{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:32:49Z","timestamp":1785407569976,"version":"3.56.0"},"reference-count":60,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,11,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Cryptococcus neoformans<\/jats:italic>\n                      is a significant and pathogenic\n                        encapsulated basidiomycete fungus responsible for cryptococcosis,\n                        particularly in immunocompromised individuals. With increasing incidence\n                        rates globally, there is an urgent need for improved therapeutic strategies.\n                        This study presents the development of a fungal-targeted nanodrug delivery\n                        system utilizing a calcofluor white-phosphatidylethanolamine conjugate\n                        (CFW-PEc) to enhance the delivery and efficacy of amphotericin B against\n                      <jats:italic toggle=\"yes\">C. neoformans<\/jats:italic>\n                      . We successfully formulated AmB-loaded\n                        CFW-PEc-ethosomes, which demonstrated favorable physicochemical properties,\n                        including suitable particle size, zeta potential, and high drug entrapment\n                        efficiency.\n                      <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                      antifungal assessments revealed that\n                        CFW-PEc-AmB-ethosomes exhibited superior antifungal activity compared to\n                        conventional AmB formulations, maintaining high inhibition rates at lower\n                        concentrations, while also demonstrating a favorable safety profile with\n                        reduced cytotoxicity. Additionally,\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      studies in a\n                        mouse model of cryptococcal pneumonia illustrated remarkable reductions in\n                        fungal burdens and improved histopathological outcomes, attributing these\n                        effects to effective targeting of\n                      <jats:italic toggle=\"yes\">C. neoformans<\/jats:italic>\n                      via\n                        CFW-PEc. Our findings underscore the potential of CFW-PEc in enhancing the\n                        therapeutic efficacy and safety profile of antifungal treatments, paving the\n                        way for advanced treatment strategies against cryptococcal pneumonia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Cryptococcal pneumonia presents a significant global health burden with\n                        limited therapeutic options due to inherent toxicity and suboptimal\n                        bioavailability of conventional antifungal agents. This investigation\n                        demonstrates the innovative application of calcofluor\n                        white-phosphatidylethanolamine conjugate (CFW-PEc) to enhance amphotericin B\n                        (AmB) delivery via ethosomes for cryptococcal infection treatment. Our\n                        findings elucidate that CFW-PEc significantly potentiates the antifungal\n                        efficacy of AmB-loaded ethosomes against\n                      <jats:italic toggle=\"yes\">Cryptococcus\n                            neoformans<\/jats:italic>\n                      while concomitantly mitigating associated\n                        cytotoxicity at optimal concentrations. In murine models of pulmonary\n                        cryptococcosis, this novel formulation achieved a remarkable 10-fold\n                        reduction in fungal burden compared to controls, while preserving pulmonary\n                        histoarchitecture and attenuating inflammatory responses. This delivery\n                        system\u2019s integrated strategy of increasing antifungal effectiveness\n                        while reducing adverse effects marks a significant leap forward in\n                        developing safer and more targeted nanomaterial-mediated antifungal\n                        treatments. These results have profound implications for developing more\n                        efficacious and less toxic treatment modalities for cryptococcal pneumonia\n                        and potentially other invasive fungal infections.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.01729-25","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T13:34:57Z","timestamp":1758807297000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Advancing antifungal therapy: exploring targeted CFW-PEc-enhanced                    ethosomal formulations of amphotericin B against cryptococcal                    pneumonia"],"prefix":"10.1128","volume":"13","author":[{"given":"Guoting","family":"Shi","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/008w1vb37","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Pharmacy, Binzhou Medical University","place":["Yantai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengshun","family":"Li","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/008w1vb37","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Pharmacy, Binzhou Medical University","place":["Yantai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Chu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/008w1vb37","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Pharmacy, Binzhou Medical University","place":["Yantai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baocheng","family":"Tian","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/008w1vb37","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Pharmacy, Binzhou Medical University","place":["Yantai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengxin","family":"Li","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/008w1vb37","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Pharmacy, Binzhou Medical University","place":["Yantai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/008w1vb37","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Pharmacy, Binzhou Medical University","place":["Yantai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huihui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of pathology, Affiliated Yuhuangding Hospital of Qingdao University","place":["Yantai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanchun","family":"Han","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/008w1vb37","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Pharmacy, Binzhou Medical University","place":["Yantai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8347-7917","authenticated-orcid":false,"given":"Chunxiao","family":"Meng","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/008w1vb37","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Pharmacy, Binzhou