Tumor-Targeted Codelivery of CpG and siRNA by a Dual-Ligand-Functionalized Curdlan Nanoparticle
The simultaneous delivery of CpG oligonucleotide along with short interfering RNA (siRNA) has the potential to significantly boost the anticancer impact of siRNA medications. Our previous research demonstrated that Curdlan nanoparticles functionalized with adenosine are capable of selectively delive...
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Veröffentlicht in: | Biomacromolecules 2024-06, Vol.25 (6), p.3360-3372 |
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creator | Bao, Qingming Bao, Mingming Xiao, Hai Ganbold, Tsogzolmaa Han, Shuqin Baigude, Huricha |
description | The simultaneous delivery of CpG oligonucleotide along with short interfering RNA (siRNA) has the potential to significantly boost the anticancer impact of siRNA medications. Our previous research demonstrated that Curdlan nanoparticles functionalized with adenosine are capable of selectively delivering therapeutic siRNA to cancerous cells through endocytosis mediated by adenosine receptors. Herein, we synthesized a dual-ligand-functionalized Curdlan polymer (denoted by CuMAN) to simultaneously target tumor cells and tumor-associated macrophages (TAMs). CuMAN nanoparticles containing CpG and siRNA demonstrated enhanced uptake by B16F10 tumor cells and bone marrow-derived macrophages, which are facilitated by AR on tumor cells and mannose receptor on macrophages. This led to increased release of pro-inflammatory cytokines in both in vitro and in vivo settings. The synergistic effect of CpG on TAMs and RNAi on tumor cells mediated by the CuMAN nanoparticle not only suppressed the tumor growth but also strongly inhibited the lung metastasis. Our findings indicate that the CuMAN nanoparticle has potential as an effective dual-targeting delivery system for nucleic acid therapeutics. |
doi_str_mv | 10.1021/acs.biomac.4c00025 |
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Our previous research demonstrated that Curdlan nanoparticles functionalized with adenosine are capable of selectively delivering therapeutic siRNA to cancerous cells through endocytosis mediated by adenosine receptors. Herein, we synthesized a dual-ligand-functionalized Curdlan polymer (denoted by CuMAN) to simultaneously target tumor cells and tumor-associated macrophages (TAMs). CuMAN nanoparticles containing CpG and siRNA demonstrated enhanced uptake by B16F10 tumor cells and bone marrow-derived macrophages, which are facilitated by AR on tumor cells and mannose receptor on macrophages. This led to increased release of pro-inflammatory cytokines in both in vitro and in vivo settings. The synergistic effect of CpG on TAMs and RNAi on tumor cells mediated by the CuMAN nanoparticle not only suppressed the tumor growth but also strongly inhibited the lung metastasis. 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Our previous research demonstrated that Curdlan nanoparticles functionalized with adenosine are capable of selectively delivering therapeutic siRNA to cancerous cells through endocytosis mediated by adenosine receptors. Herein, we synthesized a dual-ligand-functionalized Curdlan polymer (denoted by CuMAN) to simultaneously target tumor cells and tumor-associated macrophages (TAMs). CuMAN nanoparticles containing CpG and siRNA demonstrated enhanced uptake by B16F10 tumor cells and bone marrow-derived macrophages, which are facilitated by AR on tumor cells and mannose receptor on macrophages. This led to increased release of pro-inflammatory cytokines in both in vitro and in vivo settings. The synergistic effect of CpG on TAMs and RNAi on tumor cells mediated by the CuMAN nanoparticle not only suppressed the tumor growth but also strongly inhibited the lung metastasis. Our findings indicate that the CuMAN nanoparticle has potential as an effective dual-targeting delivery system for nucleic acid therapeutics.</description><subject>adenosine</subject><subject>Animals</subject><subject>beta-Glucans - chemistry</subject><subject>beta-Glucans - pharmacology</subject><subject>Cell Line, Tumor</subject><subject>curdlan</subject><subject>cytokines</subject><subject>Drug Delivery Systems - methods</subject><subject>endocytosis</subject><subject>Ligands</subject><subject>lungs</subject><subject>macrophages</subject><subject>Macrophages - drug effects</subject><subject>Macrophages - metabolism</subject><subject>mannose</subject><subject>Melanoma, Experimental - drug therapy</subject><subject>Melanoma, Experimental - pathology</subject><subject>metastasis</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>nanoparticles</subject><subject>Nanoparticles - chemistry</subject><subject>neoplasms</subject><subject>Oligodeoxyribonucleotides - administration & dosage</subject><subject>Oligodeoxyribonucleotides - chemistry</subject><subject>Oligodeoxyribonucleotides - pharmacology</subject><subject>oligonucleotides</subject><subject>polymers</subject><subject>RNA</subject><subject>RNA, Small Interfering - administration & dosage</subject><subject>RNA, Small Interfering - chemistry</subject><subject>RNA, Small Interfering - pharmacology</subject><subject>synergism</subject><subject>therapeutics</subject><subject>Tumor-Associated Macrophages - drug