Unlocking intracellular protein delivery by harnessing polymersomes synthesized at microliter volumes using Photo‐PISA
Author(s)
Type
Journal Article
Abstract
Efficient delivery of therapeutic proteins and vaccine antigens to intracellular targets is challenging due to generally poor cell membrane permeation and endolysosomal entrapment causing degradation. Herein, these challenges are addressed by developing an oxygen-tolerant photoinitiated polymerization-induced self-assembly (Photo-PISA) process, allowing for the microliter-scale (10 µL) synthesis of protein-loaded polymersomes directly in 1536-well plates. High-resolution techniques capable of analysis at a single particle level are employed to analyze protein encapsulation and release mechanisms. Using confocal microscopy and super-resolution stochastic optical reconstruction microscopy (STORM) imaging, their ability to deliver proteins into the cytosol following endosomal escape is subsequently visualized. Lastly, the adaptability of these polymersomes is exploited to encapsulate and deliver a prototype vaccine antigen, demonstrating its ability to activate antigen-presenting cells and support antigen cross-presentation for applications in subunit vaccines and cancer immunotherapy. This combination of ultralow volume synthesis and efficient intracellular delivery holds significant promise for unlocking the high throughput screening of a broad range of otherwise cost-prohibitive or early-stage therapeutic protein and vaccine antigen candidates that can be difficult to obtain in large quantities. The versatility of this platform for rapid screening of intracellular protein delivery can result in significant advancements across the fields of nanomedicine and biomedical engineering.
Date Issued
2024-12-05
Date Acceptance
2024-10-04
Citation
Advanced Materials, 2024, 36 (49)
ISSN
0935-9648
Publisher
Wiley
Journal / Book Title
Advanced Materials
Volume
36
Issue
49
Copyright Statement
© 2024 The Author(s). Advanced Materials published by Wiley-VCH GmbH This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/39417762
Subjects
Science & Technology
Physical Sciences
Technology
Chemistry, Multidisciplinary
Chemistry, Physical
Nanoscience & Nanotechnology
Materials Science, Multidisciplinary
Physics, Applied
Physics, Condensed Matter
Chemistry
Science & Technology - Other Topics
Materials Science
Physics
intracellular delivery
pH responsive
polymerization-induced self-assembly
polymersomes
protein delivery
RESPONSIVE POLYMERSOMES
CROSS-PRESENTATION
ENDOSOMAL ESCAPE
LIGHT
NANOREACTOR
VESICLES
ANTIGENS
Publication Status
Published
Coverage Spatial
Germany
Article Number
2408000
Date Publish Online
2024-10-17