Linear-like polypeptide-based micelle with pH-sensitive detachable PEG to deliver dimeric camptothecin for cancer therapy

Nano drug delivery systems have made significant progress in delivering anticancer drugs camptothecin(CPT).However,many challenges for CPT delivery remain,including low drug loading efficiency,premature drug leakage,and poor cellular internalization.Herein,we report a novel dual-sensitive polypeptide-based micelle with remarkably high drug loading of CPT for cancer therapy.This self-assembled micelle possesses the following essential components for CPT:(1)pH-sensitive PEG(OHC-PEG-CHO)for prolonging blood circulation and allowing biocompatibility by shielding the cationic micelles,which can be detached under the tumor acidic microenvironment and facilitates the cellular uptake;(2)polypeptide polylysine-polyphenylalanine(PKF)synthesized via ring-opening polymerization for micelle formation and CPT analogue loading;(3)dimeric CPT(DCPT)with redox-sensitive linker for increasing CPT loading and ensuring drug release at tumor sites.Interestingly,the linear-like morphology of PEG-PKF/DCPT micelles was able to enhance their cellular internalization when compared with the spherical blank PKF micelles.Also,the anticancer efficacy of DCPT against lung cancer cells was significantly improved by the micelle formation.In conclusion,this work provides a promising strategy facilitating the safety and effective application of CPT in cancer therapy.

Research on the Prevention and Control of the Internet Rumor from the Perspective of the Self-Media

With the rapid development of Internet science and technology, the self-media industry is rising gradually. As an important way of information dissemination, more and more self-media platforms are established and the main body of information communication becomes more complex. The self-media not only brings convenience to people’s life but also brings some negative effects. The self-media has more remarkable characteristics in information dissemination. The birth of self-media makes the network appear more suspicious information that cannot be effectively verified. Internet rumors fly all over the sky, which has caused certain influence on the stability of the society. The prevention and control measures of online rumors from the perspective of self-media are studied in this paper for creating a healthier network environment. Firstly, the concepts of self-media and Internet rumors are briefly summarized. Then, the main characteristics of Internet rumors from the perspective of self-media are analyzed. Finally, the prevention and control measures of online rumors, including strengthening supervision, improving the quality of self-media, and strengthening public identification of rumors, are proposed.

Reversing the imbalance in bone homeostasis via sustained release of SIRT-1 agonist to promote bone healing under osteoporotic condition

The imbalance of bone homeostasis is the root cause of osteoporosis.However current therapeutic approaches mainly focus on either anabolic or catabolic pathways,which often fail to turn the imbalanced bone metabolism around.Herein we reported that a SIRT-1 agonist mediated molecular therapeutic strategy to reverse the imbalance in bone homeostasis by simultaneously regulating osteogenesis and osteoclastogenesis via locally sustained release of SRT2104 from mineral coated acellular matrix microparticles.Immobilization of SRT2104 on mineral coating(MAM/SRT)harnessing their electrostatic interactions resulted in sustained release of SIRT-1 agonist for over 30 days.MAM/SRT not only enhanced osteogenic differentiation and mineralization,but also attenuated the formation and function of excessive osteoclasts via integrating multiple vital upstream signals(β-catenin,FoxOs,Runx2,NFATc1,etc.)in vitro.Osteoporosis animal model also validated that it accelerated osteoporotic bone healing and improved osseointegration of the surrounding bone.Overall,our work proposes a promising strategy to treat osteoporotic bone defects by reversing the imbalance in bone homeostasis using designated small molecule drug delivery systems.

A trilogy antimicrobial strategy for multiple infections of orthopedic implants throughout their life cycle

Bacteria-associated infection represents one of the major threats for orthopedic implants failure during their life cycles.However,ordinary antimicrobial treatments usually failed to combat multiple waves of infections during arthroplasty and prosthesis revisions etc.As these incidents could easily introduce new microbial pathogens in/onto the implants.Herein,we demonstrate that an antimicrobial trilogy strategy incorporating a sophisticated multilayered coating system leveraging multiple ion exchange mechanