2026-10-13T00:45:32Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34037145 2026-09-30T23:04:11Z category_4 category_7 category_12 category_13 category_14 category_734 category_64 portal_63 item_type_6 month_year_09_2026

Rare-Earth-Coordinated Glutamine Nanostructure-Induced “Pseudo-Overnutrition” Metabolic Therapy Junrong Wang (28268) Mengqian Xu (16324682) Guoqing Zhu (10898589) Shanshan Zhang (50616) Yunlong Li (117641) Ping’an Ma (1524742) Jun Lin (509093) Chunxia Li (182841) Biochemistry Medicine Cell Biology Genetics Molecular Biology Biological Sciences not elsewhere classified Cancer termed “ pseudo subsequently internalized predominantly induced “ pseudo even promote invasion enhancing antigen presentation blocks mtorc1 activation activating antitumor immunity gln preferentially interacts gln disrupts v triggering metabolic collapse rendering cells unable glutamine microenvironment induced coordinated glutamine nanostructure previously unrecognized concept metabolic therapeutic strategy accumulates within lysosomes gln ). therapeutic vulnerability metabolic plasticity metabolic intervention dendritic cells glutamine transporters yet nutrient strong dependency resulting dysfunction progressive accumulation overnutrition ”. overnutrition ” nutrient utilization mechanistic framework leverages rather glucose metabolism effectively utilized confined primarily compensatory mechanisms cell membranes Tumor cells display a strong dependency on nutrients, yet nutrient-deprivation strategies often fail due to their metabolic plasticity and compensatory mechanisms, and can even promote invasion and metastasis. Here, we propose a metabolic therapeutic strategy that leverages rather than suppresses tumor nutrient addiction, termed “pseudo-overnutrition”. This approach induces tumor cells to continuously uptake nutrient analogs that cannot be effectively utilized, thereby decoupling nutrient input from nutrient utilization and triggering metabolic collapse. To validate this concept, we designed and assembled rare-earth–coordinated glutamine nanoparticles (RE-Gln). RE-Gln preferentially interacts with glutamine transporters on tumor-cell membranes, is subsequently internalized predominantly through macropinocytosis, and accumulates within lysosomes. The progressive accumulation of RE-Gln disrupts V-ATPase–dependent lysosomal nutrient sensing and blocks mTORC1 activation, rendering cells unable to effectively utilize nutrients despite continuous uptake. Importantly, the resulting dysfunction is confined primarily to lysosomes, while mitochondrial integrity remains preserved. This lysosome-centered impairment ultimately causes widespread disruption of glutamine and glucose metabolism. Moreover, the high-glutamine microenvironment induced by RE-Gln impairs lysosomal biogenesis and function in dendritic cells, enhancing antigen presentation and activating antitumor immunity. These findings establish “pseudo-overnutrition” as a previously unrecognized concept for metabolic intervention in cancer and provide a mechanistic framework for converting tumor nutrient dependency into a therapeutic vulnerability. 2026-09-30T00:00:00Z Text Journal contribution 10.1021/jacs.6c13842.s001 https://figshare.com/articles/journal_contribution/Rare-Earth-Coordinated_Glutamine_Nanostructure-Induced_Pseudo-Overnutrition_Metabolic_Therapy/34037145 CC BY-NC 4.0