Albumin nanoparticles are considered to be an effective way to load water-insoluble anticancer drugs and target tumors via the gp60-mediated pathway. Herein, we fabricated an albumin nanoparticle formulation for co-lo...Albumin nanoparticles are considered to be an effective way to load water-insoluble anticancer drugs and target tumors via the gp60-mediated pathway. Herein, we fabricated an albumin nanoparticle formulation for co-loading paclitaxel(PTX) and curcumin(CCM), both of which have prominent anticancer efficacy, via nanoparticle albumin-bound(NabTM) technology using high-pressure homogenization. The PTX/CCM co-bound albumin nanoparticles(PTX/CCM Alb-NPs) had a slightly greater particle size of ~250 nm than that of plain PTX AlbNPs and CCM Alb-NPs(~234 and ~134 nm, respectively), with spherical surface morphology and stable size maintenance. However, the zeta potential of PTX/CCM Alb-NPs(ca.-30 mV)was not significantly different from that of PTX or CCM Alb-NPs. The loaded PTX and CCM were released gradually from the PTX/CCM Alb-NPs over ~24 h(97.7 ± 1.7% and 76.2 ± 0.5%,respectively). Furthermore, PTX/CCM Alb-NPs appeared to be efficiently internalized into Mia Paca-2 cells and exhibited a 71% increased IC50 versus PTX Alb-NPs in terms of cytotoxicity to Mia Paca-2 cells. These results suggest that PTX/CCM Alb-NPs are a new potential anticancer agent for combination therapy.展开更多
Inspired by erythrocytes that contain oxygen-carrying hemoglobin(Hb)and that exhibit photo-driven activity,we introduce homogenous-sized erythrocyte-like Hb microgel(μGel)systems(5-6μm)that can(i)emit heat,(ii)suppl...Inspired by erythrocytes that contain oxygen-carrying hemoglobin(Hb)and that exhibit photo-driven activity,we introduce homogenous-sized erythrocyte-like Hb microgel(μGel)systems(5-6μm)that can(i)emit heat,(ii)supply oxygen,and(iii)generate reactive oxygen species(ROS;1O2)in response to near-infrared(NIR)laser irradiation.Hb μGels consist of Hb,bovine serum albumin(BSA),chlorin e6(Ce6)and erbium@lutetium upconverting nanoparticles(UCNPs;~35 nm)that effectively convert 808 nm NIR light to 660 nm visible light.These Hb μGels are capable of releasing oxygen to help generate sufficient reactive oxygen species(^(1)O_(2))from UCNPs/Ce6 under severely hypoxic condition upon NIR stimulation for efficient photodynamic activity.Moreover,the Hb μGels emit heat and increase surface temperature due to NIR light absorption by heme(iron protoporphyrin IX)and display photothermal activity.By changing the Hb/UCNP/Ce6 ratio and controlling the amount of NIR laser irradiation,it is possible to formulate bespoke Hb μGels with either photothermal or photodynamic activity or both in the context of combined therapeutic effect.These Hb μGels effectively suppress highly hypoxic 4T1 cell spheroid growth and xenograft mice tumors in vivo.展开更多
Objective: To evaluate the potential pharmacokinetic interactions of the anticancer agent gefitinib(Iressa?) and the oriental medications Guipi Decoction(归脾汤, GPD, Guibi-tang in Korean) and Bawu Decoction(八物汤, B...Objective: To evaluate the potential pharmacokinetic interactions of the anticancer agent gefitinib(Iressa?) and the oriental medications Guipi Decoction(归脾汤, GPD, Guibi-tang in Korean) and Bawu Decoction(八物汤, BWD, Palmul-tang in Korean). Methods: Methylcellulose(MC, control), GPD(1,200 mg/kg), or BWD(6,000 mg/kg) was orally administered to rats either as a single dose or multiple doses prior to gefitinib administration. To examine the effects of a single dose of the herbal medicines, gefitinib(10 mg/kg) was orally administered after 5 min or 1 h of MC or the herbal medicine pretreatments. To examine the effects of the multiple doses of the herbal medicines, gefitinib(10 mg/kg) was orally administered following 7 consecutive days of the administration of MC or each herbal medicine. The plasma concentrations of gefitinib were determined with liquid chromatography-tandem mass spectrometry assay. The plasma concentration-time profiles of gefitinib were analyzed with a noncompartmental analysis. Results: Gefitinib was rapidly absorbed and showed a monoexponential decline with an elimination half-life of 3.7–4.1 h. The pharmacokinetics of gefitinib was not affected by GPD pretreatment. However, a significantly lower maximum plasma concentration(Cmax, P<0.05) and area under the curve(P<0.05), and a delayed time to reach Cmax(Tmax, P<0.01) were observed in both single-and multipledose BWD-pretreated rats compared with the control rats. Conclusions: BWD and not GPD might delay and interfere with gefitinib absorption. Further evaluations of the clinical significance of these findings are needed.展开更多
文摘Albumin nanoparticles are considered to be an effective way to load water-insoluble anticancer drugs and target tumors via the gp60-mediated pathway. Herein, we fabricated an albumin nanoparticle formulation for co-loading paclitaxel(PTX) and curcumin(CCM), both of which have prominent anticancer efficacy, via nanoparticle albumin-bound(NabTM) technology using high-pressure homogenization. The PTX/CCM co-bound albumin nanoparticles(PTX/CCM Alb-NPs) had a slightly greater particle size of ~250 nm than that of plain PTX AlbNPs and CCM Alb-NPs(~234 and ~134 nm, respectively), with spherical surface morphology and stable size maintenance. However, the zeta potential of PTX/CCM Alb-NPs(ca.-30 mV)was not significantly different from that of PTX or CCM Alb-NPs. The loaded PTX and CCM were released gradually from the PTX/CCM Alb-NPs over ~24 h(97.7 ± 1.7% and 76.2 ± 0.5%,respectively). Furthermore, PTX/CCM Alb-NPs appeared to be efficiently internalized into Mia Paca-2 cells and exhibited a 71% increased IC50 versus PTX Alb-NPs in terms of cytotoxicity to Mia Paca-2 cells. These results suggest that PTX/CCM Alb-NPs are a new potential anticancer agent for combination therapy.
基金This work was supported by a National Research Foundation of Korea(NRF)grants funded by the Korean government(No.NRF-2019R1A5A2027340)the Bio&Medical Technology Development Program of the National Research Foundation(NRF)funded by the Korean government(MSIT)(No.NRF-2022M3A9G8017220).
文摘Inspired by erythrocytes that contain oxygen-carrying hemoglobin(Hb)and that exhibit photo-driven activity,we introduce homogenous-sized erythrocyte-like Hb microgel(μGel)systems(5-6μm)that can(i)emit heat,(ii)supply oxygen,and(iii)generate reactive oxygen species(ROS;1O2)in response to near-infrared(NIR)laser irradiation.Hb μGels consist of Hb,bovine serum albumin(BSA),chlorin e6(Ce6)and erbium@lutetium upconverting nanoparticles(UCNPs;~35 nm)that effectively convert 808 nm NIR light to 660 nm visible light.These Hb μGels are capable of releasing oxygen to help generate sufficient reactive oxygen species(^(1)O_(2))from UCNPs/Ce6 under severely hypoxic condition upon NIR stimulation for efficient photodynamic activity.Moreover,the Hb μGels emit heat and increase surface temperature due to NIR light absorption by heme(iron protoporphyrin IX)and display photothermal activity.By changing the Hb/UCNP/Ce6 ratio and controlling the amount of NIR laser irradiation,it is possible to formulate bespoke Hb μGels with either photothermal or photodynamic activity or both in the context of combined therapeutic effect.These Hb μGels effectively suppress highly hypoxic 4T1 cell spheroid growth and xenograft mice tumors in vivo.
基金Supported by the Comprehensive and Interactive Medicine InstituteNational Research Foundation of Korea(No.2012R1A2A2A02044997)
文摘Objective: To evaluate the potential pharmacokinetic interactions of the anticancer agent gefitinib(Iressa?) and the oriental medications Guipi Decoction(归脾汤, GPD, Guibi-tang in Korean) and Bawu Decoction(八物汤, BWD, Palmul-tang in Korean). Methods: Methylcellulose(MC, control), GPD(1,200 mg/kg), or BWD(6,000 mg/kg) was orally administered to rats either as a single dose or multiple doses prior to gefitinib administration. To examine the effects of a single dose of the herbal medicines, gefitinib(10 mg/kg) was orally administered after 5 min or 1 h of MC or the herbal medicine pretreatments. To examine the effects of the multiple doses of the herbal medicines, gefitinib(10 mg/kg) was orally administered following 7 consecutive days of the administration of MC or each herbal medicine. The plasma concentrations of gefitinib were determined with liquid chromatography-tandem mass spectrometry assay. The plasma concentration-time profiles of gefitinib were analyzed with a noncompartmental analysis. Results: Gefitinib was rapidly absorbed and showed a monoexponential decline with an elimination half-life of 3.7–4.1 h. The pharmacokinetics of gefitinib was not affected by GPD pretreatment. However, a significantly lower maximum plasma concentration(Cmax, P<0.05) and area under the curve(P<0.05), and a delayed time to reach Cmax(Tmax, P<0.01) were observed in both single-and multipledose BWD-pretreated rats compared with the control rats. Conclusions: BWD and not GPD might delay and interfere with gefitinib absorption. Further evaluations of the clinical significance of these findings are needed.