Colorectal cancer is a common cancer worldwide.Traditional chemotherapeutic drugs often face limitations such as poor aqueous solubility and high systemic toxicity,which can lead to adverse side effects and limited th...Colorectal cancer is a common cancer worldwide.Traditional chemotherapeutic drugs often face limitations such as poor aqueous solubility and high systemic toxicity,which can lead to adverse side effects and limited therapeutic efficacy.In this study,a library of one kind of biodegradable and biocompatible polymer,leucine based-poly(ester amide)s(Leu-PEAs)was developed and utilized as drug carrier.The structure of Leu-PEAs can be tuned to alter their physicochemical properties,enhancing drug loading capacity and delivery efficiency.Leu-PEAs can self-assemble into nanoparticles by nanoprecipitation and load paclitaxel(PTX)with the diameter of~108 nm and PTX loading capacity of~8.5%.PTX-loaded Leu-PEAs nanoparticles(PTX@Leu-PEAs)demonstrated significant inhibition of CT26 cell growth in vitro.In vivo,these nanoparticles exhibited prolonged tumor accumulation and antitumor effects,with no observed toxicity to normal organs.Furthermore,blank Leu-PEAs nanoparticles also showed antitumor effects in vitro and in vivo,which may be attributed to the activation of the mammalian target of rapamycin(m TOR)pathway by leucine.Consequently,this biocompatible Leu-PEAs nano-drug delivery system shows potential as a promising strategy for colorectal cancer treatment,warranting further investigation.展开更多
Psoriasis is a common chronic inflammatory skin disease driven by the aberrant activation of dendritic cells(DCs)and T cells,ultimately leading to increased production of cytokines such as interleukin(IL)-23 and IL-17...Psoriasis is a common chronic inflammatory skin disease driven by the aberrant activation of dendritic cells(DCs)and T cells,ultimately leading to increased production of cytokines such as interleukin(IL)-23 and IL-17A.It is established that the cGAS-STING pathway is essential for psoriatic inflammation,however,the specific role of cGAS-STING signaling in DCs within this context remains unclear.In this study,we demonstrated the upregulation of cGAS-STING signaling in psoriatic lesions by analyzing samples from both clinical patients and imiquimod(IMQ)-treated mice.Using a conditional Sting-knockout transgenic mouse model,we elucidated the impact of cGAS-STING signaling in DCs on the activation of IL-17-and IFN-γ-producing T cells in psoriatic inflammation.Ablation of the Sting hampers DC activation leads to decreased numbers of IL-17-producing T cells and Th1 cells,and thus subsequently attenuates psoriatic inflammation in the IMQ-induced mouse model.Furthermore,we explored the therapeutic potential of the STING inhibitor C-176,which reduces psoriatic inflammation and enhances the anti-IL-17A therapeutic response.Our results underscore the critical role of cGAS-STING signaling in DCs in driving psoriatic inflammation and highlight a promising psoriasis treatment.展开更多
基金support of the National Natural Science Foundation of China(Nos.52173150,52073313)the Guangzhou Science and Technology Program City-University Joint Funding Project(No.2023A03J0001)the Shenzhen Science and Technology Program(No.KCXFZ 202002011010232)。
文摘Colorectal cancer is a common cancer worldwide.Traditional chemotherapeutic drugs often face limitations such as poor aqueous solubility and high systemic toxicity,which can lead to adverse side effects and limited therapeutic efficacy.In this study,a library of one kind of biodegradable and biocompatible polymer,leucine based-poly(ester amide)s(Leu-PEAs)was developed and utilized as drug carrier.The structure of Leu-PEAs can be tuned to alter their physicochemical properties,enhancing drug loading capacity and delivery efficiency.Leu-PEAs can self-assemble into nanoparticles by nanoprecipitation and load paclitaxel(PTX)with the diameter of~108 nm and PTX loading capacity of~8.5%.PTX-loaded Leu-PEAs nanoparticles(PTX@Leu-PEAs)demonstrated significant inhibition of CT26 cell growth in vitro.In vivo,these nanoparticles exhibited prolonged tumor accumulation and antitumor effects,with no observed toxicity to normal organs.Furthermore,blank Leu-PEAs nanoparticles also showed antitumor effects in vitro and in vivo,which may be attributed to the activation of the mammalian target of rapamycin(m TOR)pathway by leucine.Consequently,this biocompatible Leu-PEAs nano-drug delivery system shows potential as a promising strategy for colorectal cancer treatment,warranting further investigation.
基金supported by China National Natural Science Foundation(grant nos.82374445,82303061,82305233 and 82373179)Shanghai Shuguang Scholar(grant no.22SG42)+3 种基金Scientific research project of Shanghai Municipal Health Commission(grant no.20224Z0019)Key Discipline Construction Project of Shanghai Three Year Action Plan for Strengthening the Construction of Public Health System(grant no.GWVI-11.1-24)High-level Chinese Medicine Key Discipline Construction Project(Integrative Chinese and Western Medicine Clinic)of National Administration of TCM(grant no.zyyzdxk-2023065)Evidence-based dermatology base sponsored by state Administration of Traditional Chinese medicine.
文摘Psoriasis is a common chronic inflammatory skin disease driven by the aberrant activation of dendritic cells(DCs)and T cells,ultimately leading to increased production of cytokines such as interleukin(IL)-23 and IL-17A.It is established that the cGAS-STING pathway is essential for psoriatic inflammation,however,the specific role of cGAS-STING signaling in DCs within this context remains unclear.In this study,we demonstrated the upregulation of cGAS-STING signaling in psoriatic lesions by analyzing samples from both clinical patients and imiquimod(IMQ)-treated mice.Using a conditional Sting-knockout transgenic mouse model,we elucidated the impact of cGAS-STING signaling in DCs on the activation of IL-17-and IFN-γ-producing T cells in psoriatic inflammation.Ablation of the Sting hampers DC activation leads to decreased numbers of IL-17-producing T cells and Th1 cells,and thus subsequently attenuates psoriatic inflammation in the IMQ-induced mouse model.Furthermore,we explored the therapeutic potential of the STING inhibitor C-176,which reduces psoriatic inflammation and enhances the anti-IL-17A therapeutic response.Our results underscore the critical role of cGAS-STING signaling in DCs in driving psoriatic inflammation and highlight a promising psoriasis treatment.
