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However, the mononuclear phagocyte system (MPS) and the drug protonation after nanoparticles (NPs) burst release still limit the drug delivery efficiency. In this work, a self\u2010disguised Nanospy is designed to overcome this problem. The Nanospy is composed of: i) poly (lactic\u2010co\u2010glycolic acid)\u2010polyethylene glycol (PLGA\u2010PEG) loading doxorubicin is the core structure of the Nanospy. ii) CD47 mimic peptides (CD47p) is linked to NPs which conveyed the \u201cdon't eat me\u201d signal. iii) 4\u2010(2\u2010aminoethyl) benzenesulfonamide (AEBS) as the inhibitor of Carbonic anhydrase IX (CAIX) linked to NPs. Briefly, when the Nanospy circulates in the bloodstream, CD47p binds to the regulatory protein \u03b1 (SIRP\u03b1) on the surface of macrophages, which causes the Nanospy escapes from phagocytosis. Subsequently, the Nanospy enriches in tumor and the AEBS reverses the acidic microenvironment of tumor. Due to above characteristics, the Nanospy reduces liver macrophage phagocytosis by 25% and increases tumor in situ DOX concentration by 56% compared to PLGA@DOX treatment. In addition, the Nanospy effectively inhibits tumor growth with a 63% volume reduction. This work presents a unique design to evade the capture of MPS and overcomes the influence of acidic tumor microenvironment (TME) on weakly alkaline drugs.<\/jats:p>","DOI":"10.1002\/smll.202300060","type":"journal-article","created":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T11:02:26Z","timestamp":1679050946000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A Self\u2010Disguised Nanospy for Improving Drug Delivery Efficiency via Decreasing Drug Protonation"],"prefix":"10.1002","volume":"19","author":[{"given":"Kuo","family":"Zhang","sequence":"first","affiliation":[{"name":"NHC and CAMS Key Laboratory of Molecular Probe and Targeted Theranostics Harbin Medical University  Harbin 150001 P. R. China"},{"name":"Heilongjiang Key Laboratory of Scientific Research in Urology Harbin Medical University  Harbin 150001 P. R. 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