Effect of particle size on the biodistribution, toxicity, and efficacy of drug-loaded polymeric nanoparticles in chemoradiotherapy
Open accessAbstract
Nanoparticle (NP) chemotherapeutics can improve the therapeutic index of chemoradiotherapy (CRT). However, the effect of NP physical properties, such particle size, on CRT is unknown. To address this, we examined the effects of NP size on biodistribution, efficacy and toxicity in CRT. PEG-PLGA NPs (50, 100, 150 nm mean diameters) encapsulating wotrmannin (wtmn) or KU50019 were formulated. These NP formulations were potent radiosensitizers in vitro in HT29, SW480, and lovo rectal cancer lines. In vivo, the smallest particles avoided hepatic and splenic accumulation while more homogeneously penetrating tumor xenografts than larger particles. However, smaller particles were no more effective in vivo. Instead, there was a trend toward enhanced efficacy with medium sized NPs. The smallest KU60019 particles caused more small bowel toxicity than larger particles. Our results showed that particle size significantly affects nanotherapeutics' biodistrubtion and toxicity but does not support the conclusion that smaller particles are better for this clinical application.
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Sizes from 50 nm to 100 nm are effective in preclinical models, suggesting ideal particle size distribution is necessary for efficacy of polymeric micelles.
“In some previous studies, it was shown that sizes from 50 nm–100 nm are effective in preclinical models, suggesting ideal particle size distribution is necessary for efficacy of polymeric micelles [253, 254].”
From Polymeric micelles for the delivery of poorly soluble drugs: From nanoformulation to clinical approval. (2020) · cites this paper as [253]
The Results and Discussion describe preclinical testing of 50–150 nm polymeric nanoparticles and report that they were effective radiosensitizers, with a trend toward greater efficacy at 100 nm. The paper does not establish that an ideal size distribution is necessary for efficacy, and it studies polymeric nanoparticles rather than identifying its formulations as polymeric micelles. (LLM, conf=0.84)
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- Authors
- Caster, J. M., Yu, S. K., Patel, A. N., Newman, N. J., Lee, Z. J., Warner, S. B., Wagner, K. T., Roche, K. C., Tian, X., Min, Y., & Wang, A. Z.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Caster, Joseph M.
- Venue
- Nanomedicine: Nanotechnology, Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2017-07
- Volume
- 13
- Issue
- 5
- Pages
- 1673-1683
- ISSN
- 1549-9634 (ISSN-L)
- PMC
- PMC5483200
- OpenAlex
- W2594191206
- Cited by
- 111
- References
- 31
- Citations by year
- 2026: 10 · 2025: 9 · 2024: 16 · 2023: 10 · 2022: 15 · 2021: 19 · 2020: 15 · 2019: 8 · 2018: 6 · 2017: 3
- FWCI
- 3.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nanomedicine Nanotechnology Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA178748)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Radiation Therapy and Dosimetry
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- particle size, polymeric nanoparticles, PEG-PLGA, chemoradiotherapy, radiosensitizers, wortmannin, tissue distribution, nanoparticle toxicity, small bowel toxicity, rectal cancer, tumor xenografts, nanotherapeutics
- MeSH terms
- Wortmannin, Androstadienes, Animals, Humans, Particle Size, Polymers, Rectal Neoplasms, Tissue Distribution, Mice, Nanoparticles, Chemoradiotherapy, Heterografts
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