Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, Colorado 80303, United States.
Renewable and Sustainable Energy Institute, University of Colorado Boulder, Boulder, Colorado 80303, United States.
ACS Biomater Sci Eng. 2021 May 10;7(5):1863-1875. doi: 10.1021/acsbiomaterials.0c01406. Epub 2021 Jan 12.
Drug-resistant bacterial infections are a growing cause of illness and death globally. Current methods of treatment are not only proving less effective but also perpetuate evolution of new resistance. Here we propose, through an model, a new treatment for drug-resistant bacterial infection that uses semiconductor nanoparticles, called quantum dots (QDs), that can be activated by light to produce superoxide to specifically and effectively kill drug-resistant bacteria. We adapt this technology for assessment of toxicity and treatment of a subcutaneous infection in mice. As our cadmium telluride QDs with 2.4 eV band gap (CdTe-2.4 QDs) are activated by blue light, we engineered LED patches to adhere to the infection site on mice, thus providing the light necessary for the activity of injected QDs and treatment of the infection. We show, through assessment of body weight, histology, and inflammation and oxidative stress markers in serum, that the CdTe-2.4 QDs are nontoxic at concentrations that reduce drug-resistant bacterial viability in subcutaneous abscesses. Further, CdTe-2.4 QDs did not accumulate in the body and were safely excreted in urine via renal clearance. CdTe-2.4 QD treatment decreased abscess viability by as much as 7 orders of magnitude. We thus propose an alternative treatment approach for drug-resistant topical infections: the injection of a low concentration of QDs and the application of an adhesive patch comprising only an LED and a battery. This treatment could revolutionize last-resort treatments of burn wounds, cellulitis, and other skin infections.
耐药细菌感染是全球范围内导致疾病和死亡的一个日益严重的问题。目前的治疗方法不仅效果越来越差,而且还促进了新的耐药性的产生。在这里,我们通过一个模型提出了一种新的治疗耐药细菌感染的方法,该方法使用半导体纳米粒子,称为量子点(QD),可以通过光激活产生超氧化物,从而特异性和有效地杀死耐药细菌。我们将这项技术用于评估毒性和治疗小鼠的皮下感染。由于我们的带隙为 2.4eV 的碲化镉量子点(CdTe-2.4 QDs)可以被蓝光激活,因此我们设计了 LED 贴片来贴合小鼠的感染部位,从而为注入的 QDs 的活性和感染的治疗提供所需的光。通过评估体重、组织学、血清中的炎症和氧化应激标志物,我们表明,在降低皮下脓肿中耐药细菌活力的浓度下,CdTe-2.4 QDs 是无毒的。此外,CdTe-2.4 QDs 不会在体内积累,而是通过肾脏清除以尿液的形式安全排泄。CdTe-2.4 QD 治疗使脓肿的活力降低了多达 7 个数量级。因此,我们提出了一种治疗耐药局部感染的替代方法:注射低浓度的 QDs,并应用仅包含 LED 和电池的粘性贴片。这种治疗方法可能会彻底改变烧伤、蜂窝织炎和其他皮肤感染的最后治疗手段。