Tumor microenvironment-responsive drug self-delivery systems utilize tumor microenvironment-responsive chemical bonds to link anti-tumor drugs,exploiting the hydrophilic and hydrophobic properties of different drugs t...Tumor microenvironment-responsive drug self-delivery systems utilize tumor microenvironment-responsive chemical bonds to link anti-tumor drugs,exploiting the hydrophilic and hydrophobic properties of different drugs to form amphiphilic prodrug molecules with self-assembly characteristics.Upon stimulation by specific factors in the tumor microenvironment,these amphiphilic prodrug molecules can release drugs at precise sites within the tumor.These strategies significantly increase the drug concentration at the tumor site while effectively reducing the damage of anti-cancer drugs to normal tissues.Owing to the advanced delivery strategies such as synergistic administration and controlled drug release,tumor microenvironment-responsive drug self-delivery systems hold great potential for treating malignant tumors with multidrug resistance(MDR).At the same time,the stimulus-reactivity of metal complexes provides an important opportunity to design site-specific prodrugs that can maximize therapeutic efficacy while minimizing adverse side effects of metal drugs.This innovative drug design complements the tumor microenvironment-responsive self-delivery system,providing more feasible therapeutic strategies and possibilities in the field of cancer therapy and drug delivery.This work provides a comprehensive review of recent advancements in drug self-delivery systems,offering insights into their potential applications in cancer therapy and MDR reversal.展开更多
Iron overload has been evidenced to contribute to obesity-associated metabolic disorders,including insulin resistance.Strategies to reduce iron levels might help manage the metabolic complications associated with obes...Iron overload has been evidenced to contribute to obesity-associated metabolic disorders,including insulin resistance.Strategies to reduce iron levels might help manage the metabolic complications associated with obesity.Here,it is demonstrated that the specific accumulation of oleic acid-modified polyoxovanadates(OPOVs)in adipose tissue leads to the reduction of iron concentrations in adipocytes in mice fed with a high-fat diet(HFD).Conjugation of oleic acids to polyoxovanadates enables tissue-specific depletion of iron from white adipose tissue(WAT)by OPOVs,protecting mice from HFD-induced obesity and obesity-associated metabolic deteriorations.Glucose tolerance and insulin sensitivity are improved in OPOV-treated mice,which demonstrates that the OPOV-induced iron depletion can reverse the metabolic degeneration caused by HFD-induced obesity.Furthermore,a decrease in expression of the marker genes of iron overload suggests the participation of OPOVs in maintaining iron homeostasis and a potential medical application of vanadium clusters in targeting the iron overload caused by obesity.These findings underscore the potential of vanadate-based clusters tailored to address the complex interplay between iron metabolism and metabolic health.展开更多
基金supported by the National Natural Science Foundation of China(No.21907059)Shandong Province Chinese Medicine Science and Technology Development Project(No.M-2022258)+1 种基金the Young Scientist Development Foundation of Shandong First Medical University(No.202201-002)the Academic Promotion Program of Shandong First Medical University(Nos.2019LJ003 and 2019QL011).
文摘Tumor microenvironment-responsive drug self-delivery systems utilize tumor microenvironment-responsive chemical bonds to link anti-tumor drugs,exploiting the hydrophilic and hydrophobic properties of different drugs to form amphiphilic prodrug molecules with self-assembly characteristics.Upon stimulation by specific factors in the tumor microenvironment,these amphiphilic prodrug molecules can release drugs at precise sites within the tumor.These strategies significantly increase the drug concentration at the tumor site while effectively reducing the damage of anti-cancer drugs to normal tissues.Owing to the advanced delivery strategies such as synergistic administration and controlled drug release,tumor microenvironment-responsive drug self-delivery systems hold great potential for treating malignant tumors with multidrug resistance(MDR).At the same time,the stimulus-reactivity of metal complexes provides an important opportunity to design site-specific prodrugs that can maximize therapeutic efficacy while minimizing adverse side effects of metal drugs.This innovative drug design complements the tumor microenvironment-responsive self-delivery system,providing more feasible therapeutic strategies and possibilities in the field of cancer therapy and drug delivery.This work provides a comprehensive review of recent advancements in drug self-delivery systems,offering insights into their potential applications in cancer therapy and MDR reversal.
基金supported by the National Natural Science Foundation of China(No.22101086)Guangzhou Basic and Applied Basic Research Project(No.202201010052)Guangdong Basic and Applied Basic Research Foundation(No.2023A1515140030).
文摘Iron overload has been evidenced to contribute to obesity-associated metabolic disorders,including insulin resistance.Strategies to reduce iron levels might help manage the metabolic complications associated with obesity.Here,it is demonstrated that the specific accumulation of oleic acid-modified polyoxovanadates(OPOVs)in adipose tissue leads to the reduction of iron concentrations in adipocytes in mice fed with a high-fat diet(HFD).Conjugation of oleic acids to polyoxovanadates enables tissue-specific depletion of iron from white adipose tissue(WAT)by OPOVs,protecting mice from HFD-induced obesity and obesity-associated metabolic deteriorations.Glucose tolerance and insulin sensitivity are improved in OPOV-treated mice,which demonstrates that the OPOV-induced iron depletion can reverse the metabolic degeneration caused by HFD-induced obesity.Furthermore,a decrease in expression of the marker genes of iron overload suggests the participation of OPOVs in maintaining iron homeostasis and a potential medical application of vanadium clusters in targeting the iron overload caused by obesity.These findings underscore the potential of vanadate-based clusters tailored to address the complex interplay between iron metabolism and metabolic health.
