Artificial “Nano-Targeted Cells” for Bimodal Imaging-Guided Tumor Cocktail Therapy

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Abstract

Abstract Background: Single therapeutic modality always has its limitations in combating metastatic lesions with complicacy. Although the emerging immunotherapy exhibits preliminary success, solid tumors are usually immunosuppressive, leading to ineffective antitumor immune responses and immunotherapeutic resistance. Rational combination of several therapeutic modalities may potentially become a new therapeutic strategy to effectively combat cancer.Results: Poly lactic-co-glycolic acid (PLGA) nanospheres were constructed with photothermal transduction agents (PTAs)- Prussian blue (PB) encapsulated in the core and chemotherapeutic docetaxel (DTX)/ immune adjuvant- imiquimod (R837) loaded in the shell. Tumor cell membranes were further coated outside PLGA nanospheres (designated as “M@P-PDR”), which acted as “Nano-targeted cells” to actively accumulate in tumor sites, which was guided/monitored by photoacoustic (PA)/ magnetic resonance (MR) imaging. Upon laser irradiation, photothermal effects were triggered. Combined with DTX, PTT induced in situ tumor eradication. Assisted by immune adjuvant R837, the maturation of DCs were promoted. Besides, DTX polarized M2-phenotype tumor-associated macrophages (TAMs) to M1-phenotype, relieving immunosuppressive TME. Integrating the above processes, the infiltration of cytotoxic T lymphocytes (CTLs) increased. The primary tumors and metastasis were significantly inhibited when treated with “Nano-targeted cells” based cocktail therapy.Conclusion: “Nano-targeted cells” based therapeutic cocktail therapy is a promising approach to promote tumor regression and counter metastasis/ recurrence.
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Artificial “Nano-Targeted Cells” for Bimodal Imaging-Guided Tumor Cocktail Therapy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Artificial “Nano-Targeted Cells” for Bimodal Imaging-Guided Tumor Cocktail Therapy Qiaoqi Chen, Liang Zhang, Lin Li, Mixiao Tan, Weiwei Liu, Shuling Liu, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-934186/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 18 You are reading this latest preprint version Abstract Background : Single therapeutic modality always has its limitations in combating metastatic lesions with complicacy. Although the emerging immunotherapy exhibits preliminary success, solid tumors are usually immunosuppressive, leading to ineffective antitumor immune responses and immunotherapeutic resistance. Rational combination of several therapeutic modalities may potentially become a new therapeutic strategy to effectively combat cancer. Results : Poly lactic-co-glycolic acid (PLGA) nanospheres were constructed with photothermal transduction agents (PTAs)- Prussian blue (PB) encapsulated in the core and chemotherapeutic docetaxel (DTX)/ immune adjuvant- imiquimod (R837) loaded in the shell. Tumor cell membranes were further coated outside PLGA nanospheres (designated as “M@P-PDR”), which acted as “Nano-targeted cells” to actively accumulate in tumor sites, which was guided/monitored by photoacoustic (PA)/ magnetic resonance (MR) imaging. Upon laser irradiation, photothermal effects were triggered. Combined with DTX, PTT induced in situ tumor eradication. Assisted by immune adjuvant R837, the maturation of DCs were promoted. Besides, DTX polarized M2-phenotype tumor-associated macrophages (TAMs) to M1-phenotype, relieving immunosuppressive TME. Integrating the above processes, the infiltration of cytotoxic T lymphocytes (CTLs) increased. The primary tumors and metastasis were significantly inhibited when treated with “Nano-targeted cells” based cocktail therapy. Conclusion : “Nano-targeted cells” based therapeutic cocktail therapy is a promising approach to promote tumor regression and counter metastasis/ recurrence. Nanoscience Biotechnology and Bioengineering Cocktail therapy Photothermal therapy Immunosuppressive tumor microenvironment Homologous targeting Nanomedicine Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Full Text Supplementary Files GraphicAbstract.pdf SupplementaryMaterial.pdf schema1.png Scheme 1. Schematic diagram of the homologous targeted tumor cocktail therapy based on M@P-PDR “Nano-targeted cells”. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revision 31 Oct, 2021 Review # 1 received at journal 09 Oct, 2021 Reviewer # 6 agreed at journal 30 Sep, 2021 Review # 5 received at journal 28 Sep, 2021 Reviews received at journal 27 Sep, 2021 Reviewer # 4 agreed at journal 27 Sep, 2021 Reviewer # 5 agreed at journal 27 Sep, 2021 Reviewers invited by journal 27 Sep, 2021 Reviewer # 3 agreed at journal 27 Sep, 2021 Review # 4 received at journal 27 Sep, 2021 Review # 3 received at journal 27 Sep, 2021 Review # 2 received at journal 27 Sep, 2021 Editor assigned by journal 27 Sep, 2021 Reviewer # 2 agreed at journal 26 Sep, 2021 Reviewer # 1 agreed at journal 26 Sep, 2021 Editor invited by journal 26 Sep, 2021 Submission checks completed at journal 26 Sep, 2021 First submitted to journal 23 Sep, 2021 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-934186","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research","associatedPublications":[],"authors":[{"id":54315846,"identity":"6f922d16-a438-4626-b4db-aedeb31a5028","order_by":0,"name":"Qiaoqi Chen","email":"","orcid":"","institution":"Chongqing Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Qiaoqi","middleName":"","lastName":"Chen","suffix":""},{"id":54315847,"identity":"67b84c13-253c-4328-bbd9-174d1d04a34f","order_by":1,"name":"Liang Zhang","email":"","orcid":"","institution":"Chongqing Medical 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(A) Schematic illustration of the synthetic process for M@P-PDR nanospheres. (B) SEM image of M@P-PDR. (C1) TEM image of P-PDR; (C2) TEM image of M@P-PDR. (D) SDS-PAGE protein analysis results of cancer cell membrane vesicles, M@P-PDR and P-PDR. (E) DLS results of P-PDR and M@P-PDR nanospheres. (F) Zeta-potential of P-PDR and M@P-PDR nanospheres. (G) UV-Vis-NIR spectra of PB NPs, M@P-DR and M@P-PDR suspensions.","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-934186/v1/f0a09b95fcd2c6dd02e3267f.png"},{"id":14083032,"identity":"ae80cd7e-ba32-42db-b9a4-99cfa8972829","added_by":"auto","created_at":"2021-09-28 19:20:44","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1525309,"visible":true,"origin":"","legend":"(A) Infrared thermal images of M@P-PDR at a concentration of 5 mg mL-1 under 808 nm laser irradiation at different power densities (0.75, 1.00, 1.25 and 1.50 W cm-2), and (B) the corresponding temperature-time curves of M@P-PDR at different power densities. (C) Infrared thermal images of M@P-PDR at different concentrations (0, 1, 2, 3, 4 and 5 mg mL-1) under 808 nm laser (1.5 W cm˗2, 5 min) irradiation, and (D) the corresponding photothermal temperature-time curves of M@P-PDRs at different concentrations. (E) Temperature change curves of M@P-PDR over five laser irradiation on/off cycles. (F) Linear relationship between PA intensities and M@P-PDR concentrations, and the corresponding in vitro PA images (inset). (G) T1 relaxation rate of M@P-PDR and the corresponding in vitro MR images (inset).","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-934186/v1/10547fbcb48df10dbaa30545.png"},{"id":14083223,"identity":"1d704645-5ad4-413f-89c2-cbbbd2d69156","added_by":"auto","created_at":"2021-09-28 19:23:45","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1204388,"visible":true,"origin":"","legend":"(A) CLSM images of 4T1 cells treated with M@P-PDR and P-PDR nanospheres for different times (0.5, 1, 2, 3 and 4 h), respectively (the blue indicates nucleus stained with DAPI, the red indicates M@P-PDR or P-PDR nanospheres stained with DiI), and (B) the corresponding flow cytometry quantitative analyses.","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-934186/v1/b73e098c0c524b330d52872d.png"},{"id":14083031,"identity":"fdaceaa9-3e0c-4ea4-b828-b591c26831bb","added_by":"auto","created_at":"2021-09-28 19:20:44","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":2466691,"visible":true,"origin":"","legend":"In