为什么闪式纳米沉淀的内部结构二十年说不清#

闪式纳米沉淀（FNP）用受限撞击射流（CIJ）把有机相和水相在毫秒内混合，让疏水分子瞬间过饱和、聚集成纳米粒，能连续、低能耗地做出超高载药量颗粒。但“混合”和“聚集”两个过程在微秒到毫秒尺度上赛跑，谁快谁慢决定颗粒内部是均匀互溶还是相分离，这些特征时间此前很难直接测，结构调控规则一直不清楚。本文想用AIE分子做探针，把这场竞争量化。

Hypothesis of the competition between τ BCP-agg with τ SM-agg and the path selection, determining the internal structure, the particle size, and the size stability of the formed particle. Note: The structure of clusters and particles is in 2D view of a cross section; The structure does not indicate a real number and size of the clusters and a real evenness of the chemical components, which can vary in specific cases.

荧光和粒径如何读出内部结构#

作者把疏水AIE分子TPE与mPEG-b-PLGA在CIJ混合器中共沉淀，系统改变PLGA嵌段分子量（约1k到50k）和混合雷诺数（Re 109–872）。TPE聚集才发光，荧光强弱可间接反映TPE与聚合物是否分子级相邻。结果显示，所有嵌段分子量下荧光都增强，说明TPE与BCP均匀分布，初始粒径都在100–120 nm；改变分子量没能有效调节内部结构，但亲水/疏水嵌段比影响稳定性，PLGA过大时颗粒一天内长到1 μm。粒径在Re约400后收敛到约100 nm，但荧光在Re约168和约546出现两次转变，说明粒径收敛不代表内部结构均匀，后者需要更高Re。混合时间超过约287 ms后，标度关系可能不再准确，区域D的绝对值不可靠。XPS只测表面5–10 nm，内部结构主要靠荧光间接推断。

A-c) the initial particle size distribution (in5 min after the preparation) and d-f) the size stability of mPEG-b-PLGA(3.0 μg/mL)/TPE(3.0 μg/mL) nanoparticles with various M w of mPEG-b-PLGA. (* indicates the particle can be observed by eyes which was much larger than 1 μm).

Hypothesis of the competition between τ mix with τ MC-agg determining the internal structure, the particle size, and the size stability of the formed particle (e.g., mPEG(4.9 k)-b-PLGA(9.9 k)(3.0 μg/mL)/TPE(3.0 μg/mL) particles). Note: The structure of clusters and particles is in 2D view of a cross section; The structure does not indicate a real number and size of the clusters and a real evenness of the chemical components, which can vary in specific cases.

能用到哪一步#

这项工作把FNP从经验试错变成可量化的时间尺度选择规则，给纳米药物、农药和储能材料的制造者提供了一条“先调混合、再调配方”的路径。但结论依赖TPE荧光这一间接探针和THF/水/mPEG-b-PLGA这一特定体系，其他溶剂、聚合物或低过饱和条件是否适用，原文只是推测。它更像一个机理框架，而不是可直接放大的工艺包。