Traditional surgical treatment is difficult to thoroughly remove esophageal squamous cell carcinomas(ESCC),postoperative recurrence caused by residual tumor cells is a critical factor in the poor prognosis.Since surgi...Traditional surgical treatment is difficult to thoroughly remove esophageal squamous cell carcinomas(ESCC),postoperative recurrence caused by residual tumor cells is a critical factor in the poor prognosis.Since surgical resection promotes the local angiogenesis at the tumor site,further exacerbating the proliferation and invasion of residual tumor cells,it is urgent to inhibit angiogenesis after surgery.Here,a functional peptide-based nanomedicine was obtained from peptide–drug conjugates,which are composed of a hydrophilic targeting motif(vascular endothelial growth factor family and their receptors(VEGFR)targeting peptide for anti-angiogenesis),an ester-linked hydrophobic oridonin(ORI).The nanomedicine exhibits esterase-catalyzed disassembly and drug release,significantly enhanced the anti-tumor efficacy of chemotherapeutics in a postoperative tumor recurrence model through synergistic anti-angiogenic strategies.This study provides an integrated solution for anti-angiogenesisaugmented chemotherapy and demonstrates the encouraging potential for postoperative treatment.展开更多
Photodynamic therapy(PDT)has emerged as an alternative treatment strategy for esophageal squamous cell carcinoma(ESCC).However,the clinical therapeutic efficiency of PDT is severely limited by poorly targeted photosen...Photodynamic therapy(PDT)has emerged as an alternative treatment strategy for esophageal squamous cell carcinoma(ESCC).However,the clinical therapeutic efficiency of PDT is severely limited by poorly targeted photosensitizer delivery,insufficient oxygen supply,and neutralization by excessive glutathione(GSH)in tumor tissue.Herein,an engineered multifunctional thylakoid nanostructure,TMEM@PLGA@GA(abbreviated as TEPG),composed of a thylakoid membrane(TM)and ESCC cell membrane(EM)-fused biomembrane(TM-EM)shell and gambogic acid(GA)-loaded poly(lactic-co-glycolic acid)nanocore,was designed for enhanced PDT for ESCC.When fused with EM,TM-EM exhibits a tumor targeting advantage due to the homologous affinity of tumor membrane camouflage.The catalase present on TM-EM catalytically decomposes endogenous hydrogen peroxide into oxygen to alleviate hypoxia in the tumor tissue.Moreover,when TEPG was selectively internalized by ESCC cells,GA was released to consume the excessive intracellular GSH.Under infrared irradiation,the PDT effects were enhanced by the self-oxygen supply and GSH scavenging ability provided by TEPG.An in vivo study showed that TEPG effectively induced ESCC tumor cell apoptosis and greatly inhibited the growth of ESCC tumors under infrared irradiation.This study constructed an engineered multifunctional thylakoid-based nanomedicine as an integrated solution to enhance PDT for ESCC.展开更多
基金the National Natural Science Foundation of China(Nos.32000998 and U2004123)the Young Elite Scientists Sponsorship Program by Henan Association for Science and Technology(No.2022HYTP046)the China Postdoctoral Science Foundation(Nos.2019TQ0285,2019M662513,2021TQ0298,and 2022TQ0296).
文摘Traditional surgical treatment is difficult to thoroughly remove esophageal squamous cell carcinomas(ESCC),postoperative recurrence caused by residual tumor cells is a critical factor in the poor prognosis.Since surgical resection promotes the local angiogenesis at the tumor site,further exacerbating the proliferation and invasion of residual tumor cells,it is urgent to inhibit angiogenesis after surgery.Here,a functional peptide-based nanomedicine was obtained from peptide–drug conjugates,which are composed of a hydrophilic targeting motif(vascular endothelial growth factor family and their receptors(VEGFR)targeting peptide for anti-angiogenesis),an ester-linked hydrophobic oridonin(ORI).The nanomedicine exhibits esterase-catalyzed disassembly and drug release,significantly enhanced the anti-tumor efficacy of chemotherapeutics in a postoperative tumor recurrence model through synergistic anti-angiogenic strategies.This study provides an integrated solution for anti-angiogenesisaugmented chemotherapy and demonstrates the encouraging potential for postoperative treatment.
基金supported by grants from the National Basic Research Plan of China(grant no.2018YFA0208900)the National Natural Science Foundation of China(grant nos.32000998,32000996,,U2004123)+1 种基金The Young Elite Scientists Sponsorship Program by Henan Association for Science and Technology(grant no.2022HYTP046)the China Postdoctoral Science Foundation(grant nos.2019TQ0285,2019M662513,2020M682358,2020TQ0280,2021TQ0298).
文摘Photodynamic therapy(PDT)has emerged as an alternative treatment strategy for esophageal squamous cell carcinoma(ESCC).However,the clinical therapeutic efficiency of PDT is severely limited by poorly targeted photosensitizer delivery,insufficient oxygen supply,and neutralization by excessive glutathione(GSH)in tumor tissue.Herein,an engineered multifunctional thylakoid nanostructure,TMEM@PLGA@GA(abbreviated as TEPG),composed of a thylakoid membrane(TM)and ESCC cell membrane(EM)-fused biomembrane(TM-EM)shell and gambogic acid(GA)-loaded poly(lactic-co-glycolic acid)nanocore,was designed for enhanced PDT for ESCC.When fused with EM,TM-EM exhibits a tumor targeting advantage due to the homologous affinity of tumor membrane camouflage.The catalase present on TM-EM catalytically decomposes endogenous hydrogen peroxide into oxygen to alleviate hypoxia in the tumor tissue.Moreover,when TEPG was selectively internalized by ESCC cells,GA was released to consume the excessive intracellular GSH.Under infrared irradiation,the PDT effects were enhanced by the self-oxygen supply and GSH scavenging ability provided by TEPG.An in vivo study showed that TEPG effectively induced ESCC tumor cell apoptosis and greatly inhibited the growth of ESCC tumors under infrared irradiation.This study constructed an engineered multifunctional thylakoid-based nanomedicine as an integrated solution to enhance PDT for ESCC.