vitro therapeutic effects of M@P-PDR. (A) CCK8 results after various treatments. (B) CLSM images of 4T1 cells co-stained with CAM and PI after various treatments to distinguish the live (green fluorescence) and dead (red fluorescence) cells. (C) Flow cytometry results after various treatments.","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-934186/v1/330fef3756b691cce71d6a93.png"},{"id":14083035,"identity":"95ab370f-26d6-420a-926f-dc7b80d6b574","added_by":"auto","created_at":"2021-09-28 19:20:45","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":1316030,"visible":true,"origin":"","legend":"(A) The design scheme of the transwell system experiment. (B–C) The expression levels of CD11c+, CD86+and CD80+on the surface of DCs analyzed by flow cytometry after different treatments. (D–F) The secretion of IL-6, IL-12 and TNF-α in DC suspensions after different treatments.","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-934186/v1/1032685e69127212d5a3104a.png"},{"id":14083037,"identity":"8dbb5f44-c19e-4227-9ade-d33e7caecb5c","added_by":"auto","created_at":"2021-09-28 19:20:45","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":1763949,"visible":true,"origin":"","legend":"Biodistribution and in vivo MR/PA bimodal imaging of M@P-PDR. (A) Fluorescence images of 4T1 tumor-bearing mice at different time points (pre-injection, 1, 2, 4, 6, 8 and 24 h), and (B) the corresponding fluorescence intensities of tumors. (C) In vivo PA images of tumors and (E) the corresponding signal intensities (D) T1-weighted MR images and (F) the corresponding PSIE of tumors.","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-934186/v1/93ef33e629aebe649eadb6f7.png"},{"id":14083040,"identity":"5b0c6908-017e-4f3e-a7c1-2c5ec351b82a","added_by":"auto","created_at":"2021-09-28 19:20:45","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":1661137,"visible":true,"origin":"","legend":"In vivo photothermal performance of the M@P-PDR “Nano-targeted cells”. (A) Schematic illustration of the in vivo experimental design. (B) Infrared thermal images of 4T1 tumor-bearing Balb/c mice under different treatment groups. (C) Photothermal temperature-time curves of the eight groups under laser irradiation. and (D) of the corresponding temperature changes at tumor sites during irradiation.","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-934186/v1/5c5ed7a15e92fea00b7c3d9a.png"},{"id":14083224,"identity":"7f9c33cd-2b16-4822-9bbc-c30f27ed50ea","added_by":"auto","created_at":"2021-09-28 19:23:45","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":796991,"visible":true,"origin":"","legend":"Degree of in vivo DCs maturation and polarization of TAMs based on M@P-PDR “Nano-targeted cells”. (A) Flow cytometric analysis of DCs maturation in primary tumors (1st) of mice in different treatment groups. and (B) the corresponding quantification of DCs maturation. (C) Flow cytometric analysis of M2-TAMs (CD206+ F4/80+ CD11b+) in primary tumors (1st) and (D) the corresponding quantification of M2-TAMs. (E) Flow cytometric analysis of M1-TAMs (CD80+ F4/80+ CD11b+) in primary tumors (1st) and (F) the corresponding quantification of M1-TAMs.","description":"","filename":"8.png","url":"https://assets-eu.researchsquare.com/files/rs-934186/v1/0617805289e9bf7c5af4c39d.png"},{"id":14083039,"identity":"0d0f634e-60d2-4e68-bf27-7b3d6eb4c5a7","added_by":"auto","created_at":"2021-09-28 19:20:45","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":960875,"visible":true,"origin":"","legend":"In vivo immunostimulatory effects based on M@P-PDR “Nano-targeted cells”. (A-D) The secretion levels of IL-6, IL-12, TNF-α and IL-10 measured by ELISA assay. (E) Flow cytometric analysis of CD8+ T cell in the spleens of mice in different groups. (F) Quantification of CD8+ T cells.","description":"","filename":"9.png","url":"https://assets-eu.researchsquare.com/files/rs-934186/v1/a19372e7ce2bcc23fcffb4c2.png"},{"id":14083041,"identity":"f64b1381-cf43-42d4-8a84-128053ba0c94","added_by":"auto","created_at":"2021-09-28 19:20:45","extension":"png","order_by":10,"title":"Figure 