Conventional drug-delivery systems(DDSs)for oncology often face challenges such as insufficient tumor selectivity,rapid systemic clearance,limited penetration across stromal and immune barriers,and suboptimal biocompa...Conventional drug-delivery systems(DDSs)for oncology often face challenges such as insufficient tumor selectivity,rapid systemic clearance,limited penetration across stromal and immune barriers,and suboptimal biocompatibility.Live immune cell-based drug-delivery systems(LCDDSs)overcome these limitations by exploiting the innate tumor-homing capacity,high biocompatibility,and dynamic tumor microenvironment(TME)interactions intrinsic to leukocytes,facilitating precise targeting with minimal systemic toxicity.Furthermore,immune cells act as“mobile microprocessors”,actively converting precursor payloads into therapeutically functional cargos at the tumor site and dynamically reshaping the TME.Nonetheless,the clinical translation of LCDDSs remains impeded by limited drug-loading capacities,premature payload degradation,potential impairment of immune-cell function,and insufficient persistence in immunosuppressive environments.To overcome these hurdles,immune cell reprogramming via genetic,metabolic,or epigenetic modifications emerges as a promising strategy.Such interventions improve cellular fitness,enhance tumor infiltration,augment payload transport efficiency,confer programmable release profiles,mitigate cellular exhaustion,and increase adaptability to the hostile TME.This review systemically evaluates how immune cell reprogramming advances LCDDSs by examining mechanistic benefits,drug compatibility considerations,payload loading strategies,and design criteria essential for achieving clinical controllability,safety,and scalability.By integrating immune-cell engineering with cutting-edge drug delivery technologies,reprogrammed LCDDSs represent a versatile and powerful platform for next-generation precision oncology therapeutics.展开更多
Cuproptosis,a recently discovered form of regulated cell death involving copper ion metabolism,has emerged as a promising approach for tumor therapy.This pathway not only directly eliminates tumor cells but also promo...Cuproptosis,a recently discovered form of regulated cell death involving copper ion metabolism,has emerged as a promising approach for tumor therapy.This pathway not only directly eliminates tumor cells but also promotes immunogenic cell death(ICD),reshaping the tumor microenvironment(TME)and initiating robust anti-tumor immune responses.However,translating cuproptosis-based therapies into clinical applications is hindered by challenges,including complex metabolic regulation,TME heterogeneity,and the precision required for effective drug delivery.To address these limitations,nanoparticles offer transformative solutions by providing precise delivery of cuproptosis-inducing agents,controlled drug release,and enhanced therapeutic efficacy through simultaneous modulation of metabolic pathways and immune responses.This review systematically discusses recent advancements in nanoparticle-based cuproptosis delivery systems,highlighting nanoparticle design principles and their synergistic effects when integrated with other therapeutic modalities such as ICB,PTT,and CDT.Furthermore,we explore the potential of cuproptosis-based nanomedicine for personalized cancer treatment by emphasizing strategies for TME stratification and therapeutic optimization tailored to patient profiles.By integrating current insights from metabolic reprogramming,tumor immunotherapy,and nanotechnology,this review aims to facilitate the clinical translation of cuproptosis nanomedicine and significantly contribute to the advancement of precision oncology.展开更多
基金funded by the National Natural Science Foundation of China(No.82374050).
文摘Conventional drug-delivery systems(DDSs)for oncology often face challenges such as insufficient tumor selectivity,rapid systemic clearance,limited penetration across stromal and immune barriers,and suboptimal biocompatibility.Live immune cell-based drug-delivery systems(LCDDSs)overcome these limitations by exploiting the innate tumor-homing capacity,high biocompatibility,and dynamic tumor microenvironment(TME)interactions intrinsic to leukocytes,facilitating precise targeting with minimal systemic toxicity.Furthermore,immune cells act as“mobile microprocessors”,actively converting precursor payloads into therapeutically functional cargos at the tumor site and dynamically reshaping the TME.Nonetheless,the clinical translation of LCDDSs remains impeded by limited drug-loading capacities,premature payload degradation,potential impairment of immune-cell function,and insufficient persistence in immunosuppressive environments.To overcome these hurdles,immune cell reprogramming via genetic,metabolic,or epigenetic modifications emerges as a promising strategy.Such interventions improve cellular fitness,enhance tumor infiltration,augment payload transport efficiency,confer programmable release profiles,mitigate cellular exhaustion,and increase adaptability to the hostile TME.This review systemically evaluates how immune cell reprogramming advances LCDDSs by examining mechanistic benefits,drug compatibility considerations,payload loading strategies,and design criteria essential for achieving clinical controllability,safety,and scalability.By integrating immune-cell engineering with cutting-edge drug delivery technologies,reprogrammed LCDDSs represent a versatile and powerful platform for next-generation precision oncology therapeutics.
基金supported by the National Natural Science Foundation of China(Grant Nos.82374050 and 82074030)the Faculty Development Research Project of Tianjin University of Traditional Chinese Medicine(Project No.Y-202506,China)the Open Projects Fund of the Shandong Key Laboratory of Carbohydrate Chemistry and Glycobiology,Shandong University(Grant No.2023CCG13,China).
文摘Cuproptosis,a recently discovered form of regulated cell death involving copper ion metabolism,has emerged as a promising approach for tumor therapy.This pathway not only directly eliminates tumor cells but also promotes immunogenic cell death(ICD),reshaping the tumor microenvironment(TME)and initiating robust anti-tumor immune responses.However,translating cuproptosis-based therapies into clinical applications is hindered by challenges,including complex metabolic regulation,TME heterogeneity,and the precision required for effective drug delivery.To address these limitations,nanoparticles offer transformative solutions by providing precise delivery of cuproptosis-inducing agents,controlled drug release,and enhanced therapeutic efficacy through simultaneous modulation of metabolic pathways and immune responses.This review systematically discusses recent advancements in nanoparticle-based cuproptosis delivery systems,highlighting nanoparticle design principles and their synergistic effects when integrated with other therapeutic modalities such as ICB,PTT,and CDT.Furthermore,we explore the potential of cuproptosis-based nanomedicine for personalized cancer treatment by emphasizing strategies for TME stratification and therapeutic optimization tailored to patient profiles.By integrating current insights from metabolic reprogramming,tumor immunotherapy,and nanotechnology,this review aims to facilitate the clinical translation of cuproptosis nanomedicine and significantly contribute to the advancement of precision oncology.
