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一种可植入式超声供电微光源(µLight)用于光动力疗法。

An Implantable Ultrasonically-Powered Micro-Light-Source (µLight) for Photodynamic Therapy.

机构信息

Department of Electrical and Computer Engineering, Temple University, Philadelphia, PA, USA.

School of Electrical and Computer Engineering, Purdue University, West Lafayette, IN, USA.

出版信息

Sci Rep. 2019 Feb 4;9(1):1395. doi: 10.1038/s41598-019-38554-2.

Abstract

Photodynamic therapy (PDT) is a promising cancer treatment modality that can selectively target unresectable tumors through optical activation of cytotoxic agents, thus reducing many side effects associated with systemic administration of chemotherapeutic drugs. However, limited light penetration into most biological tissues have so far prevented its widespread adoption beyond dermatology and a few other oncological applications in which a fiber optic can be threaded to the desired locations via an endoscopic approach (e.g., bladder). In this paper, we introduce an ultrasonically powered implantable microlight source, μLight, which enables in-situ localized light delivery to deep-seated solid tumors. Ultrasonic powering allows for small receiver form factor (mm-scale) and power transfer deep into the tissue (several centimeters). The implants consist of piezoelectric transducers measuring 2 × 2 × 2 mm and 2 × 4 × 2 mm with surface-mounted miniature red and blue LEDs. When energized with 185 mW/cm of transmitted acoustic power at 720 kHz, μLight can generate 0.048 to 6.5 mW/cm of optical power (depending on size of the piezoelectric element and light wavelength spectrum). This allows powering multiple receivers to a distance of 10 cm at therapeutic light output levels (a delivery of 20-40 J/cm light radiation dose in 1-2 hours). In vitro tests show that HeLa cells irradiated with μLights undergo a 70% decrease in average cell viability as compared to the control group. In vivo tests in mice implanted with 4T1-induced tumors (breast cancer) show light delivery capability at therapeutic dose levels. Overall, results indicate implanting multiple µLights and operating them for 1-2 hours can achieve cytotoxicity levels comparable to the clinically reported cases using external light sources.

摘要

光动力疗法(PDT)是一种有前途的癌症治疗方法,它可以通过光学激活细胞毒性剂来选择性地靶向不可切除的肿瘤,从而减少与全身化疗药物治疗相关的许多副作用。然而,由于大多数生物组织的光穿透性有限,迄今为止,它的应用范围仅限于皮肤科和其他一些肿瘤学应用,在这些应用中,可以通过内窥镜方法(例如膀胱)将光纤穿入所需位置。在本文中,我们介绍了一种超声驱动的可植入微型光源 μLight,它可以实现对深部实体肿瘤的原位局部光输送。超声供电允许接收器具有较小的尺寸(毫米级),并且可以将功率传输到组织深处(几厘米)。这些植入物由尺寸为 2×2×2 毫米和 2×4×2 毫米的压电换能器组成,表面安装有微型红色和蓝色 LED。当在 720 kHz 时用 185 mW/cm 的传输声功率激励时,μLight 可以产生 0.048 至 6.5 mW/cm 的光功率(取决于压电元件的尺寸和光波长谱)。这允许在治疗光输出水平下将多个接收器供电到 10 cm 的距离(在 1-2 小时内输送 20-40 J/cm 的光辐射剂量)。体外测试表明,与对照组相比,用 μLights 照射的 HeLa 细胞的平均细胞活力降低了 70%。在植入 4T1 诱导的肿瘤(乳腺癌)的小鼠体内测试中,显示出在治疗剂量水平下的光输送能力。总体而言,结果表明,植入多个 μLights 并运行 1-2 小时可以达到与临床报告的使用外部光源相当的细胞毒性水平。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5764/6362227/4ec705c26888/41598_2019_38554_Fig1_HTML.jpg

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