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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Nanoparticles with a diameter greater than 200 nm pose a risk of activating the complement system, and particles with diameters of 50 and 200 nm can escape from the splenic space, enter sinusoidal endothelial pores, and accumulate in large quantities at sites of liver fibrosis.
“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]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredTransfection efficiency of non-positively charged nanoparticle vectors is strongly affected by the size, shape, and surface environment of the nanoparticles.
“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]
The Biological barriers > Cellular and intracellular barriers section says nanoparticle size, shape, charge and surface interactions affect cellular uptake, including uptake pathways for negatively charged particles. It does not establish that these factors strongly affect transfection efficiency specifically for non-positively charged nucleic-acid vectors. Page numbers are not provided in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredNon-positively charged vectors developed by conjugating nucleic acids into nanoparticles require complicated synthesis procedure.
“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]
The ‘Intracellular targeting’ section describes nucleic acids complexed with cationic materials, not non-positively charged vectors made by conjugation. The ‘Lipid-based NPs’ section describes near-neutral ionizable particles but calls their synthesis simple; it does not establish whether the conjugated vectors in the claim require complicated synthesis. Searches for non-positive charge, nucleic-acid conjugation, and synthesis complexity found no passage addressing that specific claim. (LLM, conf=0.74)
Experimental — accuracy not yet measuredAfter modification or stimulation by corresponding factors, smart nanoparticles efficiently aggregate at the target location and release their payloads.
“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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- 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 · 2014: 1
- 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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