Blockade of CD73 using siRNA loaded chitosan lactate nanoparticles functionalized with TAT-hyaluronate enhances doxorubicin mediated cytotoxicity in cancer cells both in vitro and in vivo
Chemotherapy drugs are still one of the first treatment options used in many cancers; however, problems such as cytotoxic side effects on normal cells after systemic administration and resistance to treatment have reduced the use of chemotherapeutics day by day. Targeted delivery of these drugs to t...
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| Veröffentlicht in: | International journal of biological macromolecules 2021-09, Vol.186, p.849-863 |
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| creator | Salehi Khesht, Armin Mahmoud Karpisheh, Vahid Sahami Gilan, Parisa Melnikova, Lyubov A. Olegovna Zekiy, Angelina Mohammadi, Mahdis Hojjat-Farsangi, Mohammad Majidi Zolbanin, Naime Mahmoodpoor, Ata Hassannia, Hadi Aghebati-Maleki, Leili Jafari, Reza Jadidi-Niaragh, Farhad |
| description | Chemotherapy drugs are still one of the first treatment options used in many cancers; however, problems such as cytotoxic side effects on normal cells after systemic administration and resistance to treatment have reduced the use of chemotherapeutics day by day. Targeted delivery of these drugs to the tumor site and sensitization of cancer cells to death induced by chemotherapy drugs are ways that can overcome the limitations of the use of these drugs. In this study, we designed and generated a novel nanocarrier composed of chitosan lactate nanoparticles (NPs) functionalized by HIV-1 derived TAT peptide (Transactivating transcriptional activator) and hyaluronate (HA) to deliver CD73 siRNA and doxorubicin to 4T1 and CT26 cancer cells, both in vivo and in vitro, as a novel combinatorial treatment strategy. The CD73 molecule plays a key role in many cancer cell behaviors such as proliferation, angiogenesis, metastasis, imunosuppression, and resistance to chemotherapy. Therefore, we decided to reduce the side effects of DOX by simultaneously transmitting CD73 siRNA and DOX by CL-TAT-HA NPs, increase the susceptibility of cancer cells to DOX-induced cell death, and stimulate anti-tumor immune responses, for the first time. These results indicated that simultaneous transfer of CD73 siRNA and DOX to cancer cells (4 T1 and CT26) increased cell death and inhibited the prolifration and spread of cancer cells. Also, the preferential aggregation of NPs in the tumor microenvironment reduced tumor growh, promoted the survival of tumor-bearing mice, and induced anti-tumor immune responses. These findings indicate that CL-TAT-HA NPs are a good candidate for targeted siRNA/drug delivery to cancer cells and the simultaneous transfer of CD73 siRNA and DOX to cancer cells using this nanocarrier can be used to treat cancer. |
| doi_str_mv | 10.1016/j.ijbiomac.2021.07.034 |
| format | Article |
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Targeted delivery of these drugs to the tumor site and sensitization of cancer cells to death induced by chemotherapy drugs are ways that can overcome the limitations of the use of these drugs. In this study, we designed and generated a novel nanocarrier composed of chitosan lactate nanoparticles (NPs) functionalized by HIV-1 derived TAT peptide (Transactivating transcriptional activator) and hyaluronate (HA) to deliver CD73 siRNA and doxorubicin to 4T1 and CT26 cancer cells, both in vivo and in vitro, as a novel combinatorial treatment strategy. The CD73 molecule plays a key role in many cancer cell behaviors such as proliferation, angiogenesis, metastasis, imunosuppression, and resistance to chemotherapy. Therefore, we decided to reduce the side effects of DOX by simultaneously transmitting