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Synergistic action of lactoferrin in enhancing the safety and effectiveness of docetaxel treatment against prostate cancer
Background Tumor metastasis is promoted by an immunosuppressive environment. Lactoferrin (Lf) is known to regulate immunological activity in tumor cells and inhibit processes associated with tumor metastasis. A delivery of lactoferrin with docetaxel (DTX) in prostate cancer cells in the form of DTX-...
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| Published in: | Cancer chemotherapy and pharmacology 2023-05, Vol.91 (5), p.375-387 |
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| container_title | Cancer chemotherapy and pharmacology |
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| creator | Muj, Chukhu Mukhopadhyay, Satyajit Jana, Pritikana Kondapi, Anand K. |
| description | Background
Tumor metastasis is promoted by an immunosuppressive environment. Lactoferrin (Lf) is known to regulate immunological activity in tumor cells and inhibit processes associated with tumor metastasis. A delivery of lactoferrin with docetaxel (DTX) in prostate cancer cells in
the form of DTX-loaded lactoferrin nanoparticles (DTX-LfNPs) would provide a dual activity wherein the lactoferrin affects metastasis and DTX chemotherapeutically inhibits mitosis and cell division.
Methods
DTX-LfNPs were prepared using sol–oil chemistry, and particles were characterized using transmission electron microscopy. Antiproliferation activity was analyzed in prostate cancer Mat Ly Lu cells. The target localization and efficacy of DTX-LfNPs were studied in an orthotopic prostate cancer induced by Mat Ly Lu cells in a rat model. Biomarkers were estimated using ELISA and biochemical reactions.
Results
DTX was loaded in pure Lf nanoparticles without involving any chemical modification and conjugation, thus when these nanoparticles are delivered in cancer cells both DTX and Lf will be present in biologically active forms. DTX-LfNps exhibit a spherical morphology of dimension of 60 ± 10 nm with DTX Encapsulation Efficiency of 62.06 ± 4.07%. Competition experiments using soluble Lf confirm that DTX-LfNPs enter prostate cancer cells through the Lf receptor. DTX-LfNPs exhibit an improved anti-proliferative activity by 2.5 times compared to DTX. Further, analysis of the bioavailability of the drug in the prostate showed that DTX-LfNPs increased drug bioavailability in the prostate by two times more than the DTX. The analysis of efficacy in the Mat Ly Lu cells-induced orthotopic prostate cancer model showed that DTX-LfNPs significantly enhanced the anti-cancer activity compared to DTX in terms of regression of weight and volume of prostate tissue, the efficacy was confirmed by histochemical analysis. Lf provides synergistic activity along with DTX in inhibiting metastasis as assessed by the reduction of lactate dehydrogenase, alkaline phosphatase, TNF alpha, and IFNγ. LfNPs facilitate higher DTX localization along with Lf-mediated protection from DTX-associated toxicity to neutrophils and kidneys as assessed by C-reactive protein, creatinine, and uric acid. Thus, DTX LfNPs show a dual action by enhancing DTX bioavailability in prostate along with Lf-mediated suppression of metastasis as well as DTX-associated toxicity.
Conclusion
In conclusion, DTX-LfNPs enhance the bioavailabi |
| doi_str_mv | 10.1007/s00280-023-04524-9 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2792512156</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2808755309</sourcerecordid><originalsourceid>FETCH-LOGICAL-c375t-acd5578cdac69c810d1fb46f09147274ed9e027ce025706036586edcde50713a3</originalsourceid><addsrcrecordid>eNp9kV9PHCEUxYlpo-vWL-CDIemLL2Mv_4aZR2NaNTHpQ9tngnDZnc0sY4E1rp--rKs16UMJARJ-51wuh5BTBhcMQH_JALyDBrhoQCoum_6AzJgUvIFOig9kBkLKRmmQR-Q45xUASCbEITkSba_rYDPy_GMbMS2GXAZHrSvDFOkU6FiPU8CUhkjrxLi00Q1xQcsSabYBy5ba6CmGgFX0iBFz3gn95LDYJxxpSWjLGmOhdmGHmAt9SFMutiB11QzTJ_Ix2DHjyes-J7--ff15ddPcfb--vbq8a5zQqjTWeaV057x1be86Bp6Fe9kG6JnUXEv0PQLXri611RZEq7oWvfOoQDNhxZyc731r_d8bzMWsh-xwHG3EaZMN1z1XjDPVVvTzP-hq2qRYX2fqT3daKQF9pfiecrWhnDCYhzSsbdoaBmaXjNknY2oy5iUZsxOdvVpv7tfo_0reoqiA2AO5XsUFpvfa_7H9A6nvmpY</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2808755309</pqid></control><display><type>article</type><title>Synergistic action of lactoferrin in enhancing the safety and effectiveness of docetaxel treatment against prostate cancer</title><source>Springer Link</source><creator>Muj, Chukhu ; Mukhopadhyay, Satyajit ; Jana, Pritikana ; Kondapi, Anand K.</creator><creatorcontrib>Muj, Chukhu ; Mukhopadhyay, Satyajit ; Jana, Pritikana ; Kondapi, Anand K.</creatorcontrib><description>Background
Tumor metastasis is promoted by an immunosuppressive environment. Lactoferrin (Lf) is known to regulate immunological activity in tumor cells and inhibit processes associated with tumor metastasis. A delivery of lactoferrin with docetaxel (DTX) in prostate cancer cells in
the form of DTX-loaded lactoferrin nanoparticles (DTX-LfNPs) would provide a dual activity wherein the lactoferrin affects metastasis and DTX chemotherapeutically inhibits mitosis and cell division.
Methods
DTX-LfNPs were prepared using sol–oil chemistry, and particles were characterized using transmission electron microscopy. Antiproliferation activity was analyzed in prostate cancer Mat Ly Lu cells. The target localization and efficacy of DTX-LfNPs were studied in an orthotopic prostate cancer induced by Mat Ly Lu cells in a rat model. Biomarkers were estimated using ELISA and biochemical reactions.
Results
DTX was loaded in pure Lf nanoparticles without involving any chemical modification and conjugation, thus when these nanoparticles are delivered in cancer cells both DTX and Lf will be present in biologically active forms. DTX-LfNps exhibit a spherical morphology of dimension of 60 ± 10 nm with DTX Encapsulation Efficiency of 62.06 ± 4.07%. Competition experiments using soluble Lf confirm that DTX-LfNPs enter prostate cancer cells through the Lf receptor. DTX-LfNPs exhibit an improved anti-proliferative activity by 2.5 times compared to DTX. Further, analysis of the bioavailability of the drug in the prostate showed that DTX-LfNPs increased drug bioavailability in the prostate by two times more than the DTX. The analysis of efficacy in the Mat Ly Lu cells-induced orthotopic prostate cancer model showed that DTX-LfNPs significantly enhanced the anti-cancer activity compared to DTX in terms of regression of weight and volume of prostate tissue, the efficacy was confirmed by histochemical analysis. Lf provides synergistic activity along with DTX in inhibiting metastasis as assessed by the reduction of lactate dehydrogenase, alkaline phosphatase, TNF alpha, and IFNγ. LfNPs facilitate higher DTX localization along with Lf-mediated protection from DTX-associated toxicity to neutrophils and kidneys as assessed by C-reactive protein, creatinine, and uric acid. Thus, DTX LfNPs show a dual action by enhancing DTX bioavailability in prostate along with Lf-mediated suppression of metastasis as well as DTX-associated toxicity.
Conclusion
In conclusion, DTX-LfNPs enhance the bioavailability of DTX in the prostate along with Lf-assisted improvement in inhibition of tumor metastasis and drug-associated toxicity.</description><identifier>ISSN: 0344-5704</identifier><identifier>EISSN: 1432-0843</identifier><identifier>DOI: 10.1007/s00280-023-04524-9</identifier><identifier>PMID: 36977771</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Alkaline phosphatase ; Animals ; Anticancer properties ; Antineoplastic Agents - adverse effects ; Antineoplastic Agents - chemistry ; Antitumor activity ; Bioavailability ; Biological activity ; Biomarkers ; C-reactive protein ; Cancer Research ; Cell division ; Cell Line, Tumor ; Chemical modification ; Chemotherapy ; Conjugation ; Creatinine ; Docetaxel ; Drug Carriers - chemistry ; Effectiveness ; Enzyme-linked immunosorbent assay ; Histochemical analysis ; Humans ; Immunology ; Inhibitor drugs ; Interferon ; Kidneys ; L-Lactate dehydrogenase ; Lactate dehydrogenase ; Lactoferrin ; Lactoferrin - chemistry ; Lactoferrin - metabolism ; Lactoferrin - pharmacology ; Leukocytes ; Leukocytes (neutrophilic) ; Localization ; Male ; Medicine ; Medicine & Public Health ; Metastases ; Metastasis ; Mitosis ; Nanoparticles ; Nanoparticles - chemistry ; Oncology ; Original Article ; Pharmacology/Toxicology ; Prostate cancer ; Prostatic Neoplasms - drug therapy ; Rats ; Toxicity ; Transmission electron microscopy ; Tumor cells ; Tumors ; Uric acid ; γ-Interferon</subject><ispartof>Cancer chemotherapy and pharmacology, 2023-05, Vol.91 (5), p.375-387</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-acd5578cdac69c810d1fb46f09147274ed9e027ce025706036586edcde50713a3</citedby><cites>FETCH-LOGICAL-c375t-acd5578cdac69c810d1fb46f09147274ed9e027ce025706036586edcde50713a3</cites><orcidid>0000-0002-0711-3126</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36977771$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Muj, Chukhu</creatorcontrib><creatorcontrib>Mukhopadhyay, Satyajit</creatorcontrib><creatorcontrib>Jana, Pritikana</creatorcontrib><creatorcontrib>Kondapi, Anand K.</creatorcontrib><title>Synergistic action of lactoferrin in enhancing the safety and effectiveness of docetaxel treatment against prostate cancer</title><title>Cancer chemotherapy and pharmacology</title><addtitle>Cancer Chemother Pharmacol</addtitle><addtitle>Cancer Chemother Pharmacol</addtitle><description>Background
Tumor metastasis is promoted by an immunosuppressive environment. Lactoferrin (Lf) is known to regulate immunological activity in tumor cells and inhibit processes associated with tumor metastasis. A delivery of lactoferrin with docetaxel (DTX) in prostate cancer cells in
the form of DTX-loaded lactoferrin nanoparticles (DTX-LfNPs) would provide a dual activity wherein the lactoferrin affects metastasis and DTX chemotherapeutically inhibits mitosis and cell division.
Methods
DTX-LfNPs were prepared using sol–oil chemistry, and particles were characterized using transmission electron microscopy. Antiproliferation activity was analyzed in prostate cancer Mat Ly Lu cells. The target localization and efficacy of DTX-LfNPs were studied in an orthotopic prostate cancer induced by Mat Ly Lu cells in a rat model. Biomarkers were estimated using ELISA and biochemical reactions.
Results
DTX was loaded in pure Lf nanoparticles without involving any chemical modification and conjugation, thus when these nanoparticles are delivered in cancer cells both DTX and Lf will be present in biologically active forms. DTX-LfNps exhibit a spherical morphology of dimension of 60 ± 10 nm with DTX Encapsulation Efficiency of 62.06 ± 4.07%. Competition experiments using soluble Lf confirm that DTX-LfNPs enter prostate cancer cells through the Lf receptor. DTX-LfNPs exhibit an improved anti-proliferative activity by 2.5 times compared to DTX. Further, analysis of the bioavailability of the drug in the prostate showed that DTX-LfNPs increased drug bioavailability in the prostate by two times more than the DTX. The analysis of efficacy in the Mat Ly Lu cells-induced orthotopic prostate cancer model showed that DTX-LfNPs significantly enhanced the anti-cancer activity compared to DTX in terms of regression of weight and volume of prostate tissue, the efficacy was confirmed by histochemical analysis. Lf provides synergistic activity along with DTX in inhibiting metastasis as assessed by the reduction of lactate dehydrogenase, alkaline phosphatase, TNF alpha, and IFNγ. LfNPs facilitate higher DTX localization along with Lf-mediated protection from DTX-associated toxicity to neutrophils and kidneys as assessed by C-reactive protein, creatinine, and uric acid. Thus, DTX LfNPs show a dual action by enhancing DTX bioavailability in prostate along with Lf-mediated suppression of metastasis as well as DTX-associated toxicity.
