Stimuli-sensitive nano-drug delivery with programmable size changes to enhance accumulation of therapeutic agents in tumors
Nano-based drug delivery systems hold significant promise for cancer therapies. Presently, the poor accumulation of drug-carrying nanoparticles in tumors has limited their success. In this study, based on a combination of the paradigms of intravascular and extravascular drug release, an efficient nanosized drug delivery system with programmable size changes is introduced. Drug-loaded smaller nanoparticles (secondary nanoparticles), which are loaded inside larger nanoparticles (primary nanoparticles), are released within the microvascular network due to temperature field resulting from focused ultrasound. This leads to the scale of the drug delivery system decreasing by 7.5 to 150 times. Subsequently, smaller nanoparticles enter the tissue at high transvascular rates and achieve higher accumulation, leading to higher penetration depths. In response to the acidic pH of tumor microenvironment (according to the distribution of oxygen), they begin to release the drug doxorubicin at very slow rates (i.e., sustained release). To predict the performance and distribution of therapeutic agents, a semi-realistic microvascular network is first generated based on a sprouting angiogenesis model and the transport of therapeutic agents is then investigated based on a developed multi-compartment model. The results show that reducing the size of the primary and secondary nanoparticles can lead to higher cell death rate. In addition, tumor growth can be inhibited for a longer time by enhancing the bioavailability of the drug in the extracellular space. The proposed drug delivery system can be very promising in clinical applications. Furthermore, the proposed mathematical model is applicable to broader applications to predict the performance of drug delivery systems.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:30 |
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| Enthalten in: |
Drug delivery - 30(2023), 1 vom: 14. Dez., Seite 2186312 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Souri, Mohammad [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 13.03.2023 Date Revised 17.03.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.1080/10717544.2023.2186312 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Nano-based drug delivery systems hold significant promise for cancer therapies. Presently, the poor accumulation of drug-carrying nanoparticles in tumors has limited their success. In this study, based on a combination of the paradigms of intravascular and extravascular drug release, an efficient nanosized drug delivery system with programmable size changes is introduced. Drug-loaded smaller nanoparticles (secondary nanoparticles), which are loaded inside larger nanoparticles (primary nanoparticles), are released within the microvascular network due to temperature field resulting from focused ultrasound. This leads to the scale of the drug delivery system decreasing by 7.5 to 150 times. Subsequently, smaller nanoparticles enter the tissue at high transvascular rates and achieve higher accumulation, leading to higher penetration depths. In response to the acidic pH of tumor microenvironment (according to the distribution of oxygen), they begin to release the drug doxorubicin at very slow rates (i.e., sustained release). To predict the performance and distribution of therapeutic agents, a semi-realistic microvascular network is first generated based on a sprouting angiogenesis model and the transport of therapeutic agents is then investigated based on a developed multi-compartment model. The results show that reducing the size of the primary and secondary nanoparticles can lead to higher cell death rate. In addition, tumor growth can be inhibited for a longer time by enhancing the bioavailability of the drug in the extracellular space. The proposed drug delivery system can be very promising in clinical applications. Furthermore, the proposed mathematical model is applicable to broader applications to predict the performance of drug delivery systems | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a cancer nanomedicine | |
| 650 | 4 | |a focused ultrasound | |
| 650 | 4 | |a hyperthermia | |
| 650 | 4 | |a multi-stage delivery system | |
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| 700 | 1 | |a Kiani Shahvandi, Mohammad |e verfasserin |4 aut | |
| 700 | 1 | |a Chiani, Mohsen |e verfasserin |4 aut | |
| 700 | 1 | |a Moradi Kashkooli, Farshad |e verfasserin |4 aut | |
| 700 | 1 | |a Farhangi, Ali |e verfasserin |4 aut | |
| 700 | 1 | |a Mehrabi, Mohammad Reza |e verfasserin |4 aut | |
| 700 | 1 | |a Rahmim, Arman |e verfasserin |4 aut | |
| 700 | 1 | |a Savage, Van M |e verfasserin |4 aut | |
| 700 | 1 | |a Soltani, M |e verfasserin |4 aut | |
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