10","display":"","copyAsset":false,"role":"figure","size":3782524,"visible":true,"origin":"","legend":"Anti-tumor effects of cocktail therapy based on M@P-PDR “Nano-targeted cells”. (A) Digital photos of 4T1 tumors on both sides in vivo and ex vivo on day 27 after different treatments. (B) Growth curves of the primary tumors (1st) and (C) the distant tumors (2nd) in different groups. (D) H\u0026E staining, TUNEL staining and HSP70 staining images of the primary tumor (1st) excised at day 3 after different treatments, and PCNA staining images of the distant tumor (2nd) excised at day 9 after different treatments.","description":"","filename":"10.png","url":"https://assets-eu.researchsquare.com/files/rs-934186/v1/8cd76413911d2c744c5ea433.png"},{"id":14083226,"identity":"25d650fa-3842-42a0-8353-762bd924c1dd","added_by":"auto","created_at":"2021-09-28 19:23:59","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1176827,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript20210923.pdf","url":"https://assets-eu.researchsquare.com/files/rs-934186/v1_covered.pdf"},{"id":14083221,"identity":"52e893c5-810b-4fee-8173-7b9d05a82085","added_by":"auto","created_at":"2021-09-28 19:23:44","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":115412,"visible":true,"origin":"","legend":"","description":"","filename":"GraphicAbstract.pdf","url":"https://assets-eu.researchsquare.com/files/rs-934186/v1/ce58ef75de6576366f2ffb31.pdf"},{"id":14083042,"identity":"d5e53f8d-5b7e-4ac8-84d5-0c868b19bc3c","added_by":"auto","created_at":"2021-09-28 19:20:45","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":2229641,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterial.pdf","url":"https://assets-eu.researchsquare.com/files/rs-934186/v1/8fe76064c0a610d06845e29d.pdf"},{"id":14083043,"identity":"435acc53-c567-4059-baa1-900ad32579e0","added_by":"auto","created_at":"2021-09-28 19:20:45","extension":"png","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":1658963,"visible":true,"origin":"","legend":"Scheme 1. Schematic diagram of the homologous targeted tumor cocktail therapy based on M@P-PDR “Nano-targeted cells”.","description":"","filename":"schema1.png","url":"https://assets-eu.researchsquare.com/files/rs-934186/v1/df9fb26b33052fafb40463f5.png"}],"financialInterests":"","formattedTitle":"\u003cp\u003eArtificial “Nano-Targeted Cells” for Bimodal Imaging-Guided Tumor Cocktail Therapy\u003c/p\u003e","fulltext":[{"header":"Full Text","content":"This preprint is available for \u003ca href='/article/rs-934186/latest.pdf' target='_blank'\u003edownload as a PDF\u003c/a\u003e."}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-nanobiotechnology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jnan","sideBox":"Learn more about [Journal of Nanobiotechnology](http://jnanobiotechnology.biomedcentral.com)","snPcode":"12951","submissionUrl":"https://submission.nature.com/new-submission/12951/3","title":"Journal of Nanobiotechnology","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Cocktail therapy, Photothermal therapy, Immunosuppressive tumor microenvironment, Homologous targeting, Nanomedicine","lastPublishedDoi":"10.21203/rs.3.rs-934186/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-934186/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Single therapeutic modality always has its limitations in combating metastatic lesions with complicacy. Although the emerging immunotherapy exhibits preliminary success, solid tumors are usually immunosuppressive, leading to ineffective antitumor immune responses and immunotherapeutic resistance. Rational combination of several therapeutic modalities may potentially become a new therapeutic strategy to effectively combat cancer.