Modulation of immune responses by nanoparticles

NanomedicineVol. 16, No. 22 Journal WatchFree AccessModulation of immune responses by nanoparticlesChristina Janko, Ralf P Friedrich, Iwona Cicha, Harald Unterweger, Stefan Lyer & Christoph AlexiouChristina Janko https://orcid.org/0000-0001-5705-6329Department Otorhinolaryngology, Head Neck Surgery, Section Experimental Oncology Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-Professorship, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Glueckstr. 10a, 91054, GermanySearch for more papers this author, Friedrich https://orcid.org/0000-0001-6370-3545Department Cicha https://orcid.org/0000-0002-7399-5307Department Unterweger https://orcid.org/0000-0002-8335-0692Department https://orcid.org/0000-0003-2338-1136Department author Alexiou *Author correspondence: E-mail Address: [email protected]://orcid.org/0000-0003-2220-6790Department authorPublished Online:11 Aug 2021https://doi.org/10.2217/nnm-2021-0198AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInRedditEmail Keywords: autoimmune diseasesbone regenerationcancer immunotherapyhyperthermiaimmunomodulationMannose-derived carbon dots catch danger signals target them dendritic cellsEvaluation of: Zhou Q, Gong N, Zhang D, et al. Mannose-derived amplify microwave ablation-induced antitumor capturing and transferring ‘danger signals’ cells. ACS Nano 15(2), 2920–2932 (2021).Hepatocellular carcinoma is an increasing concern worldwide. In patients with contraindications surgical resection, ablation (MWA) represents a suitable locoregional, minimally invasive treatment technique [1]. However, the occurrence tumor recurrences metastases high. MWA lyses cells, leading release tumor-associated antigens, which could serve as in situ cancer vaccines. MWA-induced are often insufficient, due lack antigen uptake order improve MWA, synthesized derived from different sugars [2]. (Man-CD) were spherical hydrodynamic diameters 3 nm phosphate-buffered saline, or 7 serum. Upon cells various CDs preincubated lysates, only Man-CDs induced upregulation costimulatory markers CD80, CD86 CD40, well cytokines TNF-α, IL-6 IL-1β. other had no effect on indicating that efficiently caught tumor-derived components. Mass spectrometry revealed captured proteins known enhance [3], including damage-associated molecular patterns proinflammatory molecules such HSP 70 90, HMGB1, calreticulin histones. Next, vivo efficacy was investigated bilateral model mice. Tumors injection right flank (primary tumor), followed left 4 days later (distant tumor). When grown 10 × mm, primary tumors treated 0 3, intratumoral 100 μg at both time points. Control groups received therapy, alone only. After 14 days, smaller than untreated controls. distant tumors, there weak (Man-CDs) difference size. The combination Man-CD abolished growth prolonging survival. Flow cytometry increased numbers CD8+ T spleen, blood metastatic tissue. To mimic microenvironment clinical hepatocellular orthotopic constructed into tumor, matrigel livers tumors. model, inhibited their growth, but did not affect liver contrast, significantly confirming strong abscopal treatment. analyze memory, mice described subsequently rechallenged flank. Although delayed effective suppression extended survival, showing can induce long-term immunological memory protecting against tumors.