Medical University","place":["Yantai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9195-2255","authenticated-orcid":false,"given":"Chen","family":"Ding","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02ahky613","id-type":"ROR","asserted-by":"publisher"}],"name":"College of Life and Health Science, Northeastern University","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7665-0128","authenticated-orcid":true,"given":"Sixiang","family":"Sai","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/008w1vb37","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Pharmacy, Binzhou Medical University","place":["Yantai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.05273-11"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2015.6"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40249-023-01073-4"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(17)30303-1"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(17)30243-8"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1086\/649858"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.7.4225-4237.2000"},{"key":"e_1_3_4_9_2","first-page":"871","article-title":"Cryptococcus neoformans survive and\n                        replicate in human microglia","volume":"73","author":"Lee SC","year":"1995","unstructured":"Lee SC, Kress Y, Zhao ML, Dickson DW, Casadevall A. 1995. Cryptococcus neoformans survive and replicate in human microglia. Lab Invest 73:871\u2013879.","journal-title":"Lab Invest"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2024.07.002"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1080\/1061186X.2017.1331352"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1139\/cjm-2017-0749"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S93105"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-013-0069-4"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2007.05872.x"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000227"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0609848104"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2006.05551.x"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.4.11.1902-1912.2005"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1567-1364.2005.00017.x"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2007.05695.x"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M708927200"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwy030"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02821413"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0507.1993.tb00757.x"},{"key":"e_1_3_4_26_2","first-page":"616","article-title":"Rapid detection of fungi in tissues using\n                        calcofluor white and fluorescence microscopy","volume":"108","author":"Monheit JE","year":"1984","unstructured":"Monheit JE, Cowan DF, Moore DG. 1984. Rapid detection of fungi in tissues using calcofluor white and fluorescence microscopy. Arch Pathol Lab Med 108:616\u2013618.","journal-title":"Arch Pathol Lab Med"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.170.4.1945-1949.1988"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1439-0507.2003.00857.x"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1080\/09546630802449070"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S488456"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00025-19"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00715-19"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40694-021-00126-3"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.2c00388"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2015.02.043"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules30142892"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10856-025-06914-2"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2006.03.006"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2017.09.028"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40259-018-0290-5"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dks379"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2022.114614"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2017.03.019"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2017.11.031"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2004.07.050"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemosphere.2023.140147"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1399937"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2025.114681"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2024.113918"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02264-19"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2013.05.006"},{"key":"e_1_3_4_52_2","first-page":"45","article-title":"Cellular uptake of coumarin-6 as a model\n                        drug loaded in solid lipid nanoparticles","volume":"62","author":"Rivolta I","year":"2011","unstructured":"Rivolta I, Panariti A, Lettiero B, Sesana S, Gasco P, Gasco MR, Masserini M, Miserocchi G. 2011. Cellular uptake of coumarin-6 as a model drug loaded in solid lipid nanoparticles. J Physiol Pharmacol 62:45\u201353.","journal-title":"J Physiol Pharmacol"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2015.01.022"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.3389\/ffunb.2023.1183291"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-3722-7_21"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1007295107"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-06948-0"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2025.107216"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-023-01800-x"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1007\/s42770-020-00248-7"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkac351"}],"container-title":["Microbiology Spectrum"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.01729-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.01729-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T14:09:43Z","timestamp":1762265383000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/spectrum.01729-25"}},"subtitle":[],"editor":[{"given":"Renato","family":"Kovacs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,11,4]]},"references-count":60,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11,4]]}},"alternative-id":["10.1128\/spectrum.01729-25"],"URL":"https:\/\/doi.org\/10.1128\/spectrum.01729-25","relation":{},"ISSN":["2165-0497"],"issn-type":[{"value":"2165-0497","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,4]]},"assertion":[{"value":"2025-06-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01729-25"}}