CD73 siRNA and DOX by CL-TAT-HA NPs, increase the susceptibility of cancer cells to DOX-induced cell death, and stimulate anti-tumor immune responses, for the first time. These results indicated that simultaneous transfer of CD73 siRNA and DOX to cancer cells (4 T1 and CT26) increased cell death and inhibited the prolifration and spread of cancer cells. Also, the preferential aggregation of NPs in the tumor microenvironment reduced tumor growh, promoted the survival of tumor-bearing mice, and induced anti-tumor immune responses. These findings indicate that CL-TAT-HA NPs are a good candidate for targeted siRNA/drug delivery to cancer cells and the simultaneous transfer of CD73 siRNA and DOX to cancer cells using this nanocarrier can be used to treat cancer.</description><identifier>ISSN: 0141-8130</identifier><identifier>ISSN: 1879-0003</identifier><identifier>EISSN: 1879-0003</identifier><identifier>DOI: 10.1016/j.ijbiomac.2021.07.034</identifier><identifier>PMID: 34245737</identifier><language>eng</language><publisher>AMSTERDAM: Elsevier B.V</publisher><subject>5'-Nucleotidase - genetics ; 5'-Nucleotidase - metabolism ; Animals ; Antibiotics, Antineoplastic - chemistry ; Antibiotics, Antineoplastic - pharmacology ; Antibiotics, Antineoplastic - toxicity ; Apoptosis - drug effects ; Biochemistry & Molecular Biology ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Breast Neoplasms - therapy ; Cancer ; CD73 ; Cell Line, Tumor ; Cell Movement - drug effects ; Cell Proliferation - drug effects ; Chemistry ; Chemistry, Applied ; Chitosan - analogs & derivatives ; Chitosan - chemistry ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - metabolism ; Colorectal Neoplasms - pathology ; Colorectal Neoplasms - therapy ; Doxorubicin ; Doxorubicin - chemistry ; Doxorubicin - pharmacology ; Doxorubicin - toxicity ; Drug Compounding ; Female ; GPI-Linked Proteins - genetics ; GPI-Linked Proteins - metabolism ; Hyaluronic Acid - chemistry ; Life Sciences & Biomedicine ; Medicin och hälsovetenskap ; Mice ; Mice, Inbred BALB C ; Nanoparicle ; Nanoparticles ; Nanotechnology ; Neoplasm Invasiveness ; Neovascularization, Pathologic ; Physical Sciences ; Polymer Science ; RNA, Small Interfering - chemistry ; RNA, Small Interfering - genetics ; RNA, Small Interfering - metabolism ; RNAi Therapeutics ; Science & Technology ; siRNA ; tat Gene Products, Human Immunodeficiency Virus - chemistry</subject><ispartof>International journal of biological macromolecules, 2021-09, Vol.186, p.849-863</ispartof><rights>2021</rights><rights>Copyright © 2021. Published by Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>28</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000688462000001</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c456t-63f8e9116f81a53856c1d2f268faa6d242e7b26555b27bf58692727d2a4b372c3</citedby><cites>FETCH-LOGICAL-c456t-63f8e9116f81a53856c1d2f268faa6d242e7b26555b27bf58692727d2a4b372c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ijbiomac.2021.07.034$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,315,781,785,886,3551,27929,27930,39263,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34245737$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:147425041$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Salehi Khesht, Armin Mahmoud</creatorcontrib><creatorcontrib>Karpisheh, Vahid</creatorcontrib><creatorcontrib>Sahami Gilan, Parisa</creatorcontrib><creatorcontrib>Melnikova, Lyubov A.