Eliminating Intracellular MRSA via Mannosylated Lipid-Coated Calcium Phosphate Nanoparticles
Methicillin-resistant Staphylococcus aureus (MRSA) within cells proves exceptionally challenging to eradicate using conventional antimicrobials, resulting in recurring infections and heightened resistance. Herein, we reported an innovative mannosylated lipid-coated photodynamic/photothermal calcium...
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| Veröffentlicht in: | Molecular pharmaceutics 2024-11, Vol.21 (11), p.5772-5783 |
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| creator | Chen, Xiangjun Shi, Xiaoyi Liu, Xiao Zhai, Xuanxiang Li, Wenting Hong, Wei |
| description | Methicillin-resistant Staphylococcus aureus (MRSA) within cells proves exceptionally challenging to eradicate using conventional antimicrobials, resulting in recurring infections and heightened resistance. Herein, we reported an innovative mannosylated lipid-coated photodynamic/photothermal calcium phosphate nanoparticle (MAN-LCaP@ICG) for eradicating intracellular MRSA. The MAN-LCaP functioned as the vehicle for drug delivery, exhibiting preferential uptake by macrophages and facilitating the transport of ICG to intracellular pathogens. The MAN units integrated into MAN-LCaP@ICG could promote binding with MAN residuals on macrophage cells, as evidenced by cellular uptake assays using fluorescence microscopy and flow cytometry. Following its targeted accumulation, MAN-LCaP@ICG could enter into the cytoplasm and efficiently eradicate intracellular MRSA by a combination of the lysosome escape capability of CaP and the photodynamic and photothermal therapeutic effects of ICG. Furthermore, MAN-LCaP@ICG could kill MRSA more effectively than LCaP@ICG without MAN units or free ICG in a mouse peritoneal infection model. Therefore, MAN-LCaP@ICG provided a promising direction for human clinical application in combating intracellular infections. |
| doi_str_mv | 10.1021/acs.molpharmaceut.4c00779 |
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Herein, we reported an innovative mannosylated lipid-coated photodynamic/photothermal calcium phosphate nanoparticle (MAN-LCaP@ICG) for eradicating intracellular MRSA. The MAN-LCaP functioned as the vehicle for drug delivery, exhibiting preferential uptake by macrophages and facilitating the transport of ICG to intracellular pathogens. The MAN units integrated into MAN-LCaP@ICG could promote binding with MAN residuals on macrophage cells, as evidenced by cellular uptake assays using fluorescence microscopy and flow cytometry. Following its targeted accumulation, MAN-LCaP@ICG could enter into the cytoplasm and efficiently eradicate intracellular MRSA by a combination of the lysosome escape capability of CaP and the photodynamic and photothermal therapeutic effects of ICG. Furthermore, MAN-LCaP@ICG could kill MRSA more effectively than LCaP@ICG without MAN units or free ICG in a mouse peritoneal infection model. Therefore, MAN-LCaP@ICG provided a promising direction for human clinical application in combating intracellular infections.</description><identifier>ISSN: 1543-8384</identifier><identifier>ISSN: 1543-8392</identifier><identifier>EISSN: 1543-8392</identifier><identifier>DOI: 10.1021/acs.molpharmaceut.4c00779</identifier><identifier>PMID: 39368111</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Animals ; Anti-Bacterial Agents - administration & dosage ; Anti-Bacterial Agents - chemistry ; Anti-Bacterial Agents - pharmacology ; Calcium Phosphates - chemistry ; Female ; Humans ; Indocyanine Green - administration & dosage ; Indocyanine Green - chemistry ; Lipids - chemistry ; Macrophages - drug effects ; Mannose - chemistry ; Methicillin-Resistant Staphylococcus aureus - drug effects ; Mice ; Mice, Inbred BALB C ; Nanoparticles - chemistry ; Photochemotherapy - methods ; Photothermal Therapy - methods ; RAW 264.7 Cells ; Staphylococcal Infections - drug therapy</subject><ispartof>Molecular pharmaceutics, 2024-11, Vol.21 (11), p.5772-5783</ispartof><rights>2024 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-a237t-32c8c7e8788c8ad3725f16302c78f7ff881045909a7d56317997bc74b4409ea83</cites><orcidid>0000-0001-6926-8329 ; 0000-0003-1986-3044 ; 