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Antibody\u2010based strategies utilizing TRIM21\u2010mediated targeted protein degradation (TPD), such as TRIM\u2010Away, offer a promising alternative for endogenous c\u2010Myc degradation but are limited by ineffective intracellular antibody delivery and uneven endogenous TRIM21 levels in various cancer cells. To overcome these, herein we disclose an acid\u2010responsive nanoplatform using amorphous carbonated calcium phosphate nanoparticles (ACCP NPs) for effective intracellular co\u2010delivery of TRIM21 and antibodies. Under mild biomimetic conditions, TRIM21\u2010antibody complexes were effectively mineralized and encapsulated in the formed nanoparticles. Following endocytic uptake, these acid\u2010sensitive ACCP NPs disassembled in endo\/lysosomes, facilitating subsequent endo\/lysosomal escape and cytosolic cargo release, leading to eventual intracellular TPD. In vitro, mineralized TRIM21\u2010antibody complexes from ACCP NPs effectively degraded various intracellular targets, particularly c\u2010Myc, across diverse cell types, including those that are TRIM21\u2010deficient. Specifically, m\u2010T21\u2010c\u2010Myc Ab nanoparticle degraded c\u2010Myc via the ubiquitin\u2010proteasome system and concurrently reduced MAX levels, synergistically inhibiting c\u2010Myc transcriptional activity. In vivo, m\u2010T21\u2010c\u2010Myc Ab significantly suppressed tumor growth without major organ toxicity. This work establishes ACCP NP\u2010based TPD as a versatile and efficient platform for TRIM21\/antibody\u2010mediated degradation and a promising strategy for targeting other \u201cundruggable\u201d proteins.<\/jats:p>","DOI":"10.1002\/anie.6002660","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T12:02:21Z","timestamp":1787227341000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intracellular Delivery of Antibody\u2010Based Therapeutics for Targeted Oncogenic c\u2010Myc Degradation in Mammalian Cells and Mice"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-3354-9606","authenticated-orcid":false,"given":"Lvyang","family":"Peng","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences Shenzhen Campus of Sun Yat\u2010Sen University  Shenzhen 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