</creatorcontrib><creatorcontrib>Olegovna Zekiy, Angelina</creatorcontrib><creatorcontrib>Mohammadi, Mahdis</creatorcontrib><creatorcontrib>Hojjat-Farsangi, Mohammad</creatorcontrib><creatorcontrib>Majidi Zolbanin, Naime</creatorcontrib><creatorcontrib>Mahmoodpoor, Ata</creatorcontrib><creatorcontrib>Hassannia, Hadi</creatorcontrib><creatorcontrib>Aghebati-Maleki, Leili</creatorcontrib><creatorcontrib>Jafari, Reza</creatorcontrib><creatorcontrib>Jadidi-Niaragh, Farhad</creatorcontrib><title>Blockade of CD73 using siRNA loaded chitosan lactate nanoparticles functionalized with TAT-hyaluronate enhances doxorubicin mediated cytotoxicity in cancer cells both in vitro and in vivo</title><title>International journal of biological macromolecules</title><addtitle>INT J BIOL MACROMOL</addtitle><addtitle>Int J Biol Macromol</addtitle><description>Chemotherapy drugs are still one of the first treatment options used in many cancers; however, problems such as cytotoxic side effects on normal cells after systemic administration and resistance to treatment have reduced the use of chemotherapeutics day by day. Targeted delivery of these drugs to the tumor site and sensitization of cancer cells to death induced by chemotherapy drugs are ways that can overcome the limitations of the use of these drugs. In this study, we designed and generated a novel nanocarrier composed of chitosan lactate nanoparticles (NPs) functionalized by HIV-1 derived TAT peptide (Transactivating transcriptional activator) and hyaluronate (HA) to deliver CD73 siRNA and doxorubicin to 4T1 and CT26 cancer cells, both in vivo and in vitro, as a novel combinatorial treatment strategy. The CD73 molecule plays a key role in many cancer cell behaviors such as proliferation, angiogenesis, metastasis, imunosuppression, and resistance to chemotherapy. Therefore, we decided to reduce the side effects of DOX by simultaneously transmitting CD73 siRNA and DOX by CL-TAT-HA NPs, increase the susceptibility of cancer cells to DOX-induced cell death, and stimulate anti-tumor immune responses, for the first time. These results indicated that simultaneous transfer of CD73 siRNA and DOX to cancer cells (4 T1 and CT26) increased cell death and inhibited the prolifration and spread of cancer cells. Also, the preferential aggregation of NPs in the tumor microenvironment reduced tumor growh, promoted the survival of tumor-bearing mice, and induced anti-tumor immune responses. These findings indicate that CL-TAT-HA NPs are a good candidate for targeted siRNA/drug delivery to cancer cells and the simultaneous transfer of CD73 siRNA and DOX to cancer cells using this nanocarrier can be used to treat cancer.</description><subject>5'-Nucleotidase - genetics</subject><subject>5'-Nucleotidase - metabolism</subject><subject>Animals</subject><subject>Antibiotics, Antineoplastic - chemistry</subject><subject>Antibiotics, Antineoplastic - pharmacology</subject><subject>Antibiotics, Antineoplastic - toxicity</subject><subject>Apoptosis - drug effects</subject><subject>Biochemistry & Molecular Biology</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Breast Neoplasms - therapy</subject><subject>Cancer</subject><subject>CD73</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - drug effects</subject><subject>Cell Proliferation - drug effects</subject><subject>Chemistry</subject><subject>Chemistry, Applied</subject><subject>Chitosan - analogs & derivatives</subject><subject>Chitosan - chemistry</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - metabolism</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Colorectal Neoplasms - therapy</subject><subject>Doxorubicin</subject><subject>Doxorubicin - chemistry</subject><subject>Doxorubicin - pharmacology</subject><subject>Doxorubicin - toxicity</subject><subject>Drug Compounding</subject><subject>Female</subject><subject>GPI-Linked Proteins - genetics</subject><subject>GPI-Linked Proteins - metabolism</subject><subject>Hyaluronic Acid - chemistry</subject><subject>Life Sciences & Biomedicine</subject><subject>Medicin och hälsovetenskap</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Nanoparicle</subject><subject>Nanoparticles</subject><subject>Nanotechnology</subject><subject>Neoplasm Invasiveness</subject><subject>Neovascularization, Pathologic</subject><subject>Physical Sciences</subject><subject>Polymer Science</subject><subject>RNA, Small Interfering - chemistry</subject><subject>RNA, Small Interfering - genetics</subject><subject>RNA, Small Interfering - metabolism</subject><subject>RNAi Therapeutics</subject><subject>Science & Technology</subject><subject>siRNA</subject><subject>tat Gene Products, Human Immunodeficiency Virus - chemistry</subject><issn>0141-8130</issn><issn>1879-0003</issn><issn>1879-0003</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>HGBXW</sourceid><sourceid>EIF</sourceid><recordid>eNqNks2O0zAURiMEYsrAK4y8Rym247_uKB0YkEYgobK2HMeh7qRxZTvtlFfj5eZWacsKQTaO7z3nRvHnorgheEowEe_WU7-ufdgYO6WYkimWU1yxZ8WEKDkrMcbV82KCCSOlIhW-Kl6ltIaq4ES9LK4qRhmXlZwUvz90wT6YxqHQosWtrNCQfP8TJf_96xx1AToNsiufQzI96ozNJjvUmz5sTczedi6hduht9qE3nf8F9N7nFVrOl-XqYLohQh0M169MbwFuwmOIQ-2t79HGNR6a8IFDDjk8QjEfEDTskY3Iuq5LqA4wD4o7n2NApm_GzS68Ll60pkvuzWm9Ln58-rhcfC7vv919WczvS8u4yKWoWuVmhIhWEcMrxYUlDW2pUK0xoqGMOllTwTmvqaxbrsSMSiobalhdSWqr66Ic56a92w613ka_MfGgg_H6VHqAN6eZwFzNgJ_9ld_G0PyRziJhklGOGQFXjK6NIaXo2otNsD4mr9f6nLw-Jq-x1JA8iDejCJPhXC_aOWoA1AjsXR3aZL2DM75gx7uhFBMUHx-y8JAzRLoIQ59Bffv_KtDvR9pBJjvvoj4ZjY_OZt0E_6-feQKHR-jT</recordid><startdate>20210901</startdate><enddate>20210901</enddate><creator>Salehi Khesht, Armin Mahmoud</creator><creator>Karpisheh, Vahid</creator><creator>Sahami Gilan, Parisa</creator><creator>Melnikova, Lyubov A.</creator><creator>Olegovna Zekiy, Angelina</creator><creator>Mohammadi, Mahdis</creator><creator>Hojjat-Farsangi, Mohammad</creator><creator>Majidi Zolbanin, Naime</creator><creator>Mahmoodpoor, Ata</creator><creator>Hassannia, Hadi</creator><creator>Aghebati-Maleki, Leili</creator><creator>Jafari, Reza</creator><creator>Jadidi-Niaragh, Farhad</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>BLEPL</scope><scope>DTL</scope><scope>HGBXW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ADTPV</scope><scope>AOWAS</scope></search><sort><creationdate>20210901</creationdate><title>Blockade of CD73 using siRNA loaded chitosan lactate nanoparticles functionalized with TAT-hyaluronate enhances doxorubicin mediated cytotoxicity in cancer cells both in vitro and in vivo</title><author>Salehi Khesht, Armin Mahmoud ; Karpisheh, Vahid ; Sahami Gilan, Parisa ; Melnikova, Lyubov A. ; Olegovna Zekiy, Angelina ; Mohammadi, Mahdis ; Hojjat-Farsangi, Mohammad ; Majidi Zolbanin, Naime ; Mahmoodpoor, Ata ; Hassannia, Hadi ; Aghebati-Maleki, Leili ; Jafari, Reza ; Jadidi-Niaragh, Farhad</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c456t-63f8e9116f81a53856c1d2f268faa6d242e7b26555b27bf58692727d2a4b372c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>5'-Nucleotidase - 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Targeted delivery of these drugs to the tumor site and sensitization of cancer cells to death induced by chemotherapy drugs are ways that can overcome the limitations of the use of these drugs. In this study, we designed and generated a novel nanocarrier composed of chitosan lactate nanoparticles (NPs) functionalized by HIV-1 derived TAT peptide (Transactivating transcriptional activator) and hyaluronate (HA) to deliver CD73 siRNA and doxorubicin to 4T1 and CT26 cancer cells, both in vivo and in vitro, as a novel combinatorial treatment strategy. The CD73 molecule plays a key role in many cancer cell behaviors such as proliferation, angiogenesis, metastasis, imunosuppression, and resistance to chemotherapy. Therefore, we decided to reduce the side