Strain localization of Mohr-Coulomb soils with non-associated plasticity based on micropolar continuum theory

To address the problems of strain localization, the exact Mohr-Coulomb (MC) model is used based on second-order cone programming (mpcFEM-SOCP) in the framework of micropolar continuum finite element method. Using the uniaxial compression test, we focused on the earth pressure problem of rigid wall segment involving non-associated plasticity. The numerical results reveal that when mpcFEM-SOCP is applied, the problems of mesh dependency can be effectively addressed. For geotechnical strain localization analysis involving non-associated MC plasticity, mpcFEM-SOCP in conjunction with the pseudo-time discrete scheme can improve the numerical stability and avoid the unreasonable softening issue in the pressure-displacement curves, which may be encountered in the conventional FEM. It also shows that the pressure-displacement responses calculated by mpcFEM-SOCP with the pseudo-time discrete scheme are higher than those calculated by mpcFEM-SOCP with the Davis scheme. The inclination angle of shear band predicted by mpcFEM-SOCP with the pseudo-time discrete scheme agrees well with the theoretical solution of non-associated MC plasticity.

Synthesis and evaluation of a paclitaxel-binding polymeric micelle for efficient breast cancer therapy

Paclitaxel(PTX) is one of the most effective anticancer drugs for the treatment of various solid tumors, but its clinical use is limited by its poor solubility, low bioavailability, and severe systemic toxicity. Encapsulation of PTX in polymeric nanoparticles is used to overcome these problems but these micelles still need improvements in stability, pharmacokinetics, therapeutic efficacy, and safety profiles. In this study, we demonstrate a facile fabrication of a stable PTX-binding micelle made from poly(ethylene glycol)-block-dendritic polylysine, whose primary amines were reacted with phenethyl isothiocyanate(PEITC), a hydrophobic anticancer agent under clinical study. The amphiphilic conjugate(PEG-Gx-PEITC; Gx, the generation of the polylysine dendron) formed well-defined micelles whose core was composed of phenyl groups and thiourea groups binding PTX via π-π stacking and hydrogen bonding. Compared with the PTX-loaded poly(ethylene glycol)-block-poly(D,L-lactide)(PEGPDLLA/PTX) micelles in clinical use, PTX-loaded PEG-Gx-PEITC third-generation(PEG-G3-PEITC/PTX) micelles showed slowed blood clearance, enhanced tumor accumulation, and thus much improved in vivo therapeutic efficacy in both subcutaneous and orthotopic human breast cancer xenografts. Therefore, PEG-G3-PEITC is a promising drug delivery system for PTX in the treatment of breast cancer.

Injectable kartogenin and apocynin loaded micelle enhances the alleviation of intervertebral disc degeneration by adipose-derived stem cell

Cell transplantation has been proved the promising therapeutic effects on intervertebral disc degeneration(IVDD).However,the increased levels of reactive oxygen species(ROS)in the degenerated region will impede the efficiency of human adipose-derived stem cells(human ADSCs)transplantation therapy.It inhibits human ADSCs proliferation,and increases human ADSCs apoptosis.Herein,we firstly devised a novel amphiphilic copolymer PEG-PAPO,which could self-assemble into a nanosized micelle and load lipophilic kartogenin(KGN),as a single complex(PAKM).It was an injectable esterase-responsive micelle,and showed controlled release ability of KGN and apocynin(APO).Oxidative stimulation promoted the esterase activity in human ADSCs,which accelerate degradation of esterase-responsive micelle.Compared its monomer,the PAKM micelle possessed better bioactivities,which were attributed to their synergistic effect.It enhanced the viability,autophagic activation(P62,LC3 II),ECM-related transcription factor(SOX9),and ECM(Collagen II,Aggrecan)maintenance in human ADSCs.Furthermore,it is demonstrated that the injection of PAKM with human ADSCs yielded higher disc height and water content in rats.Therefore,PAKM micelles perform promoting cell survival and differentiation effects,and may be a potential therapeutic agent for IVDD.

Engineering molecular self-assembly of theranostic nanoprobes for dual-modal imaging-guided precise chemotherapy

Uniting dual-modality of fluorescence and photoacoustic(PA)imaging into theranostic nanoprobes is imperative for spatiotemporally tracking of drug delivery,distribution,and release.Herein,we present a rational design strategy of molecularly precise amphiphilic prodrugs BP_(n)-Cy-S-CPT(n=0,5,and 20,refers to the degree of polyethylene glycol(PEG)polymerization;CPT=camptothecin)to tune their self-assembly behaviour,innovatively integrating dual-modal PA and near-infrared(NIR)fluorescence imaging in a single-molecular framework.Among these elaborately designed prodrugs,it is found that only BP_(20)-Cy-S-CPT could form uniform and highly stable self-assemblies,especially in showing synergistically enhanced PA and dualchannel NIR signals.In detail,PA signal is employed to trace the in vivo delivery with high spatial resolution,meanwhile the glutathione(GSH)-triggered dual-channel fluorescence response could real-timely monitor drug distribution and release without"blind spot".The results of in vivo dual-modal PA/NIR imaging have verified that BP_(20)-Cy-S-CPT displayed synergistic targeting(including passive,active,and activatable targeting)for tumor-specific delivery,and thereby executed CPT release in the tumor site.Consequently,our molecularly precise BP_(20)-Cy-S-CPT self-assemblies could make a breakthrough to spatiotemporally track the in vivo drug release profile,expanding the intelligent theranostic toolbox for precise cancer treatment.