Although transcatheter arterial chemo-embolization(TACE)plays a key role on clinical treatment of hepatocellular carcinoma(HCC),it was greatly limited by the poor synergistic effect between chemotherapeutics and physi...Although transcatheter arterial chemo-embolization(TACE)plays a key role on clinical treatment of hepatocellular carcinoma(HCC),it was greatly limited by the poor synergistic effect between chemotherapeutics and physical embolization to tumor-feeding arteries.In the present work,a temperature sensitive polymer poly(N-isopropylacrylamide-b-methacrylic acid)(PNA),which was modified with gold nanoparticles(AuNP@PNA),was successfully used to encapsulate doxorubicin(DOX)by electrostatic binding with their carboxyl groups.The resultant gold nanomedicines(AuNP@PNA/DOX)exhibited temperature responsive sol-gel phase transition,favorable shear thinning effect and X-ray angiography.By in vivo evaluation of vascular embolization on VX2-tumor-bearing rabbits,AuNP@PNA/DOX exhibited far better antitumor efficacy than Lipiodol/DOX,on either tumor growth inhibition,proliferation,apoptosis,necrosis or anti-metastasis.Owing to sufficient embolization to tumor vascular networks,AuNP@PNA/DOX down-regulated the expression levels of HIF-1α,VEGF and MMP-9,and prompted more efficient activation on CD3+/CD8+T cells and the related cytokines,suggesting the synergistic effect between AuNP@PNA and DOX on the improvement of post-operative tumor immunosuppressive microenvironment.With their favorable pharmcokinetics and biocompatibility,AuNP@PNA/DOX is promising to be developed as a multi-functional artery-imaging/embolic agent with immune-chemo-embolization for enhancing TACE efficacy on HCC.展开更多
Precise nanomedicine has been extensively explored for efficient cancer imaging and targeted cancer therapy, as evidenced by a few breakthroughs in their preclinical and clinical explorations. Here, we demonstrate the...Precise nanomedicine has been extensively explored for efficient cancer imaging and targeted cancer therapy, as evidenced by a few breakthroughs in their preclinical and clinical explorations. Here, we demonstrate the recent advances of intelligent cancer nanomedicine, and discuss the comprehensive understanding of their structure-function relationship for smart and efficient cancer nanomedicine including various imaging and therapeutic applications, as well as nanotoxicity. In particular, a few emerging strategies that have advanced cancer nanomedicine are also highlighted as the emerging focus such as tumor imprisonment, supramolecular chemotherapy, and DNA nanorobot. The challenge and outlook of some scientific and engineering issues are also discussed in future development. We wish to highlight these new progress of precise nanomedicine with the ultimate goal to inspire more successful explorations of intelligent nanoparticles for future clinical translations.展开更多
基金supported by the National Basic Research Program of China(Nos.2020YFA0710700 and 2018YFA0208900)the National Natural Science Foundation of China(Nos.82172758,81873919,and 81801810).
文摘Although transcatheter arterial chemo-embolization(TACE)plays a key role on clinical treatment of hepatocellular carcinoma(HCC),it was greatly limited by the poor synergistic effect between chemotherapeutics and physical embolization to tumor-feeding arteries.In the present work,a temperature sensitive polymer poly(N-isopropylacrylamide-b-methacrylic acid)(PNA),which was modified with gold nanoparticles(AuNP@PNA),was successfully used to encapsulate doxorubicin(DOX)by electrostatic binding with their carboxyl groups.The resultant gold nanomedicines(AuNP@PNA/DOX)exhibited temperature responsive sol-gel phase transition,favorable shear thinning effect and X-ray angiography.By in vivo evaluation of vascular embolization on VX2-tumor-bearing rabbits,AuNP@PNA/DOX exhibited far better antitumor efficacy than Lipiodol/DOX,on either tumor growth inhibition,proliferation,apoptosis,necrosis or anti-metastasis.Owing to sufficient embolization to tumor vascular networks,AuNP@PNA/DOX down-regulated the expression levels of HIF-1α,VEGF and MMP-9,and prompted more efficient activation on CD3+/CD8+T cells and the related cytokines,suggesting the synergistic effect between AuNP@PNA and DOX on the improvement of post-operative tumor immunosuppressive microenvironment.With their favorable pharmcokinetics and biocompatibility,AuNP@PNA/DOX is promising to be developed as a multi-functional artery-imaging/embolic agent with immune-chemo-embolization for enhancing TACE efficacy on HCC.
基金supported by the National Natural Science Foundation of China (11621505, 11435002, 31671016)
文摘Precise nanomedicine has been extensively explored for efficient cancer imaging and targeted cancer therapy, as evidenced by a few breakthroughs in their preclinical and clinical explorations. Here, we demonstrate the recent advances of intelligent cancer nanomedicine, and discuss the comprehensive understanding of their structure-function relationship for smart and efficient cancer nanomedicine including various imaging and therapeutic applications, as well as nanotoxicity. In particular, a few emerging strategies that have advanced cancer nanomedicine are also highlighted as the emerging focus such as tumor imprisonment, supramolecular chemotherapy, and DNA nanorobot. The challenge and outlook of some scientific and engineering issues are also discussed in future development. We wish to highlight these new progress of precise nanomedicine with the ultimate goal to inspire more successful explorations of intelligent nanoparticles for future clinical translations.
