Lactate oxidase-integrated nanomaterials for tumor microenvironment modulation:Mechanisms and therapeutic applicationsOA
The tumor microenvironment(TME)is dynamically remodeled by metabolic reprogramming,establishing lactate as a central orchestrator of immune evasion through acidosis,CD8^(+)T cell suppression,and epigenetic regulation.While lactate oxidase(LOX)offers therapeutic potential by converting lactate to immunomodulatory H_(2)O_(2),its clinical translation faces critical barriers including enzymatic instability,systemic toxicity,and paradoxical pro-tumorigenic effects.To overcome these limitations,advanced LOX-integrated nanoplatforms employ two synergistic engineering strategies:stimuli-responsive carriers exploit pathological cues(pH,redox gradients,lactate concentration)for spatiotemporally controlled enzyme activation,while biomimetic modifications leverage cell membrane coatings to enhance tumor penetration and homologous targeting.These approaches collectively optimize catalytic stability,prolong intratumoral retention,and minimize off-target effects.By synchronizing lactate depletion with TME dynamics,LOX nanotherapeutics reverse immunosuppressive circuits—restoring effector T cell function,repolarizing protumoral immune cells,and synergizing with checkpoint inhibitors.The concomitant H_(2)O_(2)generation further amplifies metal-catalyzed oxidative damage within therapeutic thresholds.Future development requires AI-optimized carrier design,scalable manufacturing,and enhanced biomimetic penetration strategies to address tumor heterogeneity.Through interdisciplinary integration of materials science and immunometabolism,LOX-based nanoplatforms represent a paradigm-shifting approach to overcoming treatment resistance by concurrently targeting metabolic dysregulation,physical barriers,and immune evasion in solid tumors.
Xiaoxuan Xu;Di Chang;Yu Cai;Jue Wang;Jinqiang Liu;Peirong Xu;Yuanyuan Ma
Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging&Interventional Radiology,Department of Radiology,Zhongda Hospital,Medical School of Southeast University,87 DingJiaQiao Road,Nanjing,Jiangsu 210009,ChinaNurturing Center of Jiangsu Province for State Laboratory of AI Imaging&Interventional Radiology,Department of Radiology,Zhongda Hospital,Medical School of Southeast University,87 DingJiaQiao Road,Nanjing,Jiangsu 210009,ChinaNurturing Center of Jiangsu Province for State Laboratory of AI Imaging&Interventional Radiology,Department of Radiology,Zhongda Hospital,Medical School of Southeast University,87 DingJiaQiao Road,Nanjing,Jiangsu 210009,ChinaNurturing Center of Jiangsu Province for State Laboratory of AI Imaging&Interventional Radiology,Department of Radiology,Zhongda Hospital,Medical School of Southeast University,87 DingJiaQiao Road,Nanjing,Jiangsu 210009,ChinaNurturing Center of Jiangsu Province for State Laboratory of AI Imaging&Interventional Radiology,Department of Radiology,Zhongda Hospital,Medical School of Southeast University,87 DingJiaQiao Road,Nanjing,Jiangsu 210009,ChinaMedical School of Southeast University,87 DingJiaQiao Road,Nanjing,Jiangsu 210009,ChinaNurturing Center of Jiangsu Province for State Laboratory of AI Imaging&Interventional Radiology,Department of Radiology,Zhongda Hospital,Medical School of Southeast University,87 DingJiaQiao Road,Nanjing,Jiangsu 210009,China
通用工业技术
Lactate oxidaseNanomaterialTumor microenvironmentTherapeutic application
《Nano Biomedicine & Engineering》 2026 (1)
P.66-80,15
financially supported by the National Natural Science Foundation of China(NSFC,Nos.82302273,82402355,82372024,82472043)the Natural Science Foundation of Jiangsu Province(BK20230839)
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