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通过微针贴片递送至皮肤的生物相容性近红外量子点记录疫苗接种情况。

Biocompatible near-infrared quantum dots delivered to the skin by microneedle patches record vaccination.

作者信息

McHugh Kevin J, Jing Lihong, Severt Sean Y, Cruz Mache, Sarmadi Morteza, Jayawardena Hapuarachchige Surangi N, Perkinson Collin F, Larusson Fridrik, Rose Sviatlana, Tomasic Stephanie, Graf Tyler, Tzeng Stephany Y, Sugarman James L, Vlasic Daniel, Peters Matthew, Peterson Nels, Wood Lowell, Tang Wen, Yeom Jihyeon, Collins Joe, Welkhoff Philip A, Karchin Ari, Tse Megan, Gao Mingyuan, Bawendi Moungi G, Langer Robert, Jaklenec Ana

机构信息

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.

Key Laboratory of Colloid, Interface and Chemical Thermodynamics, Institute of Chemistry, Chinese Academy of Sciences, Bei Yi Jie 2, Zhong Guan Cun, Beijing 100190, China.

出版信息

Sci Transl Med. 2019 Dec 18;11(523). doi: 10.1126/scitranslmed.aay7162.

Abstract

Accurate medical recordkeeping is a major challenge in many low-resource settings where well-maintained centralized databases do not exist, contributing to 1.5 million vaccine-preventable deaths annually. Here, we present an approach to encode medical history on a patient using the spatial distribution of biocompatible, near-infrared quantum dots (NIR QDs) in the dermis. QDs are invisible to the naked eye yet detectable when exposed to NIR light. QDs with a copper indium selenide core and aluminum-doped zinc sulfide shell were tuned to emit in the NIR spectrum by controlling stoichiometry and shelling time. The formulation showing the greatest resistance to photobleaching after simulated sunlight exposure (5-year equivalence) through pigmented human skin was encapsulated in microparticles for use in vivo. In parallel, microneedle geometry was optimized in silico and validated ex vivo using porcine and synthetic human skin. QD-containing microparticles were then embedded in dissolvable microneedles and administered to rats with or without a vaccine. Longitudinal in vivo imaging using a smartphone adapted to detect NIR light demonstrated that microneedle-delivered QD patterns remained bright and could be accurately identified using a machine learning algorithm 9 months after application. In addition, codelivery with inactivated poliovirus vaccine produced neutralizing antibody titers above the threshold considered protective. These findings suggest that intradermal QDs can be used to reliably encode information and can be delivered with a vaccine, which may be particularly valuable in the developing world and open up new avenues for decentralized data storage and biosensing.

摘要

在许多资源匮乏的地区,准确的医疗记录保存是一项重大挑战,这些地区不存在维护良好的中央数据库,这每年导致150万例可通过疫苗预防的死亡。在此,我们提出一种方法,利用真皮中生物相容性近红外量子点(NIR QDs)的空间分布对患者的病史进行编码。量子点肉眼不可见,但在近红外光照射下可被检测到。通过控制化学计量和包覆时间,对具有硒化铜铟核心和铝掺杂硫化锌壳层的量子点进行调整,使其在近红外光谱中发射。在模拟阳光照射(相当于5年)后,通过有色人种皮肤表现出对光漂白具有最大抗性的制剂被封装在微粒中用于体内。同时,在计算机上对微针几何形状进行了优化,并使用猪皮和合成人皮进行了体外验证。然后将含有量子点的微粒嵌入可溶解的微针中,并给有或没有接种疫苗的大鼠给药。使用适配检测近红外光的智能手机进行纵向体内成像表明,微针递送的量子点图案在应用9个月后仍保持明亮,并且可以使用机器学习算法准确识别。此外,与灭活脊髓灰质炎疫苗共同递送产生的中和抗体滴度高于保护性阈值。这些发现表明,皮内量子点可用于可靠地编码信息,并可与疫苗一起递送,这在发展中国家可能特别有价值,并为分散式数据存储和生物传感开辟了新途径。

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