Sequential nanoprecipitation for theranostics: Resolving assembly timescale mismatch in composite nanoparticle synthesis

IF 3.5 3区工程技术 Q2 ENGINEERING, CHEMICAL

AIChE Journal Pub Date : 2025-03-26 DOI:10.1002/aic.18817

Rachel E. Pollard, Nouha El Amri, Parker K. Lewis, Jacques Zacharie Thaddeus P. Ponce, Ashley Han, Xiuxian Li, Nathalie M. Pinkerton

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引用次数: 0

Abstract

Biomedical applications of colloidal nanocrystals (NC) have focused on nanoscale theranostics, that is, composite nanoparticles (CNP) that function as bioimaging probes while simultaneously delivering therapeutic payloads. Thus, there is a need for controlled CNP manufacturing methods that sufficiently decouple vehicle and cargo properties. Here, we investigate the assembly of poly(ethylene glycol)-b-poly(lactic acid) (PEG–PLA)-based CNPs loaded with PLA co-excipient, NCs of various sizes, and model drug molecule rubrene. We compare the established flash nanoprecipitation (FNP), a single-step method, with the emergent sequential nanoprecipitation (SNaP), a two-step method in which component addition can be temporally modulated. We find that using FNP to co-encapsulate cargo with mismatched assembly timescales yields poor CNP size control and nonuniform populations. In contrast, by delaying the CNP stabilizer addition by a few milliseconds via SNaP, we enable CNP size control, a 3-fold increase in cargo uniformity, and a 10-fold increase in co-encapsulation efficiency with rubrene.

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治疗学的顺序纳米沉淀：解决复合纳米粒子合成中组装时间尺度的不匹配

胶体纳米晶体（NC）的生物医学应用主要集中在纳米级治疗上，即复合纳米颗粒（CNP）在提供治疗有效载荷的同时充当生物成像探针。因此，需要控制CNP制造方法，使车辆和货物特性充分分离。在这里，我们研究了负载PLA共赋形剂、不同大小的nc和模型药物分子rubrene的聚乙二醇-b-聚乳酸（PEG-PLA）基CNPs的组装。我们比较了已建立的闪蒸纳米沉淀法（FNP）和紧急顺序纳米沉淀法（SNaP），后者是一种两步方法，其中成分的添加可以暂时调制。我们发现使用FNP对装配时间尺度不匹配的货物进行共封装会产生较差的CNP尺寸控制和非均匀种群。相比之下，通过SNaP将CNP稳定剂的添加延迟几毫秒，我们实现了CNP尺寸控制，货物均匀性提高了3倍，与rubrene共包效率提高了10倍。

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来源期刊

AIChE Journal 工程技术-工程：化工

CiteScore

7.10

自引率

10.80%

发文量

411

审稿时长

3.6 months

期刊介绍： The AIChE Journal is the premier research monthly in chemical engineering and related fields. This peer-reviewed and broad-based journal reports on the most important and latest technological advances in core areas of chemical engineering as well as in other relevant engineering disciplines. To keep abreast with the progressive outlook of the profession, the Journal has been expanding the scope of its editorial contents to include such fast developing areas as biotechnology, electrochemical engineering, and environmental engineering. The AIChE Journal is indeed the global communications vehicle for the world-renowned researchers to exchange top-notch research findings with one another. Subscribing to the AIChE Journal is like having immediate access to nine topical journals in the field. Articles are categorized according to the following topical areas: Biomolecular Engineering, Bioengineering, Biochemicals, Biofuels, and Food Inorganic Materials: Synthesis and Processing Particle Technology and Fluidization Process Systems Engineering Reaction Engineering, Kinetics and Catalysis Separations: Materials, Devices and Processes Soft Materials: Synthesis, Processing and Products Thermodynamics and Molecular-Scale Phenomena Transport Phenomena and Fluid Mechanics.