Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Department of Basic Pharmaceutical Sciences, Fred Wilson School of Pharmacy, High Point University, High Point, NC, 27268, USA.
Int J Nanomedicine. 2021 Feb 5;16:851-865. doi: 10.2147/IJN.S296513. eCollection 2021.
Ionizing radiation (IR) is commonly used in triple-negative breast cancer (TNBC) treatment regimens. However, off-target toxicity affecting normal tissue and grueling treatment regimens remain major limitations. Hyperthermia is one of the greatest IR sensitizers, but only if heat is administered simultaneously or immediately prior to ionizing radiation. Difficulty in co-localizing ionizing radiation (IR) in rapid succession with hyperthermia, and confining treatment to the tumor have hindered widespread clinical adoption of combined thermoradiation treatment. Metal nanoparticle-based approaches to IR sensitization and photothermal heat generation may aid in overcoming these issues and improve treatment specificity.
We assessed the potential to selectively treat MDA-MB-231 TNBC cells without affecting non-malignant MCF-10A breast cells using a multimodal approach based upon combined photothermal therapy, IR sensitization, and specific cytotoxicity using triangular silver nanoparticles (TAgNPs) with peak absorbance in the near-infrared light (NIR) spectrum.
We found that TAgNP-mediated photothermal therapy and radiosensitization offer a high degree of specificity for treatment of TNBC without affecting non-malignant mammary epithelial cells.
If given at a high enough dose, IR, heat, or TAgNPs alone could be sufficient for tumor treatment. However, when the dose of one or all of these modalities increases, off-target effects also increase. The challenge lies in identifying the minimal doses of each individual treatment such that when combined they provide maximum selectivity for treatment of TNBC cells with minimum off-target effects on non-malignant breast cells. Our results provide proof of concept that this combination is highly selective for TNBC cells while sparing non-malignant mammary epithelial cells. This treatment would be particularly important for patients undergoing breast conservation therapy and for treatment of invasive tumor margins near the periphery where each individual treatment might be at a sub-therapeutic level.
电离辐射（IR）常用于三阴性乳腺癌（TNBC）的治疗方案中。然而，影响正常组织的非靶向毒性和苛刻的治疗方案仍然是主要的限制因素。热疗是最大的电离辐射增敏剂之一，但前提是热量要在电离辐射之前同时或立即给予。由于难以将电离辐射（IR）与热疗快速协同作用，并将治疗局限于肿瘤，因此联合热放疗的广泛临床应用受到阻碍。基于金属纳米颗粒的电离辐射增敏和光热产热方法可能有助于克服这些问题并提高治疗的特异性。
我们评估了使用基于联合光热疗法、电离辐射增敏和使用具有近红外光（NIR）光谱峰值吸收的三角银纳米颗粒（TAgNPs）的特异性细胞毒性的多模态方法，选择性治疗 MDA-MB-231 TNBC 细胞而不影响非恶性 MCF-10A 乳腺细胞的潜力。
我们发现，TAgNP 介导的光热疗法和放射增敏对治疗 TNBC 具有高度的特异性，而不会影响非恶性乳腺上皮细胞。
如果给予足够高的剂量，IR、热或 TAgNPs 本身就足以治疗肿瘤。然而，当这些模式中的一种或多种剂量增加时，非靶向效应也会增加。挑战在于确定每种单独治疗的最小剂量，以便当它们结合使用时，它们可以为 TNBC 细胞的治疗提供最大的选择性，同时对非恶性乳腺细胞的非靶向效应最小。我们的结果提供了一个概念证明，即这种组合对 TNBC 细胞具有高度的选择性，同时对非恶性乳腺上皮细胞具有最小的选择性。对于接受保乳治疗的患者以及治疗外周附近的侵袭性肿瘤边缘的患者，这种治疗尤其重要，因为每种单独的治疗可能处于亚治疗水平。
