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However, conventional inorganic adjuvants like Alum generally elicit Th2\u2010biased immune response. Despite recent efforts in developing organic adjuvants to mimic bacterial or viral infections for generating Th1 immunity, excessive inflammation remains a major concern. Herein, a new class of Th1\u2010biased adjuvant is reported via passivation engineering of zinc peroxide nanoparticles (p\u2010ZPNs) for potentiating the immunogenicity of cancer vaccines. p\u2010ZPNs show improved biocompatibility compared to unpassivated ZPNs due to retarded zinc ion release and hydrogen peroxide production, as well as efficient cellular uptake, endosome escape, dendritic cell maturation and antigen cross presentation. Mechanistic study indicates the intrinsic activity of p\u2010ZPNs to activate toll\u2010like receptors (TLR)\u20102, 4, and 6, triggering the TLR\/Myeloid differentiation primary response 88 (MyD88)\/Nuclear factor kappa\u2010light\u2010chain\u2010enhancer of activated B cells (NF\u2010\u03baB) axis for producing proinflammatory cytokines and therefore a robust Th1 immunity. Biosafety evaluation has shown the importance of the passivation engineering of ZPNs in reducing safety risks. Furthermore, in a p\u2010ZPNs\u2010based autologous cancer vaccine model, potent immune response is demonstrated in the inhibition of B16F10 tumors in both prophylactic and therapeutic vaccination settings. These findings suggest the great potential of p\u2010ZPN adjuvants for future Th1\u2010biased vaccine development.<\/jats:p>","DOI":"10.1002\/smll.202505250","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T11:02:23Z","timestamp":1756206143000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Passivation\u2010Engineered Zinc Peroxide Nanoparticles as Th1\u2010Biased Adjuvant for Antitumor Immunity"],"prefix":"10.1002","volume":"21","author":[{"given":"Jiangqi","family":"Luo","sequence":"first","affiliation":[{"name":"South Australian immunoGENomics Cancer Institute The University of Adelaide  Adelaide South Australia 5000 Australia"},{"name":"Australian Institute for Bioengineering and Nanotechnology The University of Queensland  Brisbane Queensland 4072 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