This work details a newly developed“sandwich”nanoplatform via neutravidin-biotin system for the detection and treatment of inflammation.First,biotinylated-and folate-conjugated optical imaging micelles targeted acti...This work details a newly developed“sandwich”nanoplatform via neutravidin-biotin system for the detection and treatment of inflammation.First,biotinylated-and folate-conjugated optical imaging micelles targeted activated macrophages via folate/folate receptor interactions.Second,multivalent neutravidin proteins in an optimal concentration accumulated on the biotinylated macrophages.Finally,biotinylated anti-inflammatory drug-loaded micelles delivered drugs effectively at the inflammatory sites via a highly specific neutravidin-biotin affinity.Both in vitro and in vivo studies have shown that the“sandwich”pretargeting platform was able to diagnose inflammation by targeting activated macrophages as well as improve the therapeutic efficacy by amplifying the drug delivery to the inflamed tissue.The overall results support that our new pretargeting platform has the potential for inflammatory disease diagnosis and treatment.展开更多
A fraction of the OA patient population is affected by post-traumatic osteoarthritis(PTOA)following acute joint injuries.Stopping or reversing the progression of PTOA following joint injury could improve long-term fun...A fraction of the OA patient population is affected by post-traumatic osteoarthritis(PTOA)following acute joint injuries.Stopping or reversing the progression of PTOA following joint injury could improve long-term functional outcomes,reduced disability,and medical costs.To more effectively treat articular cartilage injury,we have developed a novel cell-based therapy that involves the pretargeting of apoptotic chondrocytes and the delivery of healthy,metabolically active chondrocytes using click chemistry.Specifically,a pre-targeting agent was prepared via conjugating apoptotic binding peptide(ApoPep-1)and trans-cyclooctene(TCO)onto polyethylene glycol(PEG)polymer carrier.The pre-targeting agent would be introduced to injured areas of articular cartilage,leading to the accumulation of TCO groups on the injured areas from actively binding to apoptotic chondrocytes.Subsequently,methyltetrazine(Tz)-bearing chondrocytes would be immobilized on the surface of TCO-coated injured cartilage via Tz-TCO click chemistry reaction.Using an ex vivo human cartilage explant PTOA model,the effectiveness of this new approach was evaluated.Our studies show that this novel approach(Tz-TCO click chemistry)significantly enhanced the immobilization of healthy and metabolically active chondrocytes to the areas of apoptotic chondrocytes.Histological analyses demonstrated that this treatment regimen would significantly reduce the area of cartilage degeneration and enhance ECM regeneration.The results support that Tz-TCO click chemistry-mediated cell delivery approach has great potential in clinical applications for targeting and treatment of cartilage injury.展开更多
文摘This work details a newly developed“sandwich”nanoplatform via neutravidin-biotin system for the detection and treatment of inflammation.First,biotinylated-and folate-conjugated optical imaging micelles targeted activated macrophages via folate/folate receptor interactions.Second,multivalent neutravidin proteins in an optimal concentration accumulated on the biotinylated macrophages.Finally,biotinylated anti-inflammatory drug-loaded micelles delivered drugs effectively at the inflammatory sites via a highly specific neutravidin-biotin affinity.Both in vitro and in vivo studies have shown that the“sandwich”pretargeting platform was able to diagnose inflammation by targeting activated macrophages as well as improve the therapeutic efficacy by amplifying the drug delivery to the inflamed tissue.The overall results support that our new pretargeting platform has the potential for inflammatory disease diagnosis and treatment.
基金This work was partially supported by UTA Research&Scholarship Excellence GiftThe authors acknowledge the financial support from the National Heart,Lung,and Blood Institute[NIH T32 HL134613 to C.C.]The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
文摘A fraction of the OA patient population is affected by post-traumatic osteoarthritis(PTOA)following acute joint injuries.Stopping or reversing the progression of PTOA following joint injury could improve long-term functional outcomes,reduced disability,and medical costs.To more effectively treat articular cartilage injury,we have developed a novel cell-based therapy that involves the pretargeting of apoptotic chondrocytes and the delivery of healthy,metabolically active chondrocytes using click chemistry.Specifically,a pre-targeting agent was prepared via conjugating apoptotic binding peptide(ApoPep-1)and trans-cyclooctene(TCO)onto polyethylene glycol(PEG)polymer carrier.The pre-targeting agent would be introduced to injured areas of articular cartilage,leading to the accumulation of TCO groups on the injured areas from actively binding to apoptotic chondrocytes.Subsequently,methyltetrazine(Tz)-bearing chondrocytes would be immobilized on the surface of TCO-coated injured cartilage via Tz-TCO click chemistry reaction.Using an ex vivo human cartilage explant PTOA model,the effectiveness of this new approach was evaluated.Our studies show that this novel approach(Tz-TCO click chemistry)significantly enhanced the immobilization of healthy and metabolically active chondrocytes to the areas of apoptotic chondrocytes.Histological analyses demonstrated that this treatment regimen would significantly reduce the area of cartilage degeneration and enhance ECM regeneration.The results support that Tz-TCO click chemistry-mediated cell delivery approach has great potential in clinical applications for targeting and treatment of cartilage injury.
