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Localized target delivery of nanomedicine provides a promising solution for superior antitumor effect in superficial tumors, but its delivery efficiency can be greatly hampered by the dense tumor stroma. Compared with external modulation against the tumor extracellular matrix by physical methods, internal regulation of the tumor microenvironment via enzyme enables more direct degradation of the tumor extracellular matrix and robust antitumor efficacy. Herein, we report a dual\u2010enzyme delivery nanoplatform to impart a cascade catalytic reaction for potent chemodynamic therapy with enhanced penetration depth in the superficial tumor. In response to the tumor microenvironment, the glucose oxidase\/papain complex loaded in MnO\n                    <jats:sub>2<\/jats:sub>\n                    nanoparticles could be rapidly released to trigger cascade chemodynamic therapy and grant deeper penetration of therapeutic effect in the superficial tumor. The collective actions of papain's protease and peroxidase\u2010like activity allowed significant tumor penetration and reactive oxygen species production cascaded with glucose oxidase, holding great promise as a potential strategy to improve the efficacy of superficial tumor treatment.\n                  <\/jats:p>","DOI":"10.1002\/jbm.a.70149","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T10:50:16Z","timestamp":1788519016000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual Enzyme\u2010Loading\n                    <scp>\n                      MnO\n                      <sub>2<\/sub>\n                    <\/scp>\n                    Nanosystem for Cascade Chemodynamic Therapy With Enhanced Penetration in Superficial Tumors"],"prefix":"10.1002","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5697-8100","authenticated-orcid":false,"given":"Yingwei","family":"Tang","sequence":"first","affiliation":[{"name":"School of Chemistry, Chemical Engineering and Biotechnology Nanyang Technological University  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Li","sequence":"additional","affiliation":[{"name":"School of Chemistry, Chemical Engineering and Biotechnology Nanyang Technological University  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8453-2527","authenticated-orcid":false,"given":"Bo","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Chemistry, Chemical Engineering and Biotechnology Nanyang Technological University  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2841-3344","authenticated-orcid":false,"given":"Hongwei","family":"Duan","sequence":"additional","affiliation":[{"name":"School of Chemistry, Chemical Engineering and Biotechnology Nanyang Technological University  Singapore Singapore"},{"name":"Lee Kong Chian School of Medicine Nanyang Technological University  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222111694"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/20503121211034366"},{"key":"e_1_2_9_4_1","first-page":"32","article-title":"Biological Therapy: A New Age of Cancer Treatment","volume":"1","author":"Phan N. 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