Targetingmitochondria via nano platform emerged as an attractive anti-tumor pathway due to the central regulation role in cellar apoptosis and drug resistance.Here,a mitochondria-targeting nanoparticle(TOS-PDA-PEG-TPP...Targetingmitochondria via nano platform emerged as an attractive anti-tumor pathway due to the central regulation role in cellar apoptosis and drug resistance.Here,a mitochondria-targeting nanoparticle(TOS-PDA-PEG-TPP)was designed to precisely deliver polydopamine(PDA)as the photothermal agent and alphatocopherol succinate(α-TOS)as the chemotherapeutic drug to the mitochondria of the tumor cells,which inhibits the tumor growth through chemo-and photothermal-synergistic therapies.TOSPDA-PEG-TPP was constructed by coating PDA on the surface of TOS NPs self-assembled byα-TOS,followed by grafting PEGand triphenylphosphonium(TPP)on their surface to prolong the blood circulation time and target delivery of TOS and PDA to the mitochondria of tumor cells.In vitro studies showed that TOS-PDA-PEGTPP could be efficiently internalized by tumor cells and accumulated atmitochondria,resulting in cellular apoptosis and synergistic inhibition of tumor cell proliferation.In vivo studies demonstrated that TOS-PDA-PEG-TPP could be efficiently localized at tumor sites and significantly restrain the tumor growth under NIR irradiation without apparent toxicity or deleterious effects.Conclusively,the combination strategy adopted for functional nanodrugs construction aimed at target-delivering therapeutic agents with different action mechanisms to the same intracellular organelles can be extended to other nanodrugs-dependent therapeutic systems.展开更多
Late-stage modification of peptides and proteins meets the increasing demand in biochemical and pharmaceutical communities. These modification strategies could provide functionalized nonproteinogenic analogues with en...Late-stage modification of peptides and proteins meets the increasing demand in biochemical and pharmaceutical communities. These modification strategies could provide functionalized nonproteinogenic analogues with enhanced biological activities or improved therapeutic capabilities compared to their natural counterparts. Recent years, transition-metal-promoted functionalization of ubiquitous C-H bonds has been emerged as a powerful and tunable tool in this area, both for backbone diversifications and labeling of specific moieties. These reactions were flexible and expedient in both academic and industrial laboratories, especially considering their atom and step-economy, good functional group compatibility, accurate site selectivity. This review surveys the progress achieved in the late-stage modification of peptides and proteins utilizing transition-metal-catalyzed C-H functionalization with C-C and C-X(F, Cl, O, N, B, etc.) bonds formation.展开更多
基金supported by the Medico-Engineering Cooperation Funds from the University of Electronic Science and Technology of China(ZYGX2021YGCX018)Sichuan Provincial Science Fund for applied basic research of China(2020YJ0108)Sichuan Provincial Science Fund for applied basic research of China(2020YFS0424).
文摘Targetingmitochondria via nano platform emerged as an attractive anti-tumor pathway due to the central regulation role in cellar apoptosis and drug resistance.Here,a mitochondria-targeting nanoparticle(TOS-PDA-PEG-TPP)was designed to precisely deliver polydopamine(PDA)as the photothermal agent and alphatocopherol succinate(α-TOS)as the chemotherapeutic drug to the mitochondria of the tumor cells,which inhibits the tumor growth through chemo-and photothermal-synergistic therapies.TOSPDA-PEG-TPP was constructed by coating PDA on the surface of TOS NPs self-assembled byα-TOS,followed by grafting PEGand triphenylphosphonium(TPP)on their surface to prolong the blood circulation time and target delivery of TOS and PDA to the mitochondria of tumor cells.In vitro studies showed that TOS-PDA-PEGTPP could be efficiently internalized by tumor cells and accumulated atmitochondria,resulting in cellular apoptosis and synergistic inhibition of tumor cell proliferation.In vivo studies demonstrated that TOS-PDA-PEG-TPP could be efficiently localized at tumor sites and significantly restrain the tumor growth under NIR irradiation without apparent toxicity or deleterious effects.Conclusively,the combination strategy adopted for functional nanodrugs construction aimed at target-delivering therapeutic agents with different action mechanisms to the same intracellular organelles can be extended to other nanodrugs-dependent therapeutic systems.
基金the support from the National Key R&D Program of China(No. 2017YFA0505400)the National Natural Science Foundation of China (Nos. 21572214, 21702200)
文摘Late-stage modification of peptides and proteins meets the increasing demand in biochemical and pharmaceutical communities. These modification strategies could provide functionalized nonproteinogenic analogues with enhanced biological activities or improved therapeutic capabilities compared to their natural counterparts. Recent years, transition-metal-promoted functionalization of ubiquitous C-H bonds has been emerged as a powerful and tunable tool in this area, both for backbone diversifications and labeling of specific moieties. These reactions were flexible and expedient in both academic and industrial laboratories, especially considering their atom and step-economy, good functional group compatibility, accurate site selectivity. This review surveys the progress achieved in the late-stage modification of peptides and proteins utilizing transition-metal-catalyzed C-H functionalization with C-C and C-X(F, Cl, O, N, B, etc.) bonds formation.
