We measured the^(19)O+^(12)C fusion excitation function using the MATE active-target TPC at IMP for 9.7≤Ec.m.≤16.9 MeV.The results agree well with DC-TDHF and TDHF predictions,demonstrating the importance of dynamic...We measured the^(19)O+^(12)C fusion excitation function using the MATE active-target TPC at IMP for 9.7≤Ec.m.≤16.9 MeV.The results agree well with DC-TDHF and TDHF predictions,demonstrating the importance of dynamical effects near the barrier,but disagree with earlier MUSIC-based measurements.The^(19)O+^(12)C system exhibits a maximum fusion cross section consistent with those ofβ-stable O+C systems.A linear dependence of 1/E_(cr) and closest-approach distance on oxygen mass number is observed for^(17,18,19)O+^(12)C,indicating that additional valence neutrons lower the critical energy.V-shaped excitation structures appear for^(17)O and^(19)O,and the anomalous suppression previously reported for^(17)O calls for further experimental and theoretical study.展开更多
Hyaluronic acid(HA) is a natural ligand of tumor-targeted drug delivery systems(DDS) due to the relevant CD44 receptor overexpressed on tumor cell membranes. However, other HA receptors(HARE and LYVE-1) are also overe...Hyaluronic acid(HA) is a natural ligand of tumor-targeted drug delivery systems(DDS) due to the relevant CD44 receptor overexpressed on tumor cell membranes. However, other HA receptors(HARE and LYVE-1) are also overexpressing in the reticuloendothelial system(RES). Therefore,polyethylene glycol(PEG) modification of HA-based DDS is necessary to reduce RES capture.Unfortunately, pegylation remarkably inhibits tumor cellular uptake and endosomal escapement,significantly compromising the in vivo antitumor efficacy. Herein, we developed a Dox-loaded HA-based transformable supramolecular nanoplatform(Dox/HCVBP) to overcome this dilemma. Dox/HCVBP contains a tumor extracellular acidity-sensitive detachable PEG shell achieved by a benzoic imine linkage.The in vitro and in vivo investigations further demonstrated that Dox/HCVBP could be in a "stealth" state at blood stream for a long circulation time due to the buried HA ligands and the minimized nonspecific interaction by PEG shell. However, it could transform into a "recognition" state under the tumor acidic microenvironment for efficient tumor cellular uptake due to the direct exposure of active targeting ligand HA following PEG shell detachment. Such a transformative concept provides a promising strategy to resolve the dilemma of natural ligand-based DDS with conflicting two processes of tumor cellular uptake and in vivo nonspecific biodistribution.展开更多
Challenges associated with low-drug-loading capacity,lack of active targeting of tumor cells and unspecific drug release of nanocarriers synchronously plague the success of cancer therapy.Herein,we constructed active-...Challenges associated with low-drug-loading capacity,lack of active targeting of tumor cells and unspecific drug release of nanocarriers synchronously plague the success of cancer therapy.Herein,we constructed active-targeting,redox-activated polymeric micelles(HPGssML)selfassembled aptamer-decorated,amphiphilic biodegradable poly(benzyl malolactonate-co-e-caprolactone)copolymer with disulfide linkage and p-conjugated moieties.HPGssML with a homogenous spherical shape and nanosized diameter(-150 nm)formed a low critical micellar concentration(10^-3mg/mL),suggesting good stability of polymeric micelles.The anticancer drug,doxorubicin(DOX),can be efficiently loaded into the core of micelles with high-drug-loading content via strong π-π interaction,which was verified by a decrease in fluorescence intensity and redshift in UV adsorption of DOX in micelles.The redox sensitivity of polymeric micelles was confirmed by size change and in vitro drug release in a reducing environment.Confocal microscopy and flow cytometry assay demonstrated that conjugating aptamers could enhance specific uptake of HPGssML by cancer cells.An in vitro cytotoxicity study showed that the half-maximal inhibitory concentration(IC50)of DOX-loaded HPGssML was two times lower than that of the control group,demonstrating improved antitumor efficacy.Therefore,the multifunctional biodegradable polymeric micelles can be exploited as a desirable drug carrier for effective cancer treatment.展开更多
基金Supported by National Key Research and Development program(MOST 2022YFA1602304)the National Natural Science Foundation of China(12335009,U1632142,12505146).
文摘We measured the^(19)O+^(12)C fusion excitation function using the MATE active-target TPC at IMP for 9.7≤Ec.m.≤16.9 MeV.The results agree well with DC-TDHF and TDHF predictions,demonstrating the importance of dynamical effects near the barrier,but disagree with earlier MUSIC-based measurements.The^(19)O+^(12)C system exhibits a maximum fusion cross section consistent with those ofβ-stable O+C systems.A linear dependence of 1/E_(cr) and closest-approach distance on oxygen mass number is observed for^(17,18,19)O+^(12)C,indicating that additional valence neutrons lower the critical energy.V-shaped excitation structures appear for^(17)O and^(19)O,and the anomalous suppression previously reported for^(17)O calls for further experimental and theoretical study.
基金supported by the National Basic Research Program of China(No.81573371)the Key Projects of Liaoning Province Department of Education(No.2017LZD03,China)
文摘Hyaluronic acid(HA) is a natural ligand of tumor-targeted drug delivery systems(DDS) due to the relevant CD44 receptor overexpressed on tumor cell membranes. However, other HA receptors(HARE and LYVE-1) are also overexpressing in the reticuloendothelial system(RES). Therefore,polyethylene glycol(PEG) modification of HA-based DDS is necessary to reduce RES capture.Unfortunately, pegylation remarkably inhibits tumor cellular uptake and endosomal escapement,significantly compromising the in vivo antitumor efficacy. Herein, we developed a Dox-loaded HA-based transformable supramolecular nanoplatform(Dox/HCVBP) to overcome this dilemma. Dox/HCVBP contains a tumor extracellular acidity-sensitive detachable PEG shell achieved by a benzoic imine linkage.The in vitro and in vivo investigations further demonstrated that Dox/HCVBP could be in a "stealth" state at blood stream for a long circulation time due to the buried HA ligands and the minimized nonspecific interaction by PEG shell. However, it could transform into a "recognition" state under the tumor acidic microenvironment for efficient tumor cellular uptake due to the direct exposure of active targeting ligand HA following PEG shell detachment. Such a transformative concept provides a promising strategy to resolve the dilemma of natural ligand-based DDS with conflicting two processes of tumor cellular uptake and in vivo nonspecific biodistribution.
基金supported by the Natural Science Foundation of China(Grant No.51973135)National Key Research and Development Program of China(Grant Nos.2018YFC1106103,2017YFB0702600,2017YFB0702603)Science and Technology Foundation of Sichuan Province(Grant No.2018RZ0044).
文摘Challenges associated with low-drug-loading capacity,lack of active targeting of tumor cells and unspecific drug release of nanocarriers synchronously plague the success of cancer therapy.Herein,we constructed active-targeting,redox-activated polymeric micelles(HPGssML)selfassembled aptamer-decorated,amphiphilic biodegradable poly(benzyl malolactonate-co-e-caprolactone)copolymer with disulfide linkage and p-conjugated moieties.HPGssML with a homogenous spherical shape and nanosized diameter(-150 nm)formed a low critical micellar concentration(10^-3mg/mL),suggesting good stability of polymeric micelles.The anticancer drug,doxorubicin(DOX),can be efficiently loaded into the core of micelles with high-drug-loading content via strong π-π interaction,which was verified by a decrease in fluorescence intensity and redshift in UV adsorption of DOX in micelles.The redox sensitivity of polymeric micelles was confirmed by size change and in vitro drug release in a reducing environment.Confocal microscopy and flow cytometry assay demonstrated that conjugating aptamers could enhance specific uptake of HPGssML by cancer cells.An in vitro cytotoxicity study showed that the half-maximal inhibitory concentration(IC50)of DOX-loaded HPGssML was two times lower than that of the control group,demonstrating improved antitumor efficacy.Therefore,the multifunctional biodegradable polymeric micelles can be exploited as a desirable drug carrier for effective cancer treatment.
