biostudies-literatureZhao QProject of International Cooperation and Exchanges of the National Natural Science Foundation of ChinaInnovation Group Project of National Natural Science Foundation of ChinaNatural Science Foundation of ShanghaiProjects of Shanghai Science and Technology CommissionNational Key Research and Development Program of China717https://www.ebi.ac.uk/biostudies/studies/S-EPMC12625341biostudies-literatureUnknown23(1)This work explores how Autocrine Motility Factor Receptor (AMFR)-driven ubiquitination of Family with Sequence Similarity 134 Member B (FAM134B) in hypoxia adaptation and endoplasmic reticulum-selective autophagy (ER-phagy) in osteosarcoma (OS), aiming to develop a stimuli-responsive nanoplatform (S-SNACs@TPZ@Cas-A) for targeted therapy. Transcriptomic analysis identifies the AMFR-FAM134B axis as crucial for OS survival under hypoxic conditions. The nanoplatform, thoroughly characterized via established methods, co-delivers CRISPR-Cas9 RNP and tirapazamine to disrupt AMFR and enhance reactive oxygen species production, inhibiting tumor growth in mouse models. In vitro assays confirm decreased FAM134B ubiquitination and ER-phagy inhibition. In vivo, S-SNACs@TPZ@Cas-A reduces tumor volume, mJournal of nanobiotechnologyAMFR-mediated ER-phagy regulation and therapeutic targeting in osteosarcoma: a multifunctional nanoplatform strategy.PMC126253418202010801722ZR146760021DZ2203200, 20142201300819210022017FYA0205301Lou QYang GLi JLu XRen ZZhu BLiu ZZhao QXu TGao ZWang WPeng LYu ZCui DSong ZZhao HJesus M FfalseAMFR-mediated ER-phagy regulation and therapeutic targeting in osteosarcoma: a multifunctional nanoplatform strategy.This work explores how Autocrine Motility Factor Receptor (AMFR)-driven ubiquitination of Family with Sequence Similarity 134 Member B (FAM134B) in hypoxia adaptation and endoplasmic reticulum-selective autophagy (ER-phagy) in osteosarcoma (OS), aiming to develop a stimuli-responsive nanoplatform (S-SNACs@TPZ@Cas-A) for targeted therapy. Transcriptomic analysis identifies the AMFR-FAM134B axis as crucial for OS survival under hypoxic conditions. The nanoplatform, thoroughly characterized via established methods, co-delivers CRISPR-Cas9 RNP and tirapazamine to disrupt AMFR and enhance reactive oxygen species production, inhibiting tumor growth in mouse models. In vitro assays confirm decreased FAM134B ubiquitination and ER-phagy inhibition. In vivo, S-SNACs@TPZ@Cas-A reduces tumor volume, m2025-01-01T00:00:00Z2025 Nov2026-06-05T15:58:51.653Z2026-06-05T03:06:50.05ZS-EPMC126253414125020610.1186/s12951-025-03754-8