– Written C JankoCell death immunomodulation via magnetic hyperthermia chitosan-coated Fe3O4Evaluation Chauhan A, Midha S, Kumar R Rapid inhibition regulated caspase time-dependent clearance iron oxide nanoparticles. Biomater. Sci. 9(8), 2972–2990 (2021).Temperature be important modulator adaptive immunity, influencing response infection, injury [4,5]. strongly modulates status through heat shock subsequent activation system [6]. developed Fe3O4 nanoparticles high heating efficiency evaluated after high-frequency (MHT) rat C6 glioblastoma [7].Magnetic (MNPs) prepared electrochemical method characterized x-ray powder diffraction, transmission electron microscopy, vibrating-sample magnetometry dynamic light scattering. nanoparticles, mostly morphology, crystalline structure diameter about 40 magnetization 71.5 emu/g. Normalization specific absorption rate measurements yielded values 9 nHm2/kg water culture medium, respectively, suggesting formation protein corona. Corona also indicated scattering measurements, showed narrow size distribution between 110 compared wider 40–320 media.To investigate efficiency, injected subcutaneously flanks rats. About later, animals 600–1000 (2 per mm3 volume) MHT temperature range 42–44°C. contrast control (alternating field MNP alone), where inhibitory progression detected, combined MNP/MHT resulted rapid 69.4% within 8 complete 32 recurrence recorded over 5 month follow-up.Furthermore, biological markers, glial (GFAP), cell proliferation (Ki67), angiogenesis (CD31) apoptosis (TUNEL cleaved caspase-3) assessed evaluate efficacy. controls, group ruptured vessels sections decrease GFAP Ki67 expression, density loss proliferative capacity. Increased expression TUNEL caspase-3 MNP/MHP group, minimal staining animals, enhanced apoptotic death.Compared pleiotropic cytokine upregulated triggering accelerated regression. Finally, biodistribution studies MNPs phagocytosis liver, negligible deposition organs heart, lung kidney.In summary, based apoptosis, reduced proliferation, disrupted vasculature stimulation system, authors demonstrated feasibility nanoparticles.– RP AlexiouAntigen-specific tolerance PEGylated nanoparticlesEvaluation Li PY, Bearoff F, Zhu PEGylation enables administered antigen-specific tolerance. J. Control. Release 331, 164–175 (2021).The self-tolerance resulting inflammatory autologous healthy tissues hallmark diseases. Currently, lifelong therapies available suffering diseases, Type I diabetes multiple sclerosis. These therapies, either alleviate symptoms globally suppress result adverse effects [8]. Using poly(lactic-co-glycolic acid) (PLGA-NPs) tolerogenic drugs has been proposed promising establish tolerance, most achieved treating disease before its onset [9,10]. This related fact PLGA-NPs themselves cause responses. recent study, hypothesized poly(ethylene glycol) (PEG) shell systemic [11].The PLGA–PEG-NPs encapsulated peptide MOG[35–55] relevant experimental encephalomyelitis (EAE), well-characterized mouse MOG–PLGA–PEG-NPs non-PEGylated counterparts similar (250–300 nm) peptide-loading MOG–PLGA–PEG-NPs, likely presence hydrophilic PEG domains trapped PLGA cores. Following extensive evaluation particle types vitro, tested EAE, Freund’s adjuvant, two injections pertussis toxin.Compared free MOG-PLGA-NPs, EAE underwent subcutaneous MOG-NPs severity manner. Subsequently, studied MOG–PLGA-NPs activation, complement vivo. observed locally site spleen. Further, trafficking lymph nodes spleen parallel IL-17 IL-22 splenocytes, lower MOG-specific number Tregs central nervous system. Collectively, migrate capable inducing response.The presented approach may thus constitute therapy train recognize ‘safe’, without attenuating protection pathogens.– CichaNanoparticle-based pH-responsive delivery activating drug resiquimodEvaluation Wagner J, Gößl Ustyanovska N Mesoporous silica carrier immune-activating resiquimod local 15, 4450–4466 (2021).Tumors have ability successfully evade host, limiting immunoactive [12]. One possibility circumvent problem boost maturation antigen-presenting Toll-like receptors [13].In work, path developing targeted multifunctional mesoporous (MSNs) anticancer immune-stimulant (R848) [14]. MSN cores modified phenyl accommodate hydrophobic R848 loading capacity 3.2 ± 0.5 ng/μg particles. A biotin–avidin complex bound acetal linker gatekeeper. Dynamic increase particles 146 280 binding complex. ζ potential isoelectric point shifted -50 mV pH 3.4 +20 9.07, because large N-termini avidin moiety. Successful functionalization confirmed Fourier transform infrared spectroscopy thermogravimetric capping pores proven nitrogen sorption measurements. shown remain particles’ least 60 h 37°C. lowering 5.5, corresponds lysosomes, sustained observed.Uptake these endolysosomes concentration-dependent manner using macrophage line, macrophages B Up concentration μg/ml, tolerated 24 incubation. Dendritic R848-loaded secretion amounts IL-12p40 CD80 MHC complex, R848.Subsequently, safety pharmacokinetics carriers C57BL/6 dose corresponding found main draining near site, manly migratory half-life particle-associated 18 117 min profile burst low steady release.Taken together, results provide proof-of-concept highlight authors’ MSN-based vehicle improved immunotherapy.– H UnterwegerSeeking inner balance bone regenerationEvaluation Zheng Z, Chen Y, Hong ‘Yin Yang’ immunomodulatory magnesium-enriched graphene nanoscrolls decorated biomimetic scaffolds promoting regeneration. Adv. Healthc. Mater. 10(2), 2000631 (2021).Autologous transplantation standard reconstruction major defects [15]. Because sources transplantable material scarce, new techniques like tissue engineering regeneration driven agents currently under investigation. commonly fail produce sufficient outcomes imbalance pro- anti-inflammatory triggers caused materials used. settings, play particularly role. As al., M1 phenotype activated Raw264.7 line (GO) (GNS) [16]. overcome limitation, magnesium immobilized wire-like GO constructs (MgNPs@GNS), producing Mg2+ ions. Interestingly, supplementing GNS ions led repolarization toward M2 induction healing processes. Furthermore, study TLR4-dependent internalization MgNPs@GNS accompanied GNS-induced reactive oxygen species levels downregulation NF-κB pathway. GO-stimulated initiated processes chemotactic attraction endothelial progenitor marrow stem Mg2+, migration further increased, additional enhancement pure demineralized matrix (DBM), DBM + cranial defect Micro-computed tomography slightly better outcome 6 12 weeks. biggest improvement, however, MgNPs@GNS, already weeks nearly degree seen At latter point, closed combination. angiography histomorphological examinations higher vascularization newly generated structures MgNPs@GNS. Taking addition MgNPs biocompatibility dramatically animal model. underscores importance balancing region disease/injury proves achieving goal choice components.– S LyerFinancial competing interests disclosureThe affiliations financial involvement any organization entity interest conflict subject matter discussed manuscript. includes employment, consultancies, honoraria, stock ownership options, expert testimony, grants patents pending, royalties.No writing assistance utilized production manuscript.References1. 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Casey LM, Pearson RM, Hughes KR Conjugation transforming factor beta antigen-loaded poly(lactide-co-glycolide) enhances Bioconjug. Chem. 29(3), 813–823 Scholar10. Northrup L, Griffin JD, Christopher MA Co-delivery autoantigen dexamethasone incomplete adjuvant ameliorates encephalomyelitis. 266, 156–165 (2017).Crossref, Scholar11. Scholar12. Whiteside TL. Immune cancer: therapeutic intervention. Semin. Biol. 16(1), 3–15 (2006).Crossref, Scholar13. Couzin-Frankel immunotherapy. Science 342(6165), 1432–1433 (2013).Crossref, Scholar14. Scholar15. Weigand Horch RE, Boos AM, Beier JP, Arkudas A. arteriovenous loop: axially vascularized Eur. 59(3–4), 286–299 Scholar16. Yang’of e2000631 ScholarFiguresReferencesRelatedDetails Vol. Follow us social media latest updates Metrics Downloaded 664 times History Received May 2021 Accepted 30 June Published online 11 August print September Information© Future Medicine LtdKeywordsautoimmune immunotherapyhyperthermiaimmunomodulationFinancial manuscript.PDF download