0000-0001-5591-8028</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acs.molpharmaceut.4c00779$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acs.molpharmaceut.4c00779$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2751,27055,27903,27904,56716,56766</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39368111$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Xiangjun</creatorcontrib><creatorcontrib>Shi, Xiaoyi</creatorcontrib><creatorcontrib>Liu, Xiao</creatorcontrib><creatorcontrib>Zhai, Xuanxiang</creatorcontrib><creatorcontrib>Li, Wenting</creatorcontrib><creatorcontrib>Hong, Wei</creatorcontrib><title>Eliminating Intracellular MRSA via Mannosylated Lipid-Coated Calcium Phosphate Nanoparticles</title><title>Molecular pharmaceutics</title><addtitle>Mol. Pharmaceutics</addtitle><description>Methicillin-resistant Staphylococcus aureus (MRSA) within cells proves exceptionally challenging to eradicate using conventional antimicrobials, resulting in recurring infections and heightened resistance. Herein, we reported an innovative mannosylated lipid-coated photodynamic/photothermal calcium phosphate nanoparticle (MAN-LCaP@ICG) for eradicating intracellular MRSA. The MAN-LCaP functioned as the vehicle for drug delivery, exhibiting preferential uptake by macrophages and facilitating the transport of ICG to intracellular pathogens. The MAN units integrated into MAN-LCaP@ICG could promote binding with MAN residuals on macrophage cells, as evidenced by cellular uptake assays using fluorescence microscopy and flow cytometry. Following its targeted accumulation, MAN-LCaP@ICG could enter into the cytoplasm and efficiently eradicate intracellular MRSA by a combination of the lysosome escape capability of CaP and the photodynamic and photothermal therapeutic effects of ICG. Furthermore, MAN-LCaP@ICG could kill MRSA more effectively than LCaP@ICG without MAN units or free ICG in a mouse peritoneal infection model. Therefore, MAN-LCaP@ICG provided a promising direction for human clinical application in combating intracellular infections.</description><subject>Animals</subject><subject>Anti-Bacterial Agents - administration & dosage</subject><subject>Anti-Bacterial Agents - chemistry</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Calcium Phosphates - chemistry</subject><subject>Female</subject><subject>Humans</subject><subject>Indocyanine Green - administration & dosage</subject><subject>Indocyanine Green - chemistry</subject><subject>Lipids - chemistry</subject><subject>Macrophages - drug effects</subject><subject>Mannose - chemistry</subject><subject>Methicillin-Resistant Staphylococcus aureus - drug effects</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Nanoparticles - chemistry</subject><subject>Photochemotherapy - methods</subject><subject>Photothermal Therapy - methods</subject><subject>RAW 264.7 Cells</subject><subject>Staphylococcal Infections - drug therapy</subject><issn>1543-8384</issn><issn>1543-8392</issn><issn>1543-8392</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkM1OwzAQhC0EoqXwCijcuKTYcRLbxyoqUKkFxM8NKdo6DnXlxMFOkPr2pLRU4sZpd6XZ2Z0PoSuCxwRH5AakH1fWNCtwFUjVteNYYsyYOEJDksQ05FREx4eexwN05v0a4yhOInqKBlTQlBNChuh9anSla2h1_RHM6tb1fsZ0BlyweH6ZBF8aggXUtfUbA60qgrludBFm9mfIwEjdVcHTyvr-m1YFD1DbBlyrpVH-HJ2UYLy62NcRerudvmb34fzxbpZN5iFElLUhjSSXTHHGueRQUBYlJUkpjiTjJStLzgmOE4EFsCJJKWFCsKVk8TKOsVDA6Qhd73wbZz875du80n6bA2plO59TQijlJOVpLxU7qXTWe6fKvHG6ArfJCc63cPMebv4Hbr6H2-9e7s90y0oVh81fmr0g2Qm2HmvbubpP_Q_jb9X2jeQ</recordid><startdate>20241104</startdate><enddate>20241104</enddate><creator>Chen, Xiangjun</creator><creator>Shi, Xiaoyi</creator><creator>Liu, Xiao</creator><creator>Zhai, Xuanxiang</creator><creator>Li, Wenting</creator><creator>Hong, Wei</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><orcidid>https://orcid.org/0000-0001-6926-8329</orcidid><orcidid>https://orcid.org/0000-0003-1986-3044</orcidid><orcidid>https://orcid.org/0000-0001-5591-8028</orcidid></search><sort><creationdate>20241104</creationdate><title>Eliminating Intracellular MRSA via Mannosylated Lipid-Coated Calcium Phosphate Nanoparticles</title><author>Chen, Xiangjun ; Shi, Xiaoyi ; Liu, Xiao ; Zhai, Xuanxiang ; Li, Wenting ; Hong, Wei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a237t-32c8c7e8788c8ad3725f16302c78f7ff881045909a7d56317997bc74b4409ea83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animals</topic><topic>Anti-Bacterial Agents - administration & dosage</topic><topic>Anti-Bacterial Agents - chemistry</topic><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Calcium Phosphates - chemistry</topic><topic>Female</topic><topic>Humans</topic><topic>Indocyanine Green - administration & dosage</topic><topic>Indocyanine Green - chemistry</topic><topic>Lipids - chemistry</topic><topic>Macrophages - drug effects</topic><topic>Mannose - chemistry</topic><topic>Methicillin-Resistant Staphylococcus aureus - drug effects</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Nanoparticles - chemistry</topic><topic>Photochemotherapy - methods</topic><topic>Photothermal Therapy - methods</topic><topic>RAW 264.7 Cells</topic><topic>Staphylococcal Infections - drug therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Xiangjun</creatorcontrib><creatorcontrib>Shi, Xiaoyi</creatorcontrib><creatorcontrib>Liu, Xiao</creatorcontrib><creatorcontrib>Zhai, Xuanxiang</creatorcontrib><creatorcontrib>Li, Wenting</creatorcontrib><creatorcontrib>Hong, Wei</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><jtitle>Molecular pharmaceutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Xiangjun</au><au>Shi, Xiaoyi</au><au>Liu, Xiao</au><au>Zhai, Xuanxiang</au><au>Li, Wenting</au><au>Hong, Wei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Eliminating Intracellular MRSA via Mannosylated Lipid-Coated Calcium Phosphate Nanoparticles</atitle><jtitle>Molecular pharmaceutics</jtitle><addtitle>Mol. Pharmaceutics</addtitle><date>2024-11-04</date><risdate>2024</risdate><volume>21</volume><issue>11</issue><spage>5772</spage><epage>5783</epage><pages>5772-5783</pages><issn>1543-8384</issn><issn>1543-8392</issn><eissn>1543-8392</eissn><abstract>Methicillin-resistant Staphylococcus aureus (MRSA) within cells proves exceptionally challenging to eradicate using conventional antimicrobials, resulting in recurring infections and heightened resistance. Herein, we reported an innovative mannosylated lipid-coated photodynamic/photothermal calcium phosphate nanoparticle (MAN-LCaP@ICG) for eradicating intracellular MRSA. The MAN-LCaP functioned as the vehicle for drug delivery, exhibiting preferential uptake by macrophages and facilitating the transport of ICG to intracellular pathogens. The MAN units integrated into MAN-LCaP@ICG could promote binding with MAN residuals on macrophage cells, as evidenced by cellular uptake assays using fluorescence microscopy and flow cytometry. Following its targeted accumulation, MAN-LCaP@ICG could enter into the cytoplasm and efficiently eradicate intracellular MRSA by a combination of the lysosome escape capability of CaP and the photodynamic and photothermal therapeutic effects of ICG. Furthermore, MAN-LCaP@ICG could kill MRSA more effectively than LCaP@ICG without MAN units or free ICG in a mouse peritoneal infection model. Therefore, MAN-LCaP@ICG provided a promising direction for human clinical application in combating intracellular infections.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>39368111</pmid><doi>10.1021/acs.molpharmaceut.4c00779</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0001-6926-8329</orcidid><orcidid>https://orcid.org/0000-0003-1986-3044</orcidid><orcidid>https://orcid.org/0000-0001-5591-8028</orcidid></addata></record> |
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| subjects | Animals Anti-Bacterial Agents - administration & dosage Anti-Bacterial Agents - chemistry Anti-Bacterial Agents - pharmacology Calcium Phosphates - chemistry Female Humans Indocyanine Green - administration & dosage Indocyanine Green - chemistry Lipids - chemistry Macrophages - drug effects Mannose - chemistry Methicillin-Resistant Staphylococcus aureus - drug effects Mice Mice, Inbred BALB C Nanoparticles - chemistry Photochemotherapy - methods Photothermal Therapy - methods RAW 264.7 Cells Staphylococcal Infections - drug therapy |
| title | Eliminating Intracellular MRSA via Mannosylated Lipid-Coated Calcium Phosphate Nanoparticles |
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