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Nanotechnology for protein delivery: Overview and perspectives
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Protein-based therapeutics have made a significant impact in the treatment of a variety of important human diseases. However, given their intrinsically vulnerable structure and susceptibility to enzymatic degradation, many therapeutic proteins such as enzymes, growth factors, hormones, and cytokines suffer from poor physicochemical/biological stability and immunogenicity that may limit their potential benefits, and in some cases limit their utility. Furthermore, when protein therapeutics are developed for intracellular targets, their internalization and biological activity may be limited by inefficient membrane permeability and/or endosomal escape. Development of effective protein delivery strategies is therefore essential to further enhance therapeutic outcomes to enable widespread medical applications. This review discusses the advantages and limitations of marketed and developmental-stage protein delivery strategies, and provides a focused overview of recent advances in nanotechnology platforms for the systemic delivery of therapeutic proteins. In addition, we also highlight nanoparticle-mediated non-invasive administration approaches (e.g., oral, nasal, pulmonary, and transdermal routes) for protein delivery.
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“Delivery of proteins such as catalase raises a few concerns such as its instability in vivo due to the presence of numerous physiological proteases, unpredictable protein immunogenicity, and poor in vivo half-life.27,28”
From Catalase-Integrated Hyaluronic Acid as Nanocarriers for Enhanced Photodynamic Therapy in Solid Tumor (2019) · cites this paper as [27]
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Chaudhari, P., Basavaraj, B. V., & Mallya, P. (2026) · Nanomedicine and nanotoxicology · doi:10.1007/978-3-032-29006-9_13
Metadata
- Authors
- Yu, M., Wu, J., Shi, J., & Farokhzad, O. C.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Shi, Jinjun
- Farokhzad, Omid C.
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2016-10
- Volume
- 240
- Pages
- 24-37
- ISSN
- 0168-3659 (ISSN-L)
- PMC
- PMC4833694
- OpenAlex
- W2173147935
- Cited by
- 410
- References
- 138
- Citations by year
- 2026: 29 · 2025: 47 · 2024: 34 · 2023: 40 · 2022: 44 · 2021: 65 · 2020: 47 · 2019: 48 · 2018: 26 · 2017: 21 · 2016: 9
- FWCI
- 1.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- Funders
- National Institutes of Health (NIH) (EB015419, R00CA160350, U54-CA151884)
- Movember-Prostate Cancer Foundation (PCF)
- National Research Foundation of Korea (K1A1A2048701)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- protein delivery, nanotechnology, therapeutic proteins, nanoparticle drug delivery, systemic drug delivery, intracellular delivery, endosomal escape, membrane permeability, protein stability, immunogenicity, oral drug delivery, intranasal drug delivery, pulmonary drug delivery, transdermal drug delivery
- MeSH terms
- Animals, Humans, Proteins, Tissue Distribution, Drug Delivery Systems, Nanotechnology, Nanoparticles
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