Towards Optimal Design of Cancer Nanomedicines: Multi-stage Nanoparticles for the Treatment of Solid Tumors
Autor: | Stylianopoulos, Triantafyllos, Economides, Eva Athena, Baish, J. W., Fukumura, D., Jain, R. K. |
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Přispěvatelé: | Stylianopoulos, Triantafyllos [0000-0002-3093-1696], Stylianopoulos, T. [0000-0002-3093-1696] |
Rok vydání: | 2015 |
Předmět: |
Nano-carriers
Uniform distribution Secondary particles Nanoparticle Diseases paclitaxel Models Neoplasms binding affinity drug delivery system drug carrier Cytotoxicity antineoplastic agent drug release media_common Mathematical models Drug Carriers Chemistry nanoparticle Optimal systems Particle size Drug release kinetics priority journal Tumor microenvironment Drug delivery nanocarrier Chemotherapeutic drugs Drug drug design media_common.quotation_subject Biomedical Engineering Antineoplastic Agents Binding energy Enhanced permeability and retention effects chemistry Models Biological cancer chemotherapy Article process optimization Humans human Tumors Drug products Penetration (firestop) Biological biological model Targeted drug delivery Drug Design Cancer cell Biophysics Nanoparticles solid tumor Mathematical modeling Primary nanoparticles mathematical model Biomedical engineering |
Zdroj: | Annals of Biomedical Engineering Ann.Biomed.Eng. |
ISSN: | 1573-9686 0090-6964 |
Popis: | Conventional drug delivery systems for solid tumors are composed of a nano-carrier that releases its therapeutic load. These two-stage nanoparticles utilize the enhanced permeability and retention (EPR) effect to enable preferential delivery to tumor tissue. However, the size-dependency of the EPR, the limited penetration of nanoparticles into the tumor as well as the rapid binding of the particles or the released cytotoxic agents to cancer cells and stromal components inhibit the uniform distribution of the drug and the efficacy of the treatment. Here, we employ mathematical modeling to study the effect of particle size, drug release rate and binding affinity on the distribution and efficacy of nanoparticles to derive optimal design rules. Furthermore, we introduce a new multi-stage delivery system. The system consists of a 20-nm primary nanoparticle, which releases 5-nm secondary particles, which in turn release the chemotherapeutic drug. We found that tuning the drug release kinetics and binding affinities leads to improved delivery of the drug. Our results also indicate that multi-stage nanoparticles are superior over two-stage nano-carriers provided they have a faster drug release rate and for high binding affinity drugs. Furthermore, our results suggest that smaller nanoparticles achieve better treatment outcome. © 2015, Biomedical Engineering Society. 43 9 2291 2300 Cited By :25 |
Databáze: | OpenAIRE |
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