Black phosphorus(BP)nano-materials,especially BP quantum dots(BPQDs),performs outstanding photothermal antitumor effects,excellent biocompatibility and biodegradability.However,there are several challenges to overcome...Black phosphorus(BP)nano-materials,especially BP quantum dots(BPQDs),performs outstanding photothermal antitumor effects,excellent biocompatibility and biodegradability.However,there are several challenges to overcome before offering real benefits,such as poor stability,poor dispersibility as well as difficulty in tailoring other functions.Here,a“three-in-one”mitochondria-targeted BP nano-platform,called as BPQD-PEG-TPP,was designed.In this nano-platform,BPQDs were covalently grafted with a heterobifunctional PEG,in which one end was an aryl diazo group capable of reacting with BPQDs to form a covalent bond and the other end was a mitochondria-targeted triphenylphosphine(TPP)group.In addition to its excellent near-infrared photothermal properties,BPQD-PEG-TPP had much enhanced stability and dispersibility under physiological conditions,efficient mitochondria targeting and promoted ROS production through a photothermal effect.Both in vitro and in vivo experiments demonstrated that BPQD-PEG-TPP performed much superior photothermal cytotoxicity than BPQDs and BPQD-PEG as the mitochondria targeted PTT.Thus this“three-in-one”nanoplatform fabricated through polymer grafting,with excellent stability,dispersibility and negligible side effects,might be a promising strategy for mitochondria-targeted photothermal cancer therapy.展开更多
Abnormal protein expression or activities are associated with many diseases,especially cancer.Therefore,down-regulating the proteins involved in cancer cell survival proved to be an effective strategy for cancer treat...Abnormal protein expression or activities are associated with many diseases,especially cancer.Therefore,down-regulating the proteins involved in cancer cell survival proved to be an effective strategy for cancer treatment—a number of drugs based on proteolysis-targeting chimaera(PROTAC)mechanism have demonstrated clinical efficacy.Recent progress in the PROTAC strategy includes identification of the structure of the first ternary eutectic complex,extra-terminal domain-4-PROTAC-VonHippel-Lindau(BRD4-PROTAC-VHL),and PROTAC ARV-110 has entered clinical trials for the treatment of prostate cancer in 2019.These discoveries strongly proved the value of the PROTAC strategy.In this review,we summarize recent meaningful research of PROTACs,including the molecular design and optimization strategy as well as clinical application of candidate molecules.We hope to provide useful insights for rational design of PROTACs.展开更多
基金We are grateful for the financial support from National Natural Science Foundation of China(51703258,81772449 and 81971081)Guangzhou science technology and innovation commission(201804010309 and 201803010090)Science,Technology&Innovation Commission of Shenzhen Municipality(JCYJ20180307154606793 and JCYJ20180507181654186).
文摘Black phosphorus(BP)nano-materials,especially BP quantum dots(BPQDs),performs outstanding photothermal antitumor effects,excellent biocompatibility and biodegradability.However,there are several challenges to overcome before offering real benefits,such as poor stability,poor dispersibility as well as difficulty in tailoring other functions.Here,a“three-in-one”mitochondria-targeted BP nano-platform,called as BPQD-PEG-TPP,was designed.In this nano-platform,BPQDs were covalently grafted with a heterobifunctional PEG,in which one end was an aryl diazo group capable of reacting with BPQDs to form a covalent bond and the other end was a mitochondria-targeted triphenylphosphine(TPP)group.In addition to its excellent near-infrared photothermal properties,BPQD-PEG-TPP had much enhanced stability and dispersibility under physiological conditions,efficient mitochondria targeting and promoted ROS production through a photothermal effect.Both in vitro and in vivo experiments demonstrated that BPQD-PEG-TPP performed much superior photothermal cytotoxicity than BPQDs and BPQD-PEG as the mitochondria targeted PTT.Thus this“three-in-one”nanoplatform fabricated through polymer grafting,with excellent stability,dispersibility and negligible side effects,might be a promising strategy for mitochondria-targeted photothermal cancer therapy.
基金the support from grants(Nos.81573281)of National Natural Science Foundation of Chinasupport from Double First-Class initiative Innovation team project of China Pharmaceutical University(Nos.CPU2018GF11 and CPU2018GY34,China).
文摘Abnormal protein expression or activities are associated with many diseases,especially cancer.Therefore,down-regulating the proteins involved in cancer cell survival proved to be an effective strategy for cancer treatment—a number of drugs based on proteolysis-targeting chimaera(PROTAC)mechanism have demonstrated clinical efficacy.Recent progress in the PROTAC strategy includes identification of the structure of the first ternary eutectic complex,extra-terminal domain-4-PROTAC-VonHippel-Lindau(BRD4-PROTAC-VHL),and PROTAC ARV-110 has entered clinical trials for the treatment of prostate cancer in 2019.These discoveries strongly proved the value of the PROTAC strategy.In this review,we summarize recent meaningful research of PROTACs,including the molecular design and optimization strategy as well as clinical application of candidate molecules.We hope to provide useful insights for rational design of PROTACs.