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Poly lactic-co-glycolic acid (PLGA) nanospheres were constructed with photothermal transduction agents (PTAs)- Prussian blue (PB) encapsulated in the core and chemotherapeutic docetaxel (DTX)/ immune adjuvant- imiquimod (R837) loaded in the shell. Tumor cell membranes were further coated outside PLGA nanospheres (designated as “M@P-PDR”), which acted as “Nano-targeted cells” to actively accumulate in tumor sites, which was guided/monitored by photoacoustic (PA)/ magnetic resonance (MR) imaging. Upon laser irradiation, photothermal effects were triggered. Combined with DTX, PTT induced \u003cem\u003ein situ\u003c/em\u003e tumor eradication. Assisted by immune adjuvant R837, the maturation of DCs were promoted. Besides, DTX polarized M2-phenotype tumor-associated macrophages (TAMs) to M1-phenotype, relieving immunosuppressive TME. Integrating the above processes, the infiltration of cytotoxic T lymphocytes (CTLs) increased. The primary tumors and metastasis were significantly inhibited when treated with “Nano-targeted cells” based cocktail therapy.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: “Nano-targeted cells” based therapeutic cocktail therapy is a promising approach to promote tumor regression and counter metastasis/ recurrence.\u003c/p\u003e","manuscriptTitle":"Artificial “Nano-Targeted Cells” for Bimodal Imaging-Guided Tumor Cocktail Therapy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-09-28 19:20:43","doi":"10.21203/rs.3.rs-934186/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2021-11-01T00:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2021-10-10T00:00:00+00:00","index":1,"fulltext":"Recommendation: Reviewer's comments unavailable due to the journal's policy.\n"},{"type":"reviewerAgreed","content":"","date":"2021-10-01T00:00:00+00:00","index":6,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2021-09-29T00:00:00+00:00","index":5,"fulltext":"Recommendation: Reviewer's comments unavailable due to the journal's policy.\n"},{"type":"editorInvitedReview","content":"","date":"2021-09-28T01:09:19+00:00","index":0,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2021-09-28T01:00:00+00:00","index":4,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2021-09-28T01:00:00+00:00","index":5,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2021-09-28T00:29:08+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2021-09-28T00:00:00+00:00","index":3,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2021-09-28T00:00:00+00:00","index":4,"fulltext":"Recommendation: Reviewer's comments unavailable due to the journal's policy.\n"},{"type":"editorInvitedReview","content":"","date":"2021-09-28T00:00:00+00:00","index":3,"fulltext":"Recommendation: Reviewer's comments unavailable due to the journal's policy.\n"},{"type":"editorInvitedReview","content":"","date":"2021-09-28T00:00:00+00:00","index":2,"fulltext":"Recommendation: Reviewer's comments unavailable due to the journal's policy.\n"},{"type":"editorAssigned","content":"","date":"2021-09-27T11:01:25+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2021-09-27T01:00:00+00:00","index":2,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2021-09-27T00:00:00+00:00","index":1,"fulltext":""},{"type":"editorInvited","content":"","date":"2021-09-26T23:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2021-09-26T11:35:33+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Nanobiotechnology","date":"2021-09-23T12:36:39+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-nanobiotechnology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jnan","sideBox":"Learn more about [Journal of Nanobiotechnology](http://jnanobiotechnology.biomedcentral.com)","snPcode":"12951","submissionUrl":"https://submission.nature.com/new-submission/12951/3","title":"Journal of Nanobiotechnology","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5ab09fc3-a4ba-47eb-9b17-2af6eabdab77","owner":[],"postedDate":"September 28th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":7503661,"name":"Nanoscience"},{"id":7503662,"name":"Biotechnology and Bioengineering"}],"tags":[],"updatedAt":"2021-12-10T14:58:45+00:00","versionOfRecord":[],"versionCreatedAt":"2021-09-28 19:20:43","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-934186","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-934186","identity":"rs-934186","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

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