Glioma is one of the most common malignant tumors of the central nervous system,leading high mortality rates in human.Aggregation-induced emission(AIE)photosensitizers-based photodynamic therapy(PDT)has emerged as a p...Glioma is one of the most common malignant tumors of the central nervous system,leading high mortality rates in human.Aggregation-induced emission(AIE)photosensitizers-based photodynamic therapy(PDT)has emerged as a promising therapeutic strategy for least-invasive treatment of glioma,which involves local irradiation of the tumor using an external near-infrared(NIR)laser.Unfortunately,most AIE photosensitizers suffered from poorly penetration of the visible light excitation,bad spatiotemporal resolution in deep tissues and low efficient blood-brain barrier(BBB)crossing ability,which greatly limited the clinical practice of AIE photosensitizers for especially deep-seated brain tumor treatment.In this work,we developed a multifunctional NIR-driven theranostic agent through hybrid of AIE photosensitizers TIND with rare-earth doping nanoparticles(RENPs)NaGdF4:Nd/Yb/Tm with up/down dual-mode conversion luminescence.The theranostic agent was further decorated with D-type neuropeptide DNPY for crossing BBB and targeting glioma.Under the 808-nm light irradiation,the down-conversion NIR-II luminescence could indicate the position glioma and the upconversion NIR-I luminescence could trigger the AIE photosensitizers producing reactive oxygen species to inhibit orthotopic glioma tumor growth in situ.These results demonstrate that the integration of Dtype neuropeptide,AIE photosensitizers and RENPs could be promising candidates for in vivo NIR-II fluorescence image-guided through-skull PDT treatments of brain tumors.展开更多
With the evolution of nanomedicine,the past decades witnessed diversified nanomaterials as marvelous antitumor tools ushering in a new era of tumor diagnosis and treatment.Among them,two-dimensional layered nano-mater...With the evolution of nanomedicine,the past decades witnessed diversified nanomaterials as marvelous antitumor tools ushering in a new era of tumor diagnosis and treatment.Among them,two-dimensional layered nano-material as an emerging class of nanomaterials has one dimension less than 100 nm,showing a high specific area and the thinnest sheet-like structure(Liu S,Pan X,Liu H.Twodimensional nanomaterials for photothermal therapy.Angew Chem Int Ed 2020;59:5890–900).The discovery of graphene drove the exploration of various new two-dimensional layered nanomaterials for tumor diagnosis and treatment including graphene-based nanomaterials,black phosphorus(BP),transition metal dichalcogenides(TMDs),layered double hydroxides(LDHs),and bismuth oxyhalides(BiOX,X=F,Cl,Br,I)(Ma H,Xue MQ.Recent advances in the photothermal applications of two-dimensional nanomaterial:photothermal therapy and beyond.J Mater Chem 2021;9:17569).On the one hand,they exhibit strong near-infrared(NIR)absorption and the capacity of optimizing corresponding properties by adjusting the crystal structure.On the other hand,they own unique strengths such as fantastic physicochemical properties(graphene-based nanomaterials),high loading capacity(BP),distinct phase-dependent optical properties(TMDs),a specific chemical response to the tumor microenvironment(LDHs),and large X-ray attenuation coefficient(BiOX).Herein,we briefly introduce three typical two-dimensional layered nanomaterials,their prospects and future research priorities in tumor diagnosis and treatment are concluded.展开更多
Peptide-drug conjugates have achieved considerable development and application as a novel strategy for targeted delivery of anticancer drugs. Bioactive peptides induced calcium deposition can irreversibly assist inhib...Peptide-drug conjugates have achieved considerable development and application as a novel strategy for targeted delivery of anticancer drugs. Bioactive peptides induced calcium deposition can irreversibly assist inhibition of tumors. However, active regulation of calcium level through signal transduction of bioactive substances has not been reported yet. In this study, novel neuropeptide-doxorubicin conjugates(NP-DOX) with lysosome-specific acid response were described for neuropeptide Y_1 receptor(Y_1R)-overexpressed triple-negative breast cancer. The delivery mechanism of NP-DOX was clarified that diverse pathways were involved, including intracellular and intercellular transport. Importantly, up-regulation of Y_1 R-mediated intracellular calcium level via second messenger inositol triphosphate was presented in NP-DOX treated MDA-MB-231 cells. In vivo antitumor efficacy demonstrated that NP-DOX showed less organ toxicity and enhanced tumor inhibition benefited from its controlled release and Y_1R-mediated calcium deposition, compared with free DOX. This bioconjugate is a proof-of-concept confirming that neuropeptide-mediated control of signaling responses in neuropeptide-drug conjugates enables great potential for further applications in tumor chemotherapy.展开更多
基金Natural Science Foundation of China,Grant/Award Numbers:T2222021,32011530115,32025021National Key R&D Programs,Grant/Award Number:2019YFE0198700+2 种基金Science and Technology Bureau of Ningbo City,Grant/Award Numbers:2020Z094,2021Z072Excellent Member of Youth Innovation Promotion Association Foundation of CAS,Grant/Award Number:Y2021079Innovation and Technology Commission,Grant/Award Number:MHP/047/19。
文摘Glioma is one of the most common malignant tumors of the central nervous system,leading high mortality rates in human.Aggregation-induced emission(AIE)photosensitizers-based photodynamic therapy(PDT)has emerged as a promising therapeutic strategy for least-invasive treatment of glioma,which involves local irradiation of the tumor using an external near-infrared(NIR)laser.Unfortunately,most AIE photosensitizers suffered from poorly penetration of the visible light excitation,bad spatiotemporal resolution in deep tissues and low efficient blood-brain barrier(BBB)crossing ability,which greatly limited the clinical practice of AIE photosensitizers for especially deep-seated brain tumor treatment.In this work,we developed a multifunctional NIR-driven theranostic agent through hybrid of AIE photosensitizers TIND with rare-earth doping nanoparticles(RENPs)NaGdF4:Nd/Yb/Tm with up/down dual-mode conversion luminescence.The theranostic agent was further decorated with D-type neuropeptide DNPY for crossing BBB and targeting glioma.Under the 808-nm light irradiation,the down-conversion NIR-II luminescence could indicate the position glioma and the upconversion NIR-I luminescence could trigger the AIE photosensitizers producing reactive oxygen species to inhibit orthotopic glioma tumor growth in situ.These results demonstrate that the integration of Dtype neuropeptide,AIE photosensitizers and RENPs could be promising candidates for in vivo NIR-II fluorescence image-guided through-skull PDT treatments of brain tumors.
