Stimuli-responsive drug delivery systems based on polymeric micelles can achieve controlled drug release to improve the therapeutic outcome and reduce unwanted systematic toxicity and side effects of the cytotoxic dru...Stimuli-responsive drug delivery systems based on polymeric micelles can achieve controlled drug release to improve the therapeutic outcome and reduce unwanted systematic toxicity and side effects of the cytotoxic drug in chemotherapy but often face challenging synthesis and purification of functionalized biocompatible polymer materials and low drug loading efficiency. In the present study, we reported a novel redox-responsive self-assembly polymeric micelle system, mPEG-β-CD/Ad-SS-CPT, to achieve high loading efficiency and selective delivery of camptothecin(CPT) in a reductive environment inside cancer cells. The host-guest supramolecular micelles utilized a simple β-CD modified PEG, mPEG-β-cyclodextrin(mPEG-β-CD), as the polymeric host with the ease of synthesis and purification. The guest prodrug Ad-SS-CPT contained the disulfide bond as the redox sensitivity group. The selective cleavage of disulfide bond and subsequent drug release in a reductive environment could potentially reduce system toxicity and improve the therapeutic outcome of CPT. In vitro studies showed that the micelles exhibited excellent cytotoxicity against He La cells comparable to the free drug. The host-guest polymeric micelles also showed great potentials for multi-drug co-delivery. Collectively, our current findings provided a general and convenient approach to design drug delivery systems based on stimuli-responsive polymeric micelles for disease treatment.展开更多
Nonlinear vibration with axisymmetric 3:1 internal resonance is investigated for an incompressible neo-Hookean hyperelastic cylindrical shell under both axial and radial harmonic excitations.A full nonlinear strain-di...Nonlinear vibration with axisymmetric 3:1 internal resonance is investigated for an incompressible neo-Hookean hyperelastic cylindrical shell under both axial and radial harmonic excitations.A full nonlinear strain-displacement relation is derived from the large deflection theory of thin-walled shells.A set of nonlinear differential equations describing the large deflection vibration are formulated by the Lagrange equation and the assumption of small strains.Steady-state responses of the system are predicted via the harmonic balance method with the arc length continuation,and their stabilities are determined via the modified sorting method.The effects of excitations on the steady-state responses are analyzed.The results reveal a crucial role played by the phase difference in the structural response,and the phase difference can effectively control the amplitude of vibration.展开更多
基金National Key Research and Development Program of China (Grant No. 2019YFA0904800)Science and Technology Commission of Shanghai Municipality (Grant No. 11DZ2260600 and 10DZ2220500)Shanghai Natural Science Fund (Grant No. 20ZR1414700)。
文摘Stimuli-responsive drug delivery systems based on polymeric micelles can achieve controlled drug release to improve the therapeutic outcome and reduce unwanted systematic toxicity and side effects of the cytotoxic drug in chemotherapy but often face challenging synthesis and purification of functionalized biocompatible polymer materials and low drug loading efficiency. In the present study, we reported a novel redox-responsive self-assembly polymeric micelle system, mPEG-β-CD/Ad-SS-CPT, to achieve high loading efficiency and selective delivery of camptothecin(CPT) in a reductive environment inside cancer cells. The host-guest supramolecular micelles utilized a simple β-CD modified PEG, mPEG-β-cyclodextrin(mPEG-β-CD), as the polymeric host with the ease of synthesis and purification. The guest prodrug Ad-SS-CPT contained the disulfide bond as the redox sensitivity group. The selective cleavage of disulfide bond and subsequent drug release in a reductive environment could potentially reduce system toxicity and improve the therapeutic outcome of CPT. In vitro studies showed that the micelles exhibited excellent cytotoxicity against He La cells comparable to the free drug. The host-guest polymeric micelles also showed great potentials for multi-drug co-delivery. Collectively, our current findings provided a general and convenient approach to design drug delivery systems based on stimuli-responsive polymeric micelles for disease treatment.
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.11672069,11872145,11872159,12172086,and 12101106).
文摘Nonlinear vibration with axisymmetric 3:1 internal resonance is investigated for an incompressible neo-Hookean hyperelastic cylindrical shell under both axial and radial harmonic excitations.A full nonlinear strain-displacement relation is derived from the large deflection theory of thin-walled shells.A set of nonlinear differential equations describing the large deflection vibration are formulated by the Lagrange equation and the assumption of small strains.Steady-state responses of the system are predicted via the harmonic balance method with the arc length continuation,and their stabilities are determined via the modified sorting method.The effects of excitations on the steady-state responses are analyzed.The results reveal a crucial role played by the phase difference in the structural response,and the phase difference can effectively control the amplitude of vibration.
