This study primarily focused on the systematic assessment of both in vitro and in vivo anti-tumor effects of docetaxel-loaded polyethylene glycol（PEG）2000-polycaprolactone（PCL）2600 micelles on hormone-refractory p...This study primarily focused on the systematic assessment of both in vitro and in vivo anti-tumor effects of docetaxel-loaded polyethylene glycol（PEG）2000-polycaprolactone（PCL）2600 micelles on hormone-refractory prostate cancer（HRPC）. By using solvent evaporation method, PEG-PCL was chosen to prepare doxetaxel（DTX）-loaded mPEG-PCL micelles（DTX-PMs）, with the purpose of eliminating side effects of the commercial formulation（Tween 80） and prolonging the blood circulation time. The prepared DTX-PMs had an average particle size of 25.19±2.36 nm, a zeta potential of 0.64±0.15 mV, a polydispersity index of 0.56±0.03, a drug loading of（8.72±1.05）%, and an encapsulation efficiency of（98.1±8.4）%. In vitro cytotoxicity studies indicated that DTX-PMs could effectively kill LNCap-C4-2B cells and show a dose- and time-dependent efficacy. The hemolysis test showed that DTX-PMs had less hemocytolysis than the commercial product of Duopafei. A sustained in vitro release behavior and prolonged circulation time in blood vessels were observed in the DTX-PMs. Furthermore, when compared with Duopafei, the DTX-PMs dramatically reduced the prostate specific antigen（PSA） level and tumor growth of prostate tumor-bearing nude mice in vivo. In conclusion, the DTX-PMs can lower systemic side effects, improve anti-tumor activity with prolonged blood circulation time, and will bring an alternative to patients with HRPC.展开更多
Multifunctional nanoparticles combining diagnostic and therapeutic agents into a single platform make cancer theranostics possible and have attracted wide interests in the field. In this study, a multifunctional nanoc...Multifunctional nanoparticles combining diagnostic and therapeutic agents into a single platform make cancer theranostics possible and have attracted wide interests in the field. In this study, a multifunctional nanocomposite based on dextran and superparamagnetic iron oxide nanoparticles （SPIO） was prepared for drug delivery and magnetic resonance imaging （MRI）. Amphiphilic dextran was synthesized by grafting stearyl acid onto the carbohydrate backbone, and micelle was formed by the resulted amphiphilic dextran with low critical micelle concentration at 1.8 mg L^-1. Doxorubicin （DOX） and a cluster of the manganese-doped iron oxide nanoparticles （Mn-SPIO） nanocrystals were then coencapsulated successfully inside the core of dextran micelles, resulting in nanocomposites with diameter at about 100 nm. Cell culture experiments demonstrated the potential of these Mn-SPIO/DOX nanocomposites as an effective multifunctional nanoplat- lk）rm for the delivery of anticancer drug DOX with a loading content （DLC） of 16 %. Confocal laser scanning microscopy reveals that the Mn-SPIO/DOX had excellent internalization ability against MCF-7/Adr cells after 2-h labeling compared with flee DOX.HCI. Under a 3.0-T MRI scanner, Mn-SPIO/ DOX nanocomposite-labeled cells in gelatin phantom show much darker images than the control. Their transverse relaxation （T2） rate is also significantly higher than that of the control cells （33.9 versus 2.3 s^-1）. Our result offers an effective strategy to treat MCF-7/Adr at optimized low dosages with imaging capability.展开更多
Poly(2-oxazoline)(POx)is a kind of polymeric amides that can be viewed as conformational isomers of polypeptides with excellent cyto-and hemo-compatibility,and is promising to be used as drug carriers.However,the drug...Poly(2-oxazoline)(POx)is a kind of polymeric amides that can be viewed as conformational isomers of polypeptides with excellent cyto-and hemo-compatibility,and is promising to be used as drug carriers.However,the drug loading capacity(DLC)of POx for many drugs is still low except several hydrophobic ones including paclitaxel(PTX).Herein,we prepared a series of amphiphilic POx block copolymers with various functional groups,and investigated the relationship between functional structures and the DLC.Functional POxs with benzyl,carboxyl,and amino groups in the side-chain were synthesized based on a poly(2-methyl-2-oxazoline)-block-poly(2-buty1-2-oxazoline-co-2-buteny1-2-oxazoline)(PMeOx-P(nBuOx-co-ButenOx),PMBEOx)precursor,followed by click reaction between vinyl and the 2-phenylethanethiol,thioglycolic acid and cysteamine.Using thin-film hydration method,eight commonly used drugs with various characteristics were encapsulated within these functional POx polymers.We found that amine-containing drugs were more easily encapsulated by POx with carboxyl groups,while amine functionalities in POx enhanced the loading capacity of drugs with carboxyl groups.In addition,n-n interactions resulted in enhanced DLC of most drugs,except several hydrophobic drugs with aromatic to total carbon ratios less than 0.5.In general,we could successfully encapsulate all the selected drugs with a DLC%over 10%using properly selected functional POxs.The above results confirm that the DLC of polymeric carriers can be adjusted by modifying the functional groups,and the prepared series of functional POxs provide an option for various drug loadings.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.81373342)the Nature Science Foundation of Beijing(No.2141004)
文摘This study primarily focused on the systematic assessment of both in vitro and in vivo anti-tumor effects of docetaxel-loaded polyethylene glycol（PEG）2000-polycaprolactone（PCL）2600 micelles on hormone-refractory prostate cancer（HRPC）. By using solvent evaporation method, PEG-PCL was chosen to prepare doxetaxel（DTX）-loaded mPEG-PCL micelles（DTX-PMs）, with the purpose of eliminating side effects of the commercial formulation（Tween 80） and prolonging the blood circulation time. The prepared DTX-PMs had an average particle size of 25.19±2.36 nm, a zeta potential of 0.64±0.15 mV, a polydispersity index of 0.56±0.03, a drug loading of（8.72±1.05）%, and an encapsulation efficiency of（98.1±8.4）%. In vitro cytotoxicity studies indicated that DTX-PMs could effectively kill LNCap-C4-2B cells and show a dose- and time-dependent efficacy. The hemolysis test showed that DTX-PMs had less hemocytolysis than the commercial product of Duopafei. A sustained in vitro release behavior and prolonged circulation time in blood vessels were observed in the DTX-PMs. Furthermore, when compared with Duopafei, the DTX-PMs dramatically reduced the prostate specific antigen（PSA） level and tumor growth of prostate tumor-bearing nude mice in vivo. In conclusion, the DTX-PMs can lower systemic side effects, improve anti-tumor activity with prolonged blood circulation time, and will bring an alternative to patients with HRPC.
基金The project was supported by the National Natural Science Foundation of China(20673021,20873024)Natural Science Foundation of Fujian Province,China(2010J01038)~~
基金supported by the National Basic Research Program of China(2013CB933903)the National Key Technology Research and Development Program(2012BAI23B08)+1 种基金the National Natural Science Foundation of China(51173117)the Scientific Research Start-up Fund of Kunming University of Science and Technology(KKSY201305089)
文摘Multifunctional nanoparticles combining diagnostic and therapeutic agents into a single platform make cancer theranostics possible and have attracted wide interests in the field. In this study, a multifunctional nanocomposite based on dextran and superparamagnetic iron oxide nanoparticles （SPIO） was prepared for drug delivery and magnetic resonance imaging （MRI）. Amphiphilic dextran was synthesized by grafting stearyl acid onto the carbohydrate backbone, and micelle was formed by the resulted amphiphilic dextran with low critical micelle concentration at 1.8 mg L^-1. Doxorubicin （DOX） and a cluster of the manganese-doped iron oxide nanoparticles （Mn-SPIO） nanocrystals were then coencapsulated successfully inside the core of dextran micelles, resulting in nanocomposites with diameter at about 100 nm. Cell culture experiments demonstrated the potential of these Mn-SPIO/DOX nanocomposites as an effective multifunctional nanoplat- lk）rm for the delivery of anticancer drug DOX with a loading content （DLC） of 16 %. Confocal laser scanning microscopy reveals that the Mn-SPIO/DOX had excellent internalization ability against MCF-7/Adr cells after 2-h labeling compared with flee DOX.HCI. Under a 3.0-T MRI scanner, Mn-SPIO/ DOX nanocomposite-labeled cells in gelatin phantom show much darker images than the control. Their transverse relaxation （T2） rate is also significantly higher than that of the control cells （33.9 versus 2.3 s^-1）. Our result offers an effective strategy to treat MCF-7/Adr at optimized low dosages with imaging capability.
基金the National Natural Science Foundation of China(Nos.51673185,51973215,51673189,51829302,52003268 and 52025035)as well as the support from the Youth Innovation Promotion Association of Chinese Academy of Sciences(No.2020232).
文摘Poly(2-oxazoline)(POx)is a kind of polymeric amides that can be viewed as conformational isomers of polypeptides with excellent cyto-and hemo-compatibility,and is promising to be used as drug carriers.However,the drug loading capacity(DLC)of POx for many drugs is still low except several hydrophobic ones including paclitaxel(PTX).Herein,we prepared a series of amphiphilic POx block copolymers with various functional groups,and investigated the relationship between functional structures and the DLC.Functional POxs with benzyl,carboxyl,and amino groups in the side-chain were synthesized based on a poly(2-methyl-2-oxazoline)-block-poly(2-buty1-2-oxazoline-co-2-buteny1-2-oxazoline)(PMeOx-P(nBuOx-co-ButenOx),PMBEOx)precursor,followed by click reaction between vinyl and the 2-phenylethanethiol,thioglycolic acid and cysteamine.Using thin-film hydration method,eight commonly used drugs with various characteristics were encapsulated within these functional POx polymers.We found that amine-containing drugs were more easily encapsulated by POx with carboxyl groups,while amine functionalities in POx enhanced the loading capacity of drugs with carboxyl groups.In addition,n-n interactions resulted in enhanced DLC of most drugs,except several hydrophobic drugs with aromatic to total carbon ratios less than 0.5.In general,we could successfully encapsulate all the selected drugs with a DLC%over 10%using properly selected functional POxs.The above results confirm that the DLC of polymeric carriers can be adjusted by modifying the functional groups,and the prepared series of functional POxs provide an option for various drug loadings.
