Armanetti Paolo, Chillà Anastasia, Margheri Francesca, Biagioni Alessio, Menichetti Luca, Margheri Giancarlo, Ratto Fulvio, Centi Sonia, Bianchini Francesca, Severi Mirko, Traversi Rita, Bani Daniele, Lulli Matteo, Del Rosso Tommaso, Mocali Alessandra, Rovida Elisabetta, Del Rosso Mario, Fibbi Gabriella, Laurenzana Anna
Institute of Clinical Physiology (IFC) National Research Council Pisa 56124 Italy.
Department of Experimental and Clinical Biomedical Sciences University of Florence Florence 50134 Italy.
Adv Sci (Weinh). 2020 Dec 21;8(4):2001175. doi: 10.1002/advs.202001175. eCollection 2021 Feb.
Near infrared (NIR)-resonant gold nanoparticles (AuNPs) hold great promise in cancer diagnostics and treatment. However, translating the theranostic potential of AuNPs into clinical applications still remains a challenge due to the difficulty to improve the efficiency and specificity of tumor delivery in vivo as well as the clearance from liver and spleen to avoid off target toxicity. In this study, endothelial colony forming cells (ECFCs) are exploited as vehicles to deliver AuNPs to tumors. It is first demonstrated that ECFCs display a great capability to intake AuNPs without losing viability, and exert antitumor activity per se. Using a human melanoma xenograft mouse model, it is next demonstrated that AuNP-loaded ECFCs retain their capacity to migrate to tumor sites in vivo 1 day after injection and stay in the tumor mass for more than 1 week. In addition, it is demonstrated that ECFC-loaded AuNPs are efficiently cleared by the liver over time and do not elicit any sign of damage to healthy tissue.
近红外(NIR)共振金纳米颗粒(AuNP)在癌症诊断和治疗方面具有巨大潜力。然而,由于难以提高体内肿瘤递送的效率和特异性以及从肝脏和脾脏清除以避免脱靶毒性,将AuNP的诊疗潜力转化为临床应用仍然是一项挑战。在本研究中,内皮祖细胞(ECFC)被用作将AuNP递送至肿瘤的载体。首先证明,ECFC具有摄取AuNP的强大能力且不丧失活力,并且本身具有抗肿瘤活性。使用人黑色素瘤异种移植小鼠模型,接下来证明,负载AuNP的ECFC在注射后1天仍保留其在体内迁移至肿瘤部位的能力,并在肿瘤块中停留超过1周。此外,证明随着时间的推移,负载ECFC的AuNP被肝脏有效清除,并且不会引发对健康组织的任何损伤迹象。