Principles of nanoparticle design for overcoming biological barriers to drug delivery
Open accessAbstract
Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery.
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Nanoparticles will accumulate in the liver if their sizes are comparable to the size of vascular fenestration of the liver (50-100 nm) or end up in the spleen if their sizes are close to interendothelial cell slits of the spleen (100-200 nm).
“Nanoparticles will accumulate in the liver if their sizes are comparable to the size of vascular fenestration of the liver (50–100 nm) or end up in the spleen if their sizes are close to interendothelial cell slits of the spleen (100–200 nm).217”
From The Pursuit of Shortwave Infrared-Emitting Nanoparticles with Bright Fluorescence through Molecular Design and Excited-State Engineering of Molecular Aggregates (2022) · cites this paper as [217]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredComplicated modifications are always needed to ensure that nanoparticles produced are blood-brain barrier-permeable.
“Crossing the BBB with various nanoparticles, such as liposomes, cationic polymers, inorganic nanoparticles, and nanocapsules, has shown promise in delivery of various cargos into the CNS, but complicated modifications are always needed to ensure that the particles produced are BBB-permeable (15, 18, 19).”
From Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection (2020) · cites this paper as [18]
The Opsonization/sequestration section reports that polysorbate 80–coated nanoparticles enhanced drug delivery across the blood-brain barrier. That supports an example of a modification that aided crossing, but the paper does not say complicated modifications are always necessary to make nanoparticles BBB-permeable. (LLM, conf=0.85)
Experimental — accuracy not yet measuredCrossing the blood-brain barrier with nanoparticles such as liposomes, cationic polymers, inorganic nanoparticles, and nanocapsules has shown promise in delivery of various cargos into the CNS.
“Crossing the BBB with various nanoparticles, such as liposomes, cationic polymers, inorganic nanoparticles, and nanocapsules, has shown promise in delivery of various cargos into the CNS, but complicated modifications are always needed to ensure that the particles produced are BBB-permeable (15, 18, 19).”
From Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection (2020) · cites this paper as [18]
The section on opsonization and sequestration reports enhanced drug delivery across the blood-brain barrier using polysorbate-coated poly(butyl cyanoacrylate) nanoparticles. It does not establish BBB delivery for the full list of liposomes, cationic polymers, inorganic nanoparticles, and nanocapsules, or for various cargos into the CNS. No page number is available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredCrossing the BBB with various nanoparticles has shown promise in delivery of various cargos into the CNS, but complicated modifications are always needed to ensure that the particles produced are BBB-permeable.
“Among a number of approaches, crossing the BBB with various nanoparticles has shown promise in delivery of various cargos into the CNS, but complicated modifications are always needed to ensure that the particles produced are BBB-permeable (15, 18, 19).”
From Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection (2020) · cites this paper as [18]
The Opsonization/sequestration section (page unavailable) reports enhanced drug delivery beyond the blood–brain barrier using polysorbate-80-coated nanoparticles. It does not establish delivery of various cargos into the CNS or that complicated modifications are always necessary for BBB permeability. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe zeta potential of NP-Pep suspended in 0.1× PBS buffer (pH 7.4) is ~−38 mV.
“To demonstrate the colloidal stability of the NP-Pep, we determined the zeta potential (ζ-potential) of the NP-Pep suspended in 0.1× PBS buffer (pH 7.4) to be ~−38 mV, which has been previously shown to be both ideal for serum protein applications and sufficient for electrostatic repulsive forces to dominate over the van der Waals force, such that agglomeration is suppressed (Supplementary Fig. 11”
From Nanoproteomics enables proteoform-resolved analysis of low-abundance proteins in human serum (2020) · cites this paper as [45]
Nanomaterial properties such as size, geometry, material composition and surface chemistry can greatly influence the interactions of the nanomaterials with biological systems.
“For example, nanomaterial properties such as size, geometry, material composition and surface chemistry can greatly influence the interactions of the nanomaterials with biological systems49,50.”
From How to design preclinical studies in nanomedicine and cell therapy to maximize the prospects of clinical translation (2018) · cites this paper as [49]
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BackgroundAdvances in Magnetic Nanoparticles for Biomedical Applications
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BackgroundSafety Assessment of Graphene-Based Materials: Focus on Human Health and the Environment
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- Authors
- Blanco, E., Shen, H., & Ferrari, M.
- Affiliations
- Houston Methodist (US)
- Venue
- Nature Biotechnology
- Published
- 2015-09
- Volume
- 33
- Issue
- 9
- Pages
- 941-951
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC4978509
- OpenAlex
- W2143463421
- Cited by
- 7,002
- References
- 123
- Citations by year
- 2026: 729 · 2025: 685 · 2024: 772 · 2023: 712 · 2022: 739 · 2021: 713 · 2020: 736 · 2019: 652 · 2018: 611 · 2017: 436 · 2016: 198 · 2015: 15 · 2014: 1
- FWCI
- 150.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (U54CA151668, U54CA143837)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- nanoparticle drug delivery, nanocarrier design, biological barriers, local drug delivery, intravenous administration, tumor accumulation, cancer therapeutics, inflammation, nanotherapeutics
- MeSH terms
- Biocompatible Materials, Drug Compounding, Drug Design, Nanomedicine, Nanocapsules
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