effects</subject><issn>1525-7797</issn><issn>1526-4602</issn><issn>1526-4602</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctOwzAQRS0E4lH4ARbISzYpfsR2skQFClIFEipra2I7yCiJi50gla8npYUlrGY0OvdqZi5C55RMKWH0CkyaVj60YKa5IYQwsYeOqWAyyyVh-9-9yJQq1RE6SeltREqei0N0xAulqJTiGOnl0IaYLSG-ut5ZPAvWNf7DxTUONZ6t5hg6i5N_frzG1RoDvhmgyRb-dRxnd0Nneh86aPznRjtE20CHH6ELK4i9N407RQc1NMmd7eoEvdzdLmf32eJp_jC7XmTAmewzZlntnKg4A6tcXdQ2Z4JCPp6Z16UyRgGUJStMYTkjMq-hgiIvaakEKzghfIIut76rGN4Hl3rd-mRcM-7jwpA0p4JLxqWi_6NEFJILpTaubIuaGFKKrtar6FuIa02J3mSgxwz0NgO9y2AUXez8h6p19lfy8_QRmG6BjfgtDHF8YPrL8QtW7JMt</recordid><startdate>20240610</startdate><enddate>20240610</enddate><creator>Bao, Qingming</creator><creator>Bao, Mingming</creator><creator>Xiao, Hai</creator><creator>Ganbold, Tsogzolmaa</creator><creator>Han, Shuqin</creator><creator>Baigude, Huricha</creator><general>American Chemical Society</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>7X8</scope><scope>7S9</scope><scope>L.6</scope><orcidid>https://orcid.org/0000-0001-5479-182X</orcidid></search><sort><creationdate>20240610</creationdate><title>Tumor-Targeted Codelivery of CpG and siRNA by a Dual-Ligand-Functionalized Curdlan Nanoparticle</title><author>Bao, Qingming ; Bao, Mingming ; Xiao, Hai ; Ganbold, Tsogzolmaa ; Han, Shuqin ; Baigude, Huricha</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a326t-2d2fee5b32ad7ef8fd4251a40214f97cc7aa9928c8d32064faba8491975283003</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>adenosine</topic><topic>Animals</topic><topic>beta-Glucans - chemistry</topic><topic>beta-Glucans - pharmacology</topic><topic>Cell Line, Tumor</topic><topic>curdlan</topic><topic>cytokines</topic><topic>Drug Delivery Systems - methods</topic><topic>endocytosis</topic><topic>Ligands</topic><topic>lungs</topic><topic>macrophages</topic><topic>Macrophages - drug effects</topic><topic>Macrophages - metabolism</topic><topic>mannose</topic><topic>Melanoma, Experimental - drug therapy</topic><topic>Melanoma, Experimental - pathology</topic><topic>metastasis</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>nanoparticles</topic><topic>Nanoparticles - chemistry</topic><topic>neoplasms</topic><topic>Oligodeoxyribonucleotides - administration & dosage</topic><topic>Oligodeoxyribonucleotides - chemistry</topic><topic>Oligodeoxyribonucleotides - pharmacology</topic><topic>oligonucleotides</topic><topic>polymers</topic><topic>RNA</topic><topic>RNA, Small Interfering - administration & dosage</topic><topic>RNA, Small Interfering - chemistry</topic><topic>RNA, Small Interfering - pharmacology</topic><topic>synergism</topic><topic>therapeutics</topic><topic>Tumor-Associated Macrophages - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bao, Qingming</creatorcontrib><creatorcontrib>Bao, Mingming</creatorcontrib><creatorcontrib>Xiao, Hai</creatorcontrib><creatorcontrib>Ganbold, Tsogzolmaa</creatorcontrib><creatorcontrib>Han, Shuqin</creatorcontrib><creatorcontrib>Baigude, Huricha</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Biomacromolecules</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bao, Qingming</au><au>Bao, Mingming</au><au>Xiao, Hai</au><au>Ganbold, Tsogzolmaa</au><au>Han, Shuqin</au><au>Baigude, Huricha</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tumor-Targeted Codelivery of CpG and siRNA by a Dual-Ligand-Functionalized Curdlan Nanoparticle</atitle><jtitle>Biomacromolecules</jtitle><addtitle>Biomacromolecules</addtitle><date>2024-06-10</date><risdate>2024</risdate><volume>25</volume><issue>6</issue><spage>3360</spage><epage>3372</epage><pages>3360-3372</pages><issn>1525-7797</issn><issn>1526-4602</issn><eissn>1526-4602</eissn><abstract>The simultaneous delivery of CpG oligonucleotide along with short interfering RNA (siRNA) has the potential to significantly boost the anticancer impact of siRNA medications. Our previous research demonstrated that Curdlan nanoparticles functionalized with adenosine are capable of selectively delivering therapeutic siRNA to cancerous cells through endocytosis mediated by adenosine receptors. Herein, we synthesized a dual-ligand-functionalized Curdlan polymer (denoted by CuMAN) to simultaneously target tumor cells and tumor-associated macrophages (TAMs). CuMAN nanoparticles containing CpG and siRNA demonstrated enhanced uptake by B16F10 tumor cells and bone marrow-derived macrophages, which are facilitated by AR on tumor cells and mannose receptor on macrophages. This led to increased release of pro-inflammatory cytokines in both in vitro and in vivo settings. The synergistic effect of CpG on TAMs and RNAi on tumor cells mediated by the CuMAN nanoparticle not only suppressed the tumor growth but also strongly inhibited the lung metastasis. 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subjects | adenosine Animals beta-Glucans - chemistry beta-Glucans - pharmacology Cell Line, Tumor curdlan cytokines Drug Delivery Systems - methods endocytosis Ligands lungs macrophages Macrophages - drug effects Macrophages - metabolism mannose Melanoma, Experimental - drug therapy Melanoma, Experimental - pathology metastasis Mice Mice, Inbred C57BL nanoparticles Nanoparticles - chemistry neoplasms Oligodeoxyribonucleotides - administration & dosage Oligodeoxyribonucleotides - chemistry Oligodeoxyribonucleotides - pharmacology oligonucleotides polymers RNA RNA, Small Interfering - administration & dosage RNA, Small Interfering - chemistry RNA, Small Interfering - pharmacology synergism therapeutics Tumor-Associated Macrophages - drug effects |
title | Tumor-Targeted Codelivery of CpG and siRNA by a Dual-Ligand-Functionalized Curdlan Nanoparticle |
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