基金the National Natural Science Foundation of China(32025021,31971292,and 32111540257)National Key R&D Program of China(2018YFC0910601,2019YFA0405603)+1 种基金the Science&Technology Bureau of Ningbo City(2020Z094)the Key R&D Program of Zhejiang Province(2020C03110)。
文摘With the evolution of nanomedicine,the past decades witnessed diversified nanomaterials as marvelous antitumor tools ushering in a new era of tumor diagnosis and treatment.Among them,two-dimensional layered nano-material as an emerging class of nanomaterials has one dimension less than 100 nm,showing a high specific area and the thinnest sheet-like structure(Liu S,Pan X,Liu H.Twodimensional nanomaterials for photothermal therapy.Angew Chem Int Ed 2020;59:5890–900).The discovery of graphene drove the exploration of various new two-dimensional layered nanomaterials for tumor diagnosis and treatment including graphene-based nanomaterials,black phosphorus(BP),transition metal dichalcogenides(TMDs),layered double hydroxides(LDHs),and bismuth oxyhalides(BiOX,X=F,Cl,Br,I)(Ma H,Xue MQ.Recent advances in the photothermal applications of two-dimensional nanomaterial:photothermal therapy and beyond.J Mater Chem 2021;9:17569).On the one hand,they exhibit strong near-infrared(NIR)absorption and the capacity of optimizing corresponding properties by adjusting the crystal structure.On the other hand,they own unique strengths such as fantastic physicochemical properties(graphene-based nanomaterials),high loading capacity(BP),distinct phase-dependent optical properties(TMDs),a specific chemical response to the tumor microenvironment(LDHs),and large X-ray attenuation coefficient(BiOX).Herein,we briefly introduce three typical two-dimensional layered nanomaterials,their prospects and future research priorities in tumor diagnosis and treatment are concluded.
基金financially supported by the Key R&D Program of Zhejiang Province (No.2020C03110)the National Natural Science Foundation of China (Nos.T2222021, 32011530115,32025021)+1 种基金the Science&Technology Bureau of Ningbo City (Nos.2020Z094, 2021Z072)Excellent Member of Youth Innovation Promotion Association Foundation of CAS (No.Y2021079)。
文摘Peptide-drug conjugates have achieved considerable development and application as a novel strategy for targeted delivery of anticancer drugs. Bioactive peptides induced calcium deposition can irreversibly assist inhibition of tumors. However, active regulation of calcium level through signal transduction of bioactive substances has not been reported yet. In this study, novel neuropeptide-doxorubicin conjugates(NP-DOX) with lysosome-specific acid response were described for neuropeptide Y_1 receptor(Y_1R)-overexpressed triple-negative breast cancer. The delivery mechanism of NP-DOX was clarified that diverse pathways were involved, including intracellular and intercellular transport. Importantly, up-regulation of Y_1 R-mediated intracellular calcium level via second messenger inositol triphosphate was presented in NP-DOX treated MDA-MB-231 cells. In vivo antitumor efficacy demonstrated that NP-DOX showed less organ toxicity and enhanced tumor inhibition benefited from its controlled release and Y_1R-mediated calcium deposition, compared with free DOX. This bioconjugate is a proof-of-concept confirming that neuropeptide-mediated control of signaling responses in neuropeptide-drug conjugates enables great potential for further applications in tumor chemotherapy.
基金financially supported by the National Nature Science Foundation of China (32025021, 52303215, 32011530115, 32111540257, and 32311530040)the Key R&D Program of Zhejiang Province (2020C03110)the Science & Technology Bureau of Ningbo City (2020Z094, 2021Z072, 2021J029, and 2023J065)。