Conclusion
In conclusion, DTX-LfNPs enhance the bioavailability of DTX in the prostate along with Lf-assisted improvement in inhibition of tumor metastasis and drug-associated toxicity.</description><subject>Alkaline phosphatase</subject><subject>Animals</subject><subject>Anticancer properties</subject><subject>Antineoplastic Agents - adverse effects</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antitumor activity</subject><subject>Bioavailability</subject><subject>Biological activity</subject><subject>Biomarkers</subject><subject>C-reactive protein</subject><subject>Cancer Research</subject><subject>Cell division</subject><subject>Cell Line, Tumor</subject><subject>Chemical modification</subject><subject>Chemotherapy</subject><subject>Conjugation</subject><subject>Creatinine</subject><subject>Docetaxel</subject><subject>Drug Carriers - chemistry</subject><subject>Effectiveness</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Histochemical analysis</subject><subject>Humans</subject><subject>Immunology</subject><subject>Inhibitor drugs</subject><subject>Interferon</subject><subject>Kidneys</subject><subject>L-Lactate dehydrogenase</subject><subject>Lactate dehydrogenase</subject><subject>Lactoferrin</subject><subject>Lactoferrin - chemistry</subject><subject>Lactoferrin - metabolism</subject><subject>Lactoferrin - pharmacology</subject><subject>Leukocytes</subject><subject>Leukocytes (neutrophilic)</subject><subject>Localization</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mitosis</subject><subject>Nanoparticles</subject><subject>Nanoparticles - chemistry</subject><subject>Oncology</subject><subject>Original Article</subject><subject>Pharmacology/Toxicology</subject><subject>Prostate cancer</subject><subject>Prostatic Neoplasms - drug therapy</subject><subject>Rats</subject><subject>Toxicity</subject><subject>Transmission electron microscopy</subject><subject>Tumor cells</subject><subject>Tumors</subject><subject>Uric acid</subject><subject>γ-Interferon</subject><issn>0344-5704</issn><issn>1432-0843</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9kV9PHCEUxYlpo-vWL-CDIemLL2Mv_4aZR2NaNTHpQ9tngnDZnc0sY4E1rp--rKs16UMJARJ-51wuh5BTBhcMQH_JALyDBrhoQCoum_6AzJgUvIFOig9kBkLKRmmQR-Q45xUASCbEITkSba_rYDPy_GMbMS2GXAZHrSvDFOkU6FiPU8CUhkjrxLi00Q1xQcsSabYBy5ba6CmGgFX0iBFz3gn95LDYJxxpSWjLGmOhdmGHmAt9SFMutiB11QzTJ_Ix2DHjyes-J7--ff15ddPcfb--vbq8a5zQqjTWeaV057x1be86Bp6Fe9kG6JnUXEv0PQLXri611RZEq7oWvfOoQDNhxZyc731r_d8bzMWsh-xwHG3EaZMN1z1XjDPVVvTzP-hq2qRYX2fqT3daKQF9pfiecrWhnDCYhzSsbdoaBmaXjNknY2oy5iUZsxOdvVpv7tfo_0reoqiA2AO5XsUFpvfa_7H9A6nvmpY</recordid><startdate>20230501</startdate><enddate>20230501</enddate><creator>Muj, Chukhu</creator><creator>Mukhopadhyay, Satyajit</creator><creator>Jana, Pritikana</creator><creator>Kondapi, Anand K.</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><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>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-0711-3126</orcidid></search><sort><creationdate>20230501</creationdate><title>Synergistic action of lactoferrin in enhancing the safety and effectiveness of docetaxel treatment against prostate cancer</title><author>Muj, Chukhu ; Mukhopadhyay, Satyajit ; Jana, Pritikana ; Kondapi, Anand K.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-acd5578cdac69c810d1fb46f09147274ed9e027ce025706036586edcde50713a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Alkaline phosphatase</topic><topic>Animals</topic><topic>Anticancer properties</topic><topic>Antineoplastic Agents - adverse effects</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antitumor activity</topic><topic>Bioavailability</topic><topic>Biological activity</topic><topic>Biomarkers</topic><topic>C-reactive protein</topic><topic>Cancer Research</topic><topic>Cell division</topic><topic>Cell Line, Tumor</topic><topic>Chemical modification</topic><topic>Chemotherapy</topic><topic>Conjugation</topic><topic>Creatinine</topic><topic>Docetaxel</topic><topic>Drug Carriers - chemistry</topic><topic>Effectiveness</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Histochemical analysis</topic><topic>Humans</topic><topic>Immunology</topic><topic>Inhibitor drugs</topic><topic>Interferon</topic><topic>Kidneys</topic><topic>L-Lactate dehydrogenase</topic><topic>Lactate dehydrogenase</topic><topic>Lactoferrin</topic><topic>Lactoferrin - chemistry</topic><topic>Lactoferrin - metabolism</topic><topic>Lactoferrin - pharmacology</topic><topic>Leukocytes</topic><topic>Leukocytes (neutrophilic)</topic><topic>Localization</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Mitosis</topic><topic>Nanoparticles</topic><topic>Nanoparticles - chemistry</topic><topic>Oncology</topic><topic>Original Article</topic><topic>Pharmacology/Toxicology</topic><topic>Prostate cancer</topic><topic>Prostatic Neoplasms - drug therapy</topic><topic>Rats</topic><topic>Toxicity</topic><topic>Transmission electron microscopy</topic><topic>Tumor cells</topic><topic>Tumors</topic><topic>Uric acid</topic><topic>γ-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Muj, Chukhu</creatorcontrib><creatorcontrib>Mukhopadhyay, Satyajit</creatorcontrib><creatorcontrib>Jana, Pritikana</creatorcontrib><creatorcontrib>Kondapi, Anand K.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer chemotherapy and pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Muj, Chukhu</au><au>Mukhopadhyay, Satyajit</au><au>Jana, Pritikana</au><au>Kondapi, Anand K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synergistic action of lactoferrin in enhancing the safety and effectiveness of docetaxel treatment against prostate cancer</atitle><jtitle>Cancer chemotherapy and pharmacology</jtitle><stitle>Cancer Chemother Pharmacol</stitle><addtitle>Cancer Chemother Pharmacol</addtitle><date>2023-05-01</date><risdate>2023</risdate><volume>91</volume><issue>5</issue><spage>375</spage><epage>387</epage><pages>375-387</pages><issn>0344-5704</issn><eissn>1432-0843</eissn><abstract>Background
Tumor metastasis is promoted by an immunosuppressive environment. Lactoferrin (Lf) is known to regulate immunological activity in tumor cells and inhibit processes associated with tumor metastasis. A delivery of lactoferrin with docetaxel (DTX) in prostate cancer cells in
the form of DTX-loaded lactoferrin nanoparticles (DTX-LfNPs) would provide a dual activity wherein the lactoferrin affects metastasis and DTX chemotherapeutically inhibits mitosis and cell division.
Methods
DTX-LfNPs were prepared using sol–oil chemistry, and particles were characterized using transmission electron microscopy. Antiproliferation activity was analyzed in prostate cancer Mat Ly Lu cells. The target localization and efficacy of DTX-LfNPs were studied in an orthotopic prostate cancer induced by Mat Ly Lu cells in a rat model. Biomarkers were estimated using ELISA and biochemical reactions.
Results
DTX was loaded in pure Lf nanoparticles without involving any chemical modification and conjugation, thus when these nanoparticles are delivered in cancer cells both DTX and Lf will be present in biologically active forms. DTX-LfNps exhibit a spherical morphology of dimension of 60 ± 10 nm with DTX Encapsulation Efficiency of 62.06 ± 4.07%. Competition experiments using soluble Lf confirm that DTX-LfNPs enter prostate cancer cells through the Lf receptor. DTX-LfNPs exhibit an improved anti-proliferative activity by 2.5 times compared to DTX. Further, analysis of the bioavailability of the drug in the prostate showed that DTX-LfNPs increased drug bioavailability in the prostate by two times more than the DTX. The analysis of efficacy in the Mat Ly Lu cells-induced orthotopic prostate cancer model showed that DTX-LfNPs significantly enhanced the anti-cancer activity compared to DTX in terms of regression of weight and volume of prostate tissue, the efficacy was confirmed by histochemical analysis. Lf provides synergistic activity along with DTX in inhibiting metastasis as assessed by the reduction of lactate dehydrogenase, alkaline phosphatase, TNF alpha, and IFNγ. LfNPs facilitate higher DTX localization along with Lf-mediated protection from DTX-associated toxicity to neutrophils and kidneys as assessed by C-reactive protein, creatinine, and uric acid. Thus, DTX LfNPs show a dual action by enhancing DTX bioavailability in prostate along with Lf-mediated suppression of metastasis as well as DTX-associated toxicity.
Conclusion
In conclusion, DTX-LfNPs enhance the bioavailability of DTX in the prostate along with Lf-assisted improvement in inhibition of tumor metastasis and drug-associated toxicity.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>36977771</pmid><doi>10.1007/s00280-023-04524-9</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-0711-3126</orcidid></addata></record> |
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| subjects | Alkaline phosphatase Animals Anticancer properties Antineoplastic Agents - adverse effects Antineoplastic Agents - chemistry Antitumor activity Bioavailability Biological activity Biomarkers C-reactive protein Cancer Research Cell division Cell Line, Tumor Chemical modification Chemotherapy Conjugation Creatinine Docetaxel Drug Carriers - chemistry Effectiveness Enzyme-linked immunosorbent assay Histochemical analysis Humans Immunology Inhibitor drugs Interferon Kidneys L-Lactate dehydrogenase Lactate dehydrogenase Lactoferrin Lactoferrin - chemistry Lactoferrin - metabolism Lactoferrin - pharmacology Leukocytes Leukocytes (neutrophilic) Localization Male Medicine Medicine & Public Health Metastases Metastasis Mitosis Nanoparticles Nanoparticles - chemistry Oncology Original Article Pharmacology/Toxicology Prostate cancer Prostatic Neoplasms - drug therapy Rats Toxicity Transmission electron microscopy Tumor cells Tumors Uric acid γ-Interferon |
| title | Synergistic action of lactoferrin in enhancing the safety and effectiveness of docetaxel treatment against prostate cancer |
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