NILOP Nanomedicine Research Laboratories, National Institute of Lasers and Optronics College, PIEAS, Islamabad 44000, Pakistan; Department of Pharmacy, University of Peshawar, Peshawar 25000, Pakistan.
NILOP Nanomedicine Research Laboratories, National Institute of Lasers and Optronics College, PIEAS, Islamabad 44000, Pakistan.
J Pharm Sci. 2021 Apr;110(4):1749-1760. doi: 10.1016/j.xphs.2021.01.012. Epub 2021 Jan 16.
Cisplatin therapy faces low bioavailability and clastogenic potential limitations. Early payload leakage of nanocarriers may impair adequate therapeutic efficacy. We propose encapsulation of cisplatin in such nanocarrier that can be externally stimulated for high payload release and enhanced toxicity at site of action. Cisplatin conjugated gold nanorods (Pt-AuNRs) have been synthesized and characterized through UV visible spectroscopy, dynamic light scattering and transmission electron microscopy. Physico-chemical characterization through X-ray photon spectrometry confirms the covalent linkage between linker and aquated cisplatin with AuNRs. Laser exposure (850 nm, CW) enabled ~15-fold payload release from Pt-AuNRs nano-assembly, which is quite high (P < 0.0001) compared to non-stimulated conditions. The median growth inhibitory concentration (GI) after laser exposure of Pt-AuNRs was ~11- and 13-fold low compared to corresponding Pt-AuNRs without laser exposure and cisplatin respectively, in sarcoma cells. Synergistic therapeutic difference is more significant (P < 0.01), at lower concentrations of Pt-AuNRs (0.5-10 μg/mL). Pt-AuNRs photothermal therapy indicates a convincible association of over-production of reactive oxygen species (P < 0.0001) and synergistic therapeutic efficacy. Clastogenic potential is found non-significant for Pt-AuNRs (10 μg/mL). Cisplatin nanoconjugate shows biocompatibility against blood cells. In conclusion, laser-stimulated Pt-AuNRs appear a promising drug delivery with synergistic toxic potential against cancer while attenuating cisplatin toxicity.
顺铂治疗面临生物利用度低和致裂潜能限制。纳米载体的早期有效负载泄漏可能会损害足够的治疗效果。我们建议将顺铂封装在纳米载体中,该载体可以通过外部刺激实现高有效负载释放,并在作用部位增强毒性。已经通过紫外可见光谱法、动态光散射和透射电子显微镜合成和表征了顺铂共轭金纳米棒(Pt-AuNRs)。通过 X 射线光电子能谱法进行的物理化学特性分析证实了连接子与带水剂顺铂与 AuNRs 之间的共价键合。激光照射(850nm,CW)使 Pt-AuNRs 纳米组装体的有效负载释放增加了约 15 倍,与未受刺激的条件相比,这一释放水平相当高(P<0.0001)。激光照射后 Pt-AuNRs 的中值生长抑制浓度(GI)比相应的未经激光照射的 Pt-AuNRs 和顺铂分别低约 11 倍和 13 倍,在肉瘤细胞中。在较低浓度的 Pt-AuNRs(0.5-10μg/mL)下,协同治疗差异更为显著(P<0.01)。Pt-AuNRs 光热疗法表明活性氧(ROS)过度产生(P<0.0001)与协同治疗效果之间存在可靠关联。对于 Pt-AuNRs(10μg/mL),致裂潜能不显著。顺铂纳米缀合物对血细胞表现出良好的生物相容性。总之,激光刺激的 Pt-AuNRs 似乎是一种很有前途的药物输送系统,具有协同的抗癌毒性潜力,同时减轻顺铂的毒性。