMO NPs成功地限制了转移性MDA-MB-231癌细胞的迁移。这些数据表明,DC-LSMO NPs是用于癌症治疗的潜在双峰治疗剂,有望对抗疾病复发和耐药性。
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