Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital - Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Health Technology, Section for Biotherapeutic Engineering and Drug Targeting, Technical University of Denmark, Kongens Lyngby, Denmark.
Int J Nanomedicine. 2023 Feb 17;18:829-841. doi: 10.2147/IJN.S389260. eCollection 2023.
Traditional cancer treatments, such as chemotherapy, are often incapable of achieving complete responses as standalone therapies. Hence, current treatment strategies typically rely on a combination of several approaches. Nanoparticle-based photothermal therapy (PTT) is a technique used to kill cancer cells through localized, severe hyperthermia that has shown promise as an add-on treatment to multiple cancer therapies. Here, we evaluated whether the combination of gold nanoshell (NS)-based PTT and liposomal doxorubicin could improve outcome in a mouse model of colorectal cancer.
First, NS-based PTT was performed on tumor-bearing mice. Radiolabeled liposomes were then injected at different timepoints to follow their accumulation in the tumor and determine the ideal injection time after PTT. In addition, fluorescent liposomes were used to observe the liposomal distribution in the tumor after PTT. Finally, we combined PTT and doxorubicin-loaded liposomes and studied the effect of the treatment strategy on the mice by following tumor growth and survival.
PTT significantly improved liposomal accumulation in the tumor, but only when the liposomes were injected immediately after the therapy. The liposomes accumulated mostly in regions adjacent to the ablated areas. When PTT was combined with liposomal doxorubicin, the mice experienced a slowdown in tumor growth and an improvement in survival.
According to our preclinical study, NS-based PTT seems promising as an add-on treatment for liposomal chemotherapy and potentially other systemic therapies, and could be relevant for future application in a clinical setting.
传统的癌症治疗方法,如化疗,往往无法作为单一疗法实现完全缓解。因此,目前的治疗策略通常依赖于几种方法的联合应用。基于纳米颗粒的光热疗法(PTT)是一种通过局部、严重的高热来杀死癌细胞的技术,作为多种癌症疗法的辅助治疗方法显示出了潜力。在这里,我们评估了金纳米壳(NS)基 PTT 联合脂质体多柔比星是否能改善结直肠癌小鼠模型的治疗效果。
首先,对荷瘤小鼠进行 NS 基 PTT。然后在不同时间点注射放射性标记的脂质体,以观察其在肿瘤中的积累情况,并确定 PTT 后的理想注射时间。此外,还使用荧光脂质体观察 PTT 后脂质体在肿瘤中的分布。最后,我们将 PTT 和载多柔比星的脂质体联合应用,并通过观察肿瘤生长和存活情况来研究该治疗策略对小鼠的影响。
PTT 显著提高了脂质体在肿瘤中的积累,但只有在治疗后立即注射脂质体时才会如此。脂质体主要积聚在消融区域附近。当 PTT 与载多柔比星的脂质体联合应用时,小鼠的肿瘤生长速度减缓,生存时间延长。
根据我们的临床前研究,NS 基 PTT 似乎有望作为脂质体化疗和潜在的其他全身治疗方法的辅助治疗手段,并且可能与未来在临床环境中的应用相关。