Self-assembly of extracellular vesicle-like metal–organic framework nanoparticles for protection and intracellular delivery of biofunctional proteins
Abstract
The intracellular delivery of biofunctional enzymes or therapeutic proteins through systemic administration is of great importance in therapeutic intervention of various diseases. However, current strategies face substantial challenges owing to various biological barriers, including susceptibility to protein degradation and denaturation, poor cellular uptake, and low transduction efficiency into the cytosol. Here, we developed a biomimetic nanoparticle platform for systemic and intracellular delivery of proteins. Through a biocompatible strategy, guest proteins are caged in the matrix of metal-organic frameworks (MOFs) with high efficiency (up to ∼94%) and high loading content up to ∼50 times those achieved by surface conjunction, and the nanoparticles were further decorated with the extracellular vesicle (EV) membrane with an efficiency as high as ∼97%. In vitro and in vivo study manifests that the EV-like nanoparticles can not only protect proteins against protease digestion and evade the immune system clearance but also selectively target homotypic tumor sites and promote tumor cell uptake and autonomous release of the guest protein after internalization. Assisted by biomimetic nanoparticles, intracellular delivery of the bioactive therapeutic protein gelonin significantly inhibits the tumor growth in vivo and increased 14-fold the therapeutic efficacy. Together, our work not only proposes a new concept to construct a biomimetic nanoplatform but also provides a new solution for systemic and intracellular delivery of protein.
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Specific interactions (e.g., electrostatic, hydrophilic, and coordination) between the membrane of exosome and MOF matrix particles could contribute to the successful preparation of composite nanoparticles.
“some specific interactions (e.g., electrostatic, hydrophilic, and coordination) between the membrane of exosome and MOF matrix particles could contribute to the successful preparation of composite nanoparticles [58].”
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- Authors
- Cheng, G., Li, W., Ha, L., Han, X., Hao, S., Wan, Y., Wang, Z., Dong, F., Zou, X., Mao, Y., & Zheng, S.-Y.
- Affiliations
- Pennsylvania State University (US)
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2018-05-29
- Volume
- 140
- Issue
- 23
- Pages
- 7282-7291
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W2806414351
- Cited by
- 371
- References
- 57
- Citations by year
- 2026: 27 · 2025: 25 · 2024: 42 · 2023: 60 · 2022: 68 · 2021: 60 · 2020: 48 · 2019: 35 · 2018: 6
- FWCI
- 12.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the American Chemical Society (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (DP2 CA174508)
- Huck Institute of Life Sciences, Pennsylvania State University
- Materials Research Institute, Pennsylvania State University
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Organic Frameworks: Synthesis and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- metal-organic framework nanoparticles, biomimetic nanoparticles, intracellular protein delivery, gelonin, tumor-targeted delivery, immune evasion, protein encapsulation, tumor growth inhibition
- MeSH terms
- Extracellular Vesicles, Metal-Organic Frameworks, Animals, Antineoplastic Agents, Cell Membrane, Drug Carriers, Endocytosis, Humans, Neoplasms, Particle Size, Xenograft Model Antitumor Assays, Biomimetic Materials, Cell Line, Tumor, Mice, Nanoparticles, Ribosome Inactivating Proteins, Type 1
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