Activated pancreatic stellate cells(PSCs)are the main source of collagen layer deposition and the key target in pancreatic fibrosis.However,no effective treatment specific to pancreatic fibrosis clinically,owing to th...Activated pancreatic stellate cells(PSCs)are the main source of collagen layer deposition and the key target in pancreatic fibrosis.However,no effective treatment specific to pancreatic fibrosis clinically,owing to the drug accumulation blocked by the collagen barrier and thus it is difficult to inhibit activated PSCs precisely.Herein,a PSCs-targeting nano-system based on“nanodrill”strategy(LA-PC)was designed to enhance the accumulation of all-trans retinoic acid(ATRA)in PSCs,relying on the platelet-derived growth factor receptor beta(PDGFRβ)-targeting peptide(p PB:C*SRNLIDC*)and collagenase(Col).After being injected into fibrotic mice via tail vein,the Col modified on LA-PC can remove the excess collagen layer,and the drug delivery efficiency through pPB targeting peptide was more than 5 times higher than that of free ATRA,as well as the degree of fibrosis significantly reduced.Notably,this nano-system effectively inhibited platelet-derived growth factor subunit B(PDGF-BB)/PDGFRβaxis on PSCs via a down-regulated extracellular signal-regulated protein kinase(ERK)pathway,and accordingly reduced the level of PDGFBB.Thus,the smart platform provided a promising strategy for the treatment of pancreatic fibrosis to achieve the precise regulation of PSCs.展开更多
Circulating tumor cells(CTCs)significantly impact the overall survival and progression-free survival of cancer patients.However,the current strategies for CTC separation and enrichment are limited as they analyze only...Circulating tumor cells(CTCs)significantly impact the overall survival and progression-free survival of cancer patients.However,the current strategies for CTC separation and enrichment are limited as they analyze only small-volume blood samples,which is insufficient to comprehensively profile the distribution of CTCs in the blood and eliminate them.To address this issue,we developed a peripheral blood CTC removal device(PBCRD)inspired by hemoperfusion.It comprises systems for CTCcapturing and returning purified blood into circulation.The CTC capturing system consists of antibody-modified functional microspheres(AFMPs),while the purified blood returning system includes a peristaltic circulation pump for clinical blood perfusion and catheters.The PBCRD can efficiently capture,enrich,and remove CTCs from peripheral circulation in real-time,effectively inhibiting their biodistribution.The high biocompatibility of AFMPs ensures that PBCRD is safe and does not cause injuries.Overall,this work provides a new class of ideas for the effective capture and removal of CTCs from the peripheral circulation,which is expected to be an effective strategy to assist in the clinical treatment of tumors and inhibit metastasis.展开更多
基金financially supported by the National Natural Science Foundation of China(Nos.82020108029,82073398)the National Key Research and Development Program of China(No.2022YFE0198400)supported by Double FirstRate construction plan of China Pharmaceutical University(No.CPU2022QZ18)。
文摘Activated pancreatic stellate cells(PSCs)are the main source of collagen layer deposition and the key target in pancreatic fibrosis.However,no effective treatment specific to pancreatic fibrosis clinically,owing to the drug accumulation blocked by the collagen barrier and thus it is difficult to inhibit activated PSCs precisely.Herein,a PSCs-targeting nano-system based on“nanodrill”strategy(LA-PC)was designed to enhance the accumulation of all-trans retinoic acid(ATRA)in PSCs,relying on the platelet-derived growth factor receptor beta(PDGFRβ)-targeting peptide(p PB:C*SRNLIDC*)and collagenase(Col).After being injected into fibrotic mice via tail vein,the Col modified on LA-PC can remove the excess collagen layer,and the drug delivery efficiency through pPB targeting peptide was more than 5 times higher than that of free ATRA,as well as the degree of fibrosis significantly reduced.Notably,this nano-system effectively inhibited platelet-derived growth factor subunit B(PDGF-BB)/PDGFRβaxis on PSCs via a down-regulated extracellular signal-regulated protein kinase(ERK)pathway,and accordingly reduced the level of PDGFBB.Thus,the smart platform provided a promising strategy for the treatment of pancreatic fibrosis to achieve the precise regulation of PSCs.
基金supported by the National Natural Science Foundation of China(82020108029,82473867,82302367,82304416)supported by the Natural Science Foundation of Jiangsu Province(BK20231016,BK20231019)+3 种基金the Natural Science Foundation of Jiangsu Basic Research Program-Project jointly funded by province and city(BK20232035)State Key Laboratory of Natural Medicines China Pharmaceutical University(SKLNMZZ202021)Double First-class University Projects(CPU2018GY06)Double First-Rate construction plan of China Pharmaceutical University(CPU2022QZ18).
文摘Circulating tumor cells(CTCs)significantly impact the overall survival and progression-free survival of cancer patients.However,the current strategies for CTC separation and enrichment are limited as they analyze only small-volume blood samples,which is insufficient to comprehensively profile the distribution of CTCs in the blood and eliminate them.To address this issue,we developed a peripheral blood CTC removal device(PBCRD)inspired by hemoperfusion.It comprises systems for CTCcapturing and returning purified blood into circulation.The CTC capturing system consists of antibody-modified functional microspheres(AFMPs),while the purified blood returning system includes a peristaltic circulation pump for clinical blood perfusion and catheters.The PBCRD can efficiently capture,enrich,and remove CTCs from peripheral circulation in real-time,effectively inhibiting their biodistribution.The high biocompatibility of AFMPs ensures that PBCRD is safe and does not cause injuries.Overall,this work provides a new class of ideas for the effective capture and removal of CTCs from the peripheral circulation,which is expected to be an effective strategy to assist in the clinical treatment of tumors and inhibit metastasis.