effects of DOX by simultaneously transmitting CD73 siRNA and DOX by CL-TAT-HA NPs, increase the susceptibility of cancer cells to DOX-induced cell death, and stimulate anti-tumor immune responses, for the first time. These results indicated that simultaneous transfer of CD73 siRNA and DOX to cancer cells (4 T1 and CT26) increased cell death and inhibited the prolifration and spread of cancer cells. Also, the preferential aggregation of NPs in the tumor microenvironment reduced tumor growh, promoted the survival of tumor-bearing mice, and induced anti-tumor immune responses. These findings indicate that CL-TAT-HA NPs are a good candidate for targeted siRNA/drug delivery to cancer cells and the simultaneous transfer of CD73 siRNA and DOX to cancer cells using this nanocarrier can be used to treat cancer.</abstract><cop>AMSTERDAM</cop><pub>Elsevier B.V</pub><pmid>34245737</pmid><doi>10.1016/j.ijbiomac.2021.07.034</doi><tpages>15</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0141-8130 |
| ispartof | International journal of biological macromolecules, 2021-09, Vol.186, p.849-863 |
| issn | 0141-8130 1879-0003 1879-0003 |
| language | eng |
| recordid | cdi_webofscience_primary_000688462000001CitationCount |
| source | MEDLINE; Web of Science - Science Citation Index Expanded - 2021<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" />; Access via ScienceDirect (Elsevier) |
| subjects | 5'-Nucleotidase - genetics 5'-Nucleotidase - metabolism Animals Antibiotics, Antineoplastic - chemistry Antibiotics, Antineoplastic - pharmacology Antibiotics, Antineoplastic - toxicity Apoptosis - drug effects Biochemistry & Molecular Biology Breast Neoplasms - genetics Breast Neoplasms - metabolism Breast Neoplasms - pathology Breast Neoplasms - therapy Cancer CD73 Cell Line, Tumor Cell Movement - drug effects Cell Proliferation - drug effects Chemistry Chemistry, Applied Chitosan - analogs & derivatives Chitosan - chemistry Colorectal Neoplasms - genetics Colorectal Neoplasms - metabolism Colorectal Neoplasms - pathology Colorectal Neoplasms - therapy Doxorubicin Doxorubicin - chemistry Doxorubicin - pharmacology Doxorubicin - toxicity Drug Compounding Female GPI-Linked Proteins - genetics GPI-Linked Proteins - metabolism Hyaluronic Acid - chemistry Life Sciences & Biomedicine Medicin och hälsovetenskap Mice Mice, Inbred BALB C Nanoparicle Nanoparticles Nanotechnology Neoplasm Invasiveness Neovascularization, Pathologic Physical Sciences Polymer Science RNA, Small Interfering - chemistry RNA, Small Interfering - genetics RNA, Small Interfering - metabolism RNAi Therapeutics Science & Technology siRNA tat Gene Products, Human Immunodeficiency Virus - chemistry |
| title | Blockade of CD73 using siRNA loaded chitosan lactate nanoparticles functionalized with TAT-hyaluronate enhances doxorubicin mediated cytotoxicity in cancer cells both in vitro and in vivo |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-11T12%3A02%3A34IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed_webof&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Blockade%20of%20CD73%20using%20siRNA%20loaded%20chitosan%20lactate%20nanoparticles%20functionalized%20with%20TAT-hyaluronate%20enhances%20doxorubicin%20mediated%20cytotoxicity%20in%20cancer%20cells%20both%20in%20vitro%20and%20in%20vivo&rft.jtitle=International%20journal%20of%20biological%20macromolecules&rft.au=Salehi%20Khesht,%20Armin%20Mahmoud&rft.date=2021-09-01&rft.volume=186&rft.spage=849&rft.epage=863&rft.pages=849-863&rft.issn=0141-8130&rft.eissn=1879-0003&rft_id=info:doi/10.1016/j.ijbiomac.2021.07.034&rft_dat=%3Cpubmed_webof%3E34245737%3C/pubmed_webof%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/34245737&rft_els_id=S0141813021014707&rfr_iscdi=true |