A Macromolecular Drug for Cancer Therapy via Extracellular Calcification
Cancer chemotherapy typically relies on drug endocytosis and inhibits tumor cell proliferation via intracellular pathways; however, severe side effects may arise. In this study, we performed a first attempt to develop macromolecular‐induced extracellular chemotherapy involving biomineralization by a...
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Veröffentlicht in: | Angewandte Chemie 2021-03, Vol.133 (12), p.6583-6591 |
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creator | Tang, Ning Li, Hanhui Zhang, Lihong Zhang, Xueyun Chen, Yanni Shou, Hao Feng, Shuaishuai Chen, Xinhua Luo, Yan Tang, Ruikang Wang, Ben |
description | Cancer chemotherapy typically relies on drug endocytosis and inhibits tumor cell proliferation via intracellular pathways; however, severe side effects may arise. In this study, we performed a first attempt to develop macromolecular‐induced extracellular chemotherapy involving biomineralization by absorbing calcium from the blood through a new type of drug, polysialic acid conjugated with folate (folate‐polySia), which selectively induces biogenic mineral formation on tumor cells and results in the pathological calcification of tumors. The macromolecule‐initiated extracellular calcification causes cancer cell death mainly by intervening with the glycolysis process in cancer cells. Systemic administration of folate‐polySia inhibited cervical and breast tumor growth and dramatically improved survival rates in mice. This study provides an extracellular therapeutic approach for malignant tumor diseases via calcification that is ready for clinical trials and offers new insights into macromolecular anticancer drug discovery.
We propose a macromolecular‐drug‐induced extracellular chemotherapy involving biomineralization by absorbing calcium from blood. Polysialic acid combined with folate, which spontaneously induces biogenic mineral formation on cancer cells rich in folate receptors, leads to targeted pathological calcification and cell death. Systemic administration of folate‐polySia improves survival rates of tumor‐bearing mice with negligible side effects. |
doi_str_mv | 10.1002/ange.202016122 |
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We propose a macromolecular‐drug‐induced extracellular chemotherapy involving biomineralization by absorbing calcium from blood. Polysialic acid combined with folate, which spontaneously induces biogenic mineral formation on cancer cells rich in folate receptors, leads to targeted pathological calcification and cell death. Systemic administration of folate‐polySia improves survival rates of tumor‐bearing mice with negligible side effects.</description><identifier>ISSN: 0044-8249</identifier><identifier>EISSN: 1521-3757</identifier><identifier>DOI: 10.1002/ange.202016122</identifier><language>eng</language><publisher>Weinheim: Wiley Subscription Services, Inc</publisher><subject>antitumor therapy ; biomineralization ; Breast cancer ; Calcification ; Calcium ; Calcium (blood) ; Cancer ; Cancer therapies ; Cell death ; Cell proliferation ; Cervix ; Chemistry ; Chemotherapy ; Clinical trials ; Endocytosis ; Folic acid ; Glycolysis ; macromolecular drug ; Macromolecules ; Mineralization ; Polysialic acid ; Side effects ; Survival ; Tumor cells ; Tumors ; Vitamin B</subject><ispartof>Angewandte Chemie, 2021-03, Vol.133 (12), p.6583-6591</ispartof><rights>2021 Wiley‐VCH GmbH</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1622-bae6a07e35ca9d9fbbc34afd9963eafffee5f8178f06ca58c4c707c38525125b3</citedby><cites>FETCH-LOGICAL-c1622-bae6a07e35ca9d9fbbc34afd9963eafffee5f8178f06ca58c4c707c38525125b3</cites><orcidid>0000-0001-5277-7338 ; 0000-0002-4134-1835</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fange.202016122$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fange.202016122$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids></links><search><creatorcontrib>Tang, Ning</creatorcontrib><creatorcontrib>Li, Hanhui</creatorcontrib><creatorcontrib>Zhang, Lihong</creatorcontrib><creatorcontrib>Zhang, Xueyun</creatorcontrib><creatorcontrib>Chen, Yanni</creatorcontrib><creatorcontrib>Shou, Hao</creatorcontrib><creatorcontrib>Feng, Shuaishuai</creatorcontrib><creatorcontrib>Chen, Xinhua</creatorcontrib><creatorcontrib>Luo, Yan</creatorcontrib><creatorcontrib>Tang, Ruikang</creatorcontrib><creatorcontrib>Wang, Ben</creatorcontrib><title>A Macromolecular Drug for Cancer Therapy via Extracellular Calcification</title><title>Angewandte Chemie</title><description>Cancer chemotherapy typically relies on drug endocytosis and inhibits tumor cell proliferation via intracellular pathways; however, severe side effects may arise. In this study, we performed a first attempt to develop macromolecular‐induced extracellular chemotherapy involving biomineralization by absorbing calcium from the blood through a new type of drug, polysialic acid conjugated with folate (folate‐polySia), which selectively induces biogenic mineral formation on tumor cells and results in the pathological calcification of tumors. The macromolecule‐initiated extracellular calcification causes cancer cell death mainly by intervening with the glycolysis process in cancer cells. Systemic administration of folate‐polySia inhibited cervical and breast tumor growth and dramatically improved survival rates in mice. This study provides an extracellular therapeutic approach for malignant tumor diseases via calcification that is ready for clinical trials and offers new insights into macromolecular anticancer drug discovery.
We propose a macromolecular‐drug‐induced extracellular chemotherapy involving biomineralization by absorbing calcium from blood. Polysialic acid combined with folate, which spontaneously induces biogenic mineral formation on cancer cells rich in folate receptors, leads to targeted pathological calcification and cell death. Systemic administration of folate‐polySia improves survival rates of tumor‐bearing mice with negligible side effects.</description><subject>antitumor therapy</subject><subject>biomineralization</subject><subject>Breast cancer</subject><subject>Calcification</subject><subject>Calcium</subject><subject>Calcium (blood)</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Cell death</subject><subject>Cell proliferation</subject><subject>Cervix</subject><subject>Chemistry</subject><subject>Chemotherapy</subject><subject>Clinical trials</subject><subject>Endocytosis</subject><subject>Folic acid</subject><subject>Glycolysis</subject><subject>macromolecular drug</subject><subject>Macromolecules</subject><subject>Mineralization</subject><subject>Polysialic acid</subject><subject>Side effects</subject><subject>Survival</subject><subject>Tumor cells</subject><subject>Tumors</subject><subject>Vitamin B</subject><issn>0044-8249</issn><issn>1521-3757</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNqFkDFPwzAQhS0EEqWwMkdiTjk7dmyPVSgtUoGlzNbFtUsqNylOA_Tfk1IEI9Mt33un9xFyTWFEAdgt1is3YsCA5pSxEzKggtE0k0KekgEA56liXJ-Ti7ZdA0DOpB6Q2Th5RBubTROc7QLG5C52q8Q3MSmwti4mi1cXcbtP3itMJp-7iNaF8E0WGGzlK4u7qqkvyZnH0LqrnzskL_eTRTFL58_Th2I8Ty3NGUtLdDmCdJmwqJfal6XNOPql1nnm0HvvnPCKSuUhtyiU5VaCtJkSTFAmymxIbo6929i8da7dmXXTxbp_afp1UnPJleqp0ZHqp7VtdN5sY7XBuDcUzMGWOdgyv7b6gD4GPqrg9v_QZvw0nfxlvwC91G6e</recordid><startdate>20210315</startdate><enddate>20210315</enddate><creator>Tang, Ning</creator><creator>Li, Hanhui</creator><creator>Zhang, Lihong</creator><creator>Zhang, Xueyun</creator><creator>Chen, Yanni</creator><creator>Shou, Hao</creator><creator>Feng, Shuaishuai</creator><creator>Chen, Xinhua</creator><creator>Luo, Yan</creator><creator>Tang, Ruikang</creator><creator>Wang, Ben</creator><general>Wiley Subscription Services, Inc</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>L7M</scope><orcidid>https://orcid.org/0000-0001-5277-7338</orcidid><orcidid>https://orcid.org/0000-0002-4134-1835</orcidid></search><sort><creationdate>20210315</creationdate><title>A Macromolecular Drug for Cancer Therapy via Extracellular Calcification</title><author>Tang, Ning ; Li, Hanhui ; Zhang, Lihong ; Zhang, Xueyun ; Chen, Yanni ; Shou, Hao ; Feng, Shuaishuai ; Chen, Xinhua ; Luo, Yan ; Tang, Ruikang ; Wang, Ben</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1622-bae6a07e35ca9d9fbbc34afd9963eafffee5f8178f06ca58c4c707c38525125b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>antitumor therapy</topic><topic>biomineralization</topic><topic>Breast cancer</topic><topic>Calcification</topic><topic>Calcium</topic><topic>Calcium (blood)</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Cell death</topic><topic>Cell proliferation</topic><topic>Cervix</topic><topic>Chemistry</topic><topic>Chemotherapy</topic><topic>Clinical trials</topic><topic>Endocytosis</topic><topic>Folic acid</topic><topic>Glycolysis</topic><topic>macromolecular drug</topic><topic>Macromolecules</topic><topic>Mineralization</topic><topic>Polysialic acid</topic><topic>Side effects</topic><topic>Survival</topic><topic>Tumor cells</topic><topic>Tumors</topic><topic>Vitamin