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.
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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