Numerical modeling of nanodrug distribution in tumors with heterogeneous vasculature
The distribution and accumulation of nanoparticle dosage in a tumor are important in evaluating the effectiveness of cancer treatment. The cell survival rate can quantify the therapeutic effect, and the survival rates after multiple treatments are helpful to evaluate the efficacy of a chemotherapy p...
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| Veröffentlicht in: | PloS one 2017-12, Vol.12 (12), p.e0189802-e0189802 |
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| description | The distribution and accumulation of nanoparticle dosage in a tumor are important in evaluating the effectiveness of cancer treatment. The cell survival rate can quantify the therapeutic effect, and the survival rates after multiple treatments are helpful to evaluate the efficacy of a chemotherapy plan. We developed a mathematical tumor model based on the governing equations describing the fluid flow and particle transport to investigate the drug transportation in a tumor and computed the resulting cumulative concentrations. The cell survival rate was calculated based on the cumulative concentration. The model was applied to a subcutaneous tumor with heterogeneous vascular distributions. Various sized dextrans and doxorubicin were respectively chosen as the nanodrug carrier and the traditional chemotherapeutic agent for comparison. The results showed that: 1) the largest nanoparticle drug in the current simulations yielded the highest cumulative concentration in the well vascular region, but second lowest in the surrounding normal tissues, which implies it has the best therapeutic effect to tumor and at the same time little harmful to normal tissue; 2) on the contrary, molecular chemotherapeutic agent produced the second lowest cumulative concentration in the well vascular tumor region, but highest in the surrounding normal tissue; 3) all drugs have very small cumulative concentrations in the tumor necrotic region, where drug transport is solely through diffusion. This might mean that it is hard to kill tumor stem cells hiding in it. The current model indicated that the effectiveness of the anti-tumor drug delivery was determined by the interplay of the vascular density and nanoparticle size, which governs the drug transport properties. The use of nanoparticles as anti-tumor drug carriers is generally a better choice than molecular chemotherapeutic agent because of its high treatment efficiency on tumor cells and less damage to normal tissues. |
| doi_str_mv | 10.1371/journal.pone.0189802 |
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The cell survival rate can quantify the therapeutic effect, and the survival rates after multiple treatments are helpful to evaluate the efficacy of a chemotherapy plan. We developed a mathematical tumor model based on the governing equations describing the fluid flow and particle transport to investigate the drug transportation in a tumor and computed the resulting cumulative concentrations. The cell survival rate was calculated based on the cumulative concentration. The model was applied to a subcutaneous tumor with heterogeneous vascular distributions. Various sized dextrans and doxorubicin were respectively chosen as the nanodrug carrier and the traditional chemotherapeutic agent for comparison. The results showed that: 1) the largest nanoparticle drug in the current simulations yielded the highest cumulative concentration in the well vascular region, but second lowest in the surrounding normal tissues, which implies it has the best therapeutic effect to tumor and at the same time little harmful to normal tissue; 2) on the contrary, molecular chemotherapeutic agent produced the second lowest cumulative concentration in the well vascular tumor region, but highest in the surrounding normal tissue; 3) all drugs have very small cumulative concentrations in the tumor necrotic region, where drug transport is solely through diffusion. This might mean that it is hard to kill tumor stem cells hiding in it. The current model indicated that the effectiveness of the anti-tumor drug delivery was determined by the interplay of the vascular density and nanoparticle size, which governs the drug transport properties. The use of nanoparticles as anti-tumor drug carriers is generally a better choice than molecular chemotherapeutic agent because of its high treatment efficiency on tumor cells and less damage to normal tissues.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0189802</identifier><identifier>PMID: 29287079</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Angiogenesis ; Anticancer properties ; Applied mathematics ; Biology and Life Sciences ; Biomedical engineering ; Cancer ; Cancer therapies ; Cancer treatment ; Cell survival ; Chemotherapy ; Computational fluid dynamics ; Computer simulation ; Dextrans ; Doxorubicin ; Drug carriers ; Drug delivery ; Drug delivery systems ; Drug dosages ; Engineering ; Fluid flow ; Funding ; Growth models ; Mathematical models ; Medical research ; Medicine and Health Sciences ; Nanoparticles ; Particle transport ; Pressure distribution ; Stem cells ; Survival ; Tissues ; Transport properties ; Tumor cells ; Tumors ; Vein & artery diseases</subject><ispartof>PloS one, 2017-12, Vol.12 (12), p.e0189802-e0189802</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Chou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2017 Chou et al 2017 Chou et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-d8c88a94a2ae84a2e878e8d506c1270851e6fc0fb4a11afa105cb85f8b3e76003</citedby><cites>FETCH-LOGICAL-c692t-d8c88a94a2ae84a2e878e8d506c1270851e6fc0fb4a11afa105cb85f8b3e76003</cites><orcidid>0000-0002-5737-6960</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5747441/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5747441/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29287079$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chou, Cheng-Ying</creatorcontrib><creatorcontrib>Chang, Wan-I</creatorcontrib><creatorcontrib>Horng, Tzyy-Leng</creatorcontrib><creatorcontrib>Lin, Win-Li</creatorcontrib><title>Numerical modeling of nanodrug distribution in tumors with heterogeneous vasculature</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The distribution and accumulation of nanoparticle dosage in a tumor are important in evaluating the effectiveness of cancer treatment. The cell survival rate can quantify the therapeutic effect, and the survival rates after multiple treatments are helpful to evaluate the efficacy of a chemotherapy plan. We developed a mathematical tumor model based on the governing equations describing the fluid flow and particle transport to investigate the drug transportation in a tumor and computed the resulting cumulative concentrations. The cell survival rate was calculated based on the cumulative concentration. The model was applied to a subcutaneous tumor with heterogeneous vascular distributions. Various sized dextrans and doxorubicin were respectively chosen as the nanodrug carrier and the traditional chemotherapeutic agent for comparison. The results showed that: 1) the largest nanoparticle drug in the current simulations yielded the highest cumulative concentration in the well vascular region, but second lowest in the surrounding normal tissues, which implies it has the best therapeutic effect to tumor and at the same time little harmful to normal tissue; 2) on the contrary, molecular chemotherapeutic agent produced the second lowest cumulative concentration in the well vascular tumor region, but highest in the surrounding normal tissue; 3) all drugs have very small cumulative concentrations in the tumor necrotic region, where drug transport is solely through diffusion. This might mean that it is hard to kill tumor stem cells hiding in it. The current model indicated that the effectiveness of the anti-tumor drug delivery was determined by the interplay of the vascular density and nanoparticle size, which governs the drug transport properties. The use of nanoparticles as anti-tumor drug carriers is generally a better choice than molecular chemotherapeutic agent because of its high treatment efficiency on tumor cells and less damage to normal tissues.</description><subject>Angiogenesis</subject><subject>Anticancer properties</subject><subject>Applied mathematics</subject><subject>Biology and Life Sciences</subject><subject>Biomedical engineering</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Cancer treatment</subject><subject>Cell survival</subject><subject>Chemotherapy</subject><subject>Computational fluid dynamics</subject><subject>Computer simulation</subject><subject>Dextrans</subject><subject>Doxorubicin</subject><subject>Drug carriers</subject><subject>Drug delivery</subject><subject>Drug delivery systems</subject><subject>Drug dosages</subject><subject>Engineering</subject><subject>Fluid flow</subject><subject>Funding</subject><subject>Growth models</subject><subject>Mathematical 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evaluating the effectiveness of cancer treatment. The cell survival rate can quantify the therapeutic effect, and the survival rates after multiple treatments are helpful to evaluate the efficacy of a chemotherapy plan. We developed a mathematical tumor model based on the governing equations describing the fluid flow and particle transport to investigate the drug transportation in a tumor and computed the resulting cumulative concentrations. The cell survival rate was calculated based on the cumulative concentration. The model was applied to a subcutaneous tumor with heterogeneous vascular distributions. Various sized dextrans and doxorubicin were respectively chosen as the nanodrug carrier and the traditional chemotherapeutic agent for comparison. The results showed that: 1) the largest nanoparticle drug in the current simulations yielded the highest cumulative concentration in the well vascular region, but second lowest in the surrounding normal tissues, which implies it has the best therapeutic effect to tumor and at the same time little harmful to normal tissue; 2) on the contrary, molecular chemotherapeutic agent produced the second lowest cumulative concentration in the well vascular tumor region, but highest in the surrounding normal tissue; 3) all drugs have very small cumulative concentrations in the tumor necrotic region, where drug transport is solely through diffusion. This might mean that it is hard to kill tumor stem cells hiding in it. The current model indicated that the effectiveness of the anti-tumor drug delivery was determined by the interplay of the vascular density and nanoparticle size, which governs the drug transport properties. The use of nanoparticles as anti-tumor drug carriers is generally a better choice than molecular chemotherapeutic agent because of its high treatment efficiency on tumor cells and less damage to normal tissues.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29287079</pmid><doi>10.1371/journal.pone.0189802</doi><tpages>e0189802</tpages><orcidid>https://orcid.org/0000-0002-5737-6960</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Angiogenesis Anticancer properties Applied mathematics Biology and Life Sciences Biomedical engineering Cancer Cancer therapies Cancer treatment Cell survival Chemotherapy Computational fluid dynamics Computer simulation Dextrans Doxorubicin Drug carriers Drug delivery Drug delivery systems Drug dosages Engineering Fluid flow Funding Growth models Mathematical models Medical research Medicine and Health Sciences Nanoparticles Particle transport Pressure distribution Stem cells Survival Tissues Transport properties Tumor cells Tumors Vein & artery diseases |
| title | Numerical modeling of nanodrug distribution in tumors with heterogeneous vasculature |
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