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Herein, an acidity\u2010responsive nanoreactor (Au@CaP\u2010Flu@HA) is fabricated for toxic acidosis and starvation synergistic therapy. In the nanoreactor, the fluvastatin (Flu) could reduce lactate efflux by inhibiting the lactate\u2010proton transporter (monocarboxylate transporters, MCT4), resulting in intracellular lactate accumulation. Meanwhile, the glucose oxidase\u2010mimic Au\u2010nanocomposite consumes glucose to induce cell starvation accompanied by gluconic acid production, coupling with lactate to exacerbate toxic acidosis. Also, the up\u2010regulated autophagic energy supply of tumor cells under energy deprivation and hypoxia aggravation is blocked by autophagy inhibitor CaP. Cellular dysfunction under pHi acidification and impaired Adenosine Triphosphate (ATP) synthesis under starvation synergistically promote tumor cell apoptosis. Both in vitro and in vivo studies demonstrate that this combinational approach of toxic\u2010acidosis\/starvation therapy could effectively destruct the \u201cWarburg Effect\u201d to inhibit tumor growth and anti\u2010metastatic effects.<\/jats:p>","DOI":"10.1002\/smll.202304058","type":"journal-article","created":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T05:51:40Z","timestamp":1689918700000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Acidity\u2010Responsive Nanoreactors Destructed \u201cWarburg Effect\u201d for Toxic\u2010Acidosis and Starvation Synergistic Therapy"],"prefix":"10.1002","volume":"19","author":[{"given":"Jiawei","family":"Zhu","sequence":"first","affiliation":[{"name":"Key Laboratory of Flexible Electronics (KLOFE) and Institute of Advanced Materials (IAM) School of Physical and Mathematical Sciences Nanjing Tech University (NanjingTech)  Nanjing 211816 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