Jenkins Samir V, Nedosekin Dmitry A, Shaulis Barry J, Wang Tengjiao, Jamshidi-Parsian Azemat, Pollock Erik D, Chen Jingyi, Dings Ruud P M, Griffin Robert J
Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, AR.
Department of Otolaryngology and Phillips Classic Laser and Nanomedicine Laboratories, University of Arkansas for Medical Sciences, Little Rock, AR.
Nanotheranostics. 2019 Mar 22;3(2):145-155. doi: 10.7150/ntno.32395. eCollection 2019.
A major challenge in photothermal treatment is generating sufficient heat to eradicate diseased tissue while sparing normal tissue. Au nanomaterials have shown promise as a means to achieve highly localized photothermal treatment. Toward that end, the synthetic peptide anginex was conjugated to Au nanocages. Anginex binds to galectin-1, which is highly expressed in dividing endothelial cells found primarily in the tumor vasculature. The skin surface temperature during a 10 min laser exposure of subcutaneous murine breast tumors did not exceed 43°C and no normal tissue damage was observed, yet a significant anti-tumor effect was observed when laser was applied 24 h post-injection of targeted nanocages. Untargeted particles showed little effect in immunocompetent, tumor-bearing mice under these conditions. Photoacoustic, photothermal, and ICP-MS mapping of harvested tissue showed distribution of particles near the vasculature throughout the tumor. This uptake pattern within the tumor combined with a minimal overall temperature rise were nonetheless sufficient to induce marked photothermal efficacy and evidence of tumor control. Importantly, this evidence suggests that bulk tumor temperature during treatment does not correlate with treatment outcome, which implies that targeted nanomedicine can be highly effective when closely bound/distributed in and around the tumor endothelium and extensive amounts of direct tumor cell binding may not be a prerequisite of effective photothermal approaches.
光热治疗中的一个主要挑战是在不损伤正常组织的情况下产生足够的热量来根除病变组织。金纳米材料已显示出有望成为实现高度局部化光热治疗的一种手段。为此，将合成肽血管抑素（anginex）与金纳米笼偶联。血管抑素与半乳糖凝集素-1结合，半乳糖凝集素-1在主要存在于肿瘤脉管系统中的增殖内皮细胞中高度表达。对皮下小鼠乳腺肿瘤进行10分钟激光照射期间，皮肤表面温度不超过43°C，未观察到正常组织损伤，但在注射靶向纳米笼24小时后施加激光时，观察到显著的抗肿瘤效果。在这些条件下，非靶向颗粒在有免疫能力的荷瘤小鼠中几乎没有效果。对收获组织进行的光声、光热和电感耦合等离子体质谱映射显示，颗粒在整个肿瘤的脉管系统附近分布。尽管肿瘤内的这种摄取模式与总体温度的最小升高相结合，但仍足以诱导显著的光热疗效和肿瘤控制证据。重要的是，这一证据表明治疗期间的大块肿瘤温度与治疗结果无关，这意味着当靶向纳米药物紧密结合/分布在肿瘤内皮及其周围时，可能非常有效，大量直接的肿瘤细胞结合可能不是有效光热方法的先决条件。
