Single- particle imaging of nanomedicine entering the brain

• 成果类型: Article
• 署名作者: Wei, Mian; Qian, Naixin; Gao, Xin; Lang, Xiaoqi; Song, Donghui; Min, Wei
• 署名单位: Columbia University; Columbia University; Columbia University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13749
• DOI: 10.1073/pnas.2309811121
• 发表日期: 2024-01-30
• 关键词: stimulated raman-scattering; poly(butyl cyanoacrylate) nanoparticles; central-nervous-system; drug-delivery; barrier; disease; cns; nanocarriers; surfactant; microscopy

摘要

Nanomedicine has emerged as a revolutionary strategy of drug delivery. However, fundamentals of the nano-neuro interaction are elusive. In particular, whether nanocarriers can cross the blood-brain barrier (BBB) and release the drug cargo inside the brain, a basic process depicted in numerous books and reviews, remains controversial. Here, we develop an optical method, based on stimulated Raman scattering, for imaging nanocarriers in tissues. Our method achieves a suite of capabilities-single- particle sensitivity, chemical specificity, and particle counting capability. With this method, we visualize individual intact nanocarriers crossing the BBB of mouse brains and quantify the absolute number by particle counting. The fate of nanocarriers after crossing the BBB shows remarkable heterogeneity across multiple scales. With a mouse model of aging, we find that blood-brain transport of nanocarriers decreases with age substantially. This technology would facilitate development of effective therapeutics for brain diseases and clinical translation of nanocarrier-based treatment in general. Significance Drug delivery via nanocarriers is a groundbreaking approach. However, the in vivo behaviors of these nanocarriers remain largely unknown due to the lack of techniques. Here, we develop an optical method to image nanocarriers in tissues. Our method offers unique advantages including singleparticle sensitivity, chemical specificity, and particle counting capability. With this method, we observe individual nanocarriers that cross the blood-brain barrier and count their absolute number in the brain. We find that the fate of nanocarriers varies substantially across multiple scales and the transport of nanocarriers to the brain decreases with age. This technology has the potential to greatly advance the development and translation of nanocarrierbased treatment.