The key to improve the therapeutic efficacy for cancer treatment is to increase the delivery of drugs to tumors.For this purpose, tumor-microenvironment stimuliresponsive materials have great potential. Here, we prepa...The key to improve the therapeutic efficacy for cancer treatment is to increase the delivery of drugs to tumors.For this purpose, tumor-microenvironment stimuliresponsive materials have great potential. Here, we prepared a new nanomedicine by bonding the conjugate of honokiol(HNK) and 5,6-dimethylxanthenone-4-acetic acid(DMXAA)to a glutathione(GSH)-responsive nanocarrier, poly(α-lipoic acid) polyethylene glycol. The nanomedicine would disintegrate due to the high level of GSH at the tumor sites,achieving the co-delivery of HNK and DMXAA, and realizing the combination therapy through close-range killing by HNK and long-range striking by DMXAA together. In a murine 4T1 breast tumor model, this strategy exhibited high tumor inhibition rate of 93%, and provided a valuable therapeutic choice for cancer therapy.展开更多
Hypoxia is a hallmark of solid tumors,and it significantly impairs the overall anticancer efficacy,particularly photodynamic therapy(PDT).Herein,a catalase-like nanovesicle with near-infrared light-responsiveness,that...Hypoxia is a hallmark of solid tumors,and it significantly impairs the overall anticancer efficacy,particularly photodynamic therapy(PDT).Herein,a catalase-like nanovesicle with near-infrared light-responsiveness,that is,platinum/gold nanoshell encapsulated chlorin e6(Ce6)/resveratrol(Res)liposome(Pt@Au-Ce6/Res-Lip),was developed to surmount this intractable issue.The Pt@Au-Ce6/Res-Lip can decompose overexpressed H_(2)O_(2)in tumor microenvironment to produce vast amounts of O_(2)for further enhancement of the PDT.Under the 808 nm laser irradiation,the Au nanoshells induced hyperthermia at the lesion site to ablate tumor cells,simultaneously inducing the controlled release of photosensitizer Ce6 and chemotherapeutic agent Res.Moreover,stimulated by 660 nm laser,numerous reactive oxygen species were formed to induce apoptosis and necrosis of tumor cells.With the cascade of trimodal therapeutic modality options(chemotherapy,photothermal therapy,and PDT),the Pt@Au-Ce6/Res-Lip showed ultrahigh tumor inhabitation rate in in vitro and in vivo studies,signifying that the Pt@AuCe6/Res-Lip nanovesicle is a promising candidate for effective cancer therapy.展开更多
Many conventional chemotherapeutics play an immune-modulating effect by inducing immunogenic cell death(ICD)in tumor cells.However,they hardly arouse strong antitumor immune response because the immunosuppressive lymp...Many conventional chemotherapeutics play an immune-modulating effect by inducing immunogenic cell death(ICD)in tumor cells.However,they hardly arouse strong antitumor immune response because the immunosuppressive lymphocytes are present in the tumor microenvironment.These immunosuppressive lymphocytes include regulatory T cells(Tregs)and myeloid-derived suppressor cells(MDSCs).We used a low dose of doxorubicin(DOX)to induce ICD in combination with immune regulator 1-methylDL-tryptophan(1 MT)to suppress indoleamine 2,3-dioxygenase and overcome Treg-and MDSCassociated immune suppression.By co-encapsulation of DOX and 1 MT into a reduction-responsive polypeptide nanogel,the drugs were simultaneously released in the tumor cells and synergistically performed antitumor efficacy.After treatment,recruitment of Tregs and MDSCs was inhibited,and the frequency of tumor-infiltrating CD8+T cells was remarkably enhanced.These results demonstrated that the chemoimmunotherapy strategy effectively suppressed tumor growth without causing evident adverse effects,indicating its great potential in clinical cancer therapy.展开更多
基金supported by the Ministry of Science and Technology of China (2018ZX09711003-012)the National Natural Science Foundation of China (51873206, 51673189, 51829302, 51503202, 51833010 and 51520105004)the Program of Scientific Development of Jilin Province (20190103033JH)
文摘The key to improve the therapeutic efficacy for cancer treatment is to increase the delivery of drugs to tumors.For this purpose, tumor-microenvironment stimuliresponsive materials have great potential. Here, we prepared a new nanomedicine by bonding the conjugate of honokiol(HNK) and 5,6-dimethylxanthenone-4-acetic acid(DMXAA)to a glutathione(GSH)-responsive nanocarrier, poly(α-lipoic acid) polyethylene glycol. The nanomedicine would disintegrate due to the high level of GSH at the tumor sites,achieving the co-delivery of HNK and DMXAA, and realizing the combination therapy through close-range killing by HNK and long-range striking by DMXAA together. In a murine 4T1 breast tumor model, this strategy exhibited high tumor inhibition rate of 93%, and provided a valuable therapeutic choice for cancer therapy.
基金the National Natural Science Foundation(21776238,21476190,and 31801198)Hebei province Natural fund key projects(B2019203479)。
文摘Hypoxia is a hallmark of solid tumors,and it significantly impairs the overall anticancer efficacy,particularly photodynamic therapy(PDT).Herein,a catalase-like nanovesicle with near-infrared light-responsiveness,that is,platinum/gold nanoshell encapsulated chlorin e6(Ce6)/resveratrol(Res)liposome(Pt@Au-Ce6/Res-Lip),was developed to surmount this intractable issue.The Pt@Au-Ce6/Res-Lip can decompose overexpressed H_(2)O_(2)in tumor microenvironment to produce vast amounts of O_(2)for further enhancement of the PDT.Under the 808 nm laser irradiation,the Au nanoshells induced hyperthermia at the lesion site to ablate tumor cells,simultaneously inducing the controlled release of photosensitizer Ce6 and chemotherapeutic agent Res.Moreover,stimulated by 660 nm laser,numerous reactive oxygen species were formed to induce apoptosis and necrosis of tumor cells.With the cascade of trimodal therapeutic modality options(chemotherapy,photothermal therapy,and PDT),the Pt@Au-Ce6/Res-Lip showed ultrahigh tumor inhabitation rate in in vitro and in vivo studies,signifying that the Pt@AuCe6/Res-Lip nanovesicle is a promising candidate for effective cancer therapy.
基金supported by the National Natural Science Foundation of China(51973216,51873207,51803006,51833010,51673190,and 51603204)the Science and Technology Development Program of Jilin Province(20200404182YY)+1 种基金the Youth Talents Promotion Project of Jilin Province(181909)the Youth Innovation Promotion Association of Chinese Academy of Sciences(2019005)。
文摘Many conventional chemotherapeutics play an immune-modulating effect by inducing immunogenic cell death(ICD)in tumor cells.However,they hardly arouse strong antitumor immune response because the immunosuppressive lymphocytes are present in the tumor microenvironment.These immunosuppressive lymphocytes include regulatory T cells(Tregs)and myeloid-derived suppressor cells(MDSCs).We used a low dose of doxorubicin(DOX)to induce ICD in combination with immune regulator 1-methylDL-tryptophan(1 MT)to suppress indoleamine 2,3-dioxygenase and overcome Treg-and MDSCassociated immune suppression.By co-encapsulation of DOX and 1 MT into a reduction-responsive polypeptide nanogel,the drugs were simultaneously released in the tumor cells and synergistically performed antitumor efficacy.After treatment,recruitment of Tregs and MDSCs was inhibited,and the frequency of tumor-infiltrating CD8+T cells was remarkably enhanced.These results demonstrated that the chemoimmunotherapy strategy effectively suppressed tumor growth without causing evident adverse effects,indicating its great potential in clinical cancer therapy.