B</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tang, Ning</creatorcontrib><creatorcontrib>Li, Hanhui</creatorcontrib><creatorcontrib>Zhang, Lihong</creatorcontrib><creatorcontrib>Zhang, Xueyun</creatorcontrib><creatorcontrib>Chen, Yanni</creatorcontrib><creatorcontrib>Shou, Hao</creatorcontrib><creatorcontrib>Feng, Shuaishuai</creatorcontrib><creatorcontrib>Chen, Xinhua</creatorcontrib><creatorcontrib>Luo, Yan</creatorcontrib><creatorcontrib>Tang, Ruikang</creatorcontrib><creatorcontrib>Wang, Ben</creatorcontrib><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><jtitle>Angewandte Chemie</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tang, Ning</au><au>Li, Hanhui</au><au>Zhang, Lihong</au><au>Zhang, Xueyun</au><au>Chen, Yanni</au><au>Shou, Hao</au><au>Feng, Shuaishuai</au><au>Chen, Xinhua</au><au>Luo, Yan</au><au>Tang, Ruikang</au><au>Wang, Ben</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Macromolecular Drug for Cancer Therapy via Extracellular Calcification</atitle><jtitle>Angewandte Chemie</jtitle><date>2021-03-15</date><risdate>2021</risdate><volume>133</volume><issue>12</issue><spage>6583</spage><epage>6591</epage><pages>6583-6591</pages><issn>0044-8249</issn><eissn>1521-3757</eissn><abstract>Cancer chemotherapy typically relies on drug endocytosis and inhibits tumor cell proliferation via intracellular pathways; however, severe side effects may arise. In this study, we performed a first attempt to develop macromolecular‐induced extracellular chemotherapy involving biomineralization by absorbing calcium from the blood through a new type of drug, polysialic acid conjugated with folate (folate‐polySia), which selectively induces biogenic mineral formation on tumor cells and results in the pathological calcification of tumors. The macromolecule‐initiated extracellular calcification causes cancer cell death mainly by intervening with the glycolysis process in cancer cells. Systemic administration of folate‐polySia inhibited cervical and breast tumor growth and dramatically improved survival rates in mice. This study provides an extracellular therapeutic approach for malignant tumor diseases via calcification that is ready for clinical trials and offers new insights into macromolecular anticancer drug discovery.
We propose a macromolecular‐drug‐induced extracellular chemotherapy involving biomineralization by absorbing calcium from blood. Polysialic acid combined with folate, which spontaneously induces biogenic mineral formation on cancer cells rich in folate receptors, leads to targeted pathological calcification and cell death. Systemic administration of folate‐polySia improves survival rates of tumor‐bearing mice with negligible side effects.</abstract><cop>Weinheim</cop><pub>Wiley Subscription Services, Inc</pub><doi>10.1002/ange.202016122</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-5277-7338</orcidid><orcidid>https://orcid.org/0000-0002-4134-1835</orcidid></addata></record> |
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subjects | antitumor therapy biomineralization Breast cancer Calcification Calcium Calcium (blood) Cancer Cancer therapies Cell death Cell proliferation Cervix Chemistry Chemotherapy Clinical trials Endocytosis Folic acid Glycolysis macromolecular drug Macromolecules Mineralization Polysialic acid Side effects Survival Tumor cells Tumors Vitamin B |
title | A Macromolecular Drug for Cancer Therapy via Extracellular Calcification |
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