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Engineering precision nanoparticles for drug delivery
Open accessAbstract
In recent years, the development of nanoparticles has expanded into a broad range of clinical applications. Nanoparticles have been developed to overcome the limitations of free therapeutics and navigate biological barriers - systemic, microenvironmental and cellular - that are heterogeneous across patient populations and diseases. Overcoming this patient heterogeneity has also been accomplished through precision therapeutics, in which personalized interventions have enhanced therapeutic efficacy. However, nanoparticle development continues to focus on optimizing delivery platforms with a one-size-fits-all solution. As lipid-based, polymeric and inorganic nanoparticles are engineered in increasingly specified ways, they can begin to be optimized for drug delivery in a more personalized manner, entering the era of precision medicine. In this Review, we discuss advanced nanoparticle designs utilized in both non-personalized and precision applications that could be applied to improve precision therapies. We focus on advances in nanoparticle design that overcome heterogeneous barriers to delivery, arguing that intelligent nanoparticle design can improve efficacy in general delivery applications while enabling tailored designs for precision applications, thereby ultimately improving patient outcome overall.
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“The literature has shown that nanoparticles with a diameter greater than 200 nm pose a risk of activating the complement system. Particles with diameters of 50 and 200 nm can escape from the splenic space, enter the sinusoidal endothelial pores, and accumulate in large quantities at sites of liver fibrosis (29, 30).”
From Matrix mechanical remodeled carrier-free nanosystem for programmable closed-loop reversal of liver fibrosis via STING alkylation (2025) · cites this paper as [30]
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“To avoid these limitations, non‐positively charged vectors were also developed by conjugating nucleic acids into nanoparticles, which however requires complicated synthesis procedure, and the transfection efficiency is strongly affected by the size, shape, and surface environment of the nanoparticles.[ 16 ]”
From A General and Efficient Strategy for Gene Delivery Based on Tea Polyphenols Intercalation and Self‐Polymerization (2023) · cites this paper as [16]
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“To avoid these limitations, non‐positively charged vectors were also developed by conjugating nucleic acids into nanoparticles, which however requires complicated synthesis procedure, and the transfection efficiency is strongly affected by the size, shape, and surface environment of the nanoparticles.[ 16 ]”
From A General and Efficient Strategy for Gene Delivery Based on Tea Polyphenols Intercalation and Self‐Polymerization (2023) · cites this paper as [16]
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“After modification or stimulation by corresponding factors, these smart nanoparticles efficiently aggregate at the target location and release their payloads, establishing a smart treatment mode.8–12”
From Smart nanoparticles for cancer therapy (2023) · cites this paper as [9]
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“Nanoparticles taken intravenously can circulate for extended period of time with reduced clearance rates from the renal system due to their ultra-small size and superior drug loading and encapsulation efficacy.11”
From Current Advances in Chitosan Nanoparticles Based Oral Drug Delivery for Colorectal Cancer Treatment (2022) · cites this paper as [11]
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Metadata
- Authors
- Mitchell, M. J., Billingsley, M. M., Haley, R. M., Wechsler, M. E., Peppas, N. A., & Langer, R.
- Affiliations
- Abramson Cancer Center (US)
- University of Pennsylvania (US)
- The University of Texas at Austin (US)
- Corresponding author
- Mitchell, Michael J.
- Peppas, Nicholas A.
- ORCID
- Venue
- Nature Reviews Drug Discovery
- Published
- 2020-12-04
- Volume
- 20
- Issue
- 2
- Pages
- 101-124
- ISSN
- 1474-1776 (ISSN-L)
- 1474-1784
- PMC
- PMC7717100
- OpenAlex
- W3109746568
- Cited by
- 7,933
- References
- 316
- Citations by year
- 2026: 1402 · 2025: 1818 · 2024: 1723 · 2023: 1460 · 2022: 1082 · 2021: 441 · 2020: 2
- FWCI
- 49.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Reviews Drug Discovery (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (DGE-184529 8, 1845298, 1033746)
- American Association for Cancer Research (18-80-44-MITC, 18-80-44)
- American Cancer Society (129784‐IRG‐16‐188‐38‐IRG)
- Pratt Foundation
- National Institutes of Health (DP2TR002776, / NIDDK R01, / NCI R01, 5r01eb000246-20, CA016520)
- National Cancer Institute (CA016520, R01CA241661, R37CA244911, P30CA016520)
- National Institute of Allergy and Infectious Diseases (T32AI007632)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK123049)
- National Institute of Biomedical Imaging and Bioengineering (R01EB022025, R01-EB000246)
- National Center for Advancing Translational Sciences
- 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
- nanoparticles, drug delivery, precision medicine, personalized medicine, nanoparticle design, lipid nanoparticles, polymeric nanoparticles, inorganic nanoparticles, biological barriers, patient heterogeneity, targeted delivery
- MeSH terms
- Biomedical Engineering, Pharmaceutical Preparations, Humans, Drug Delivery Systems, Nanoparticles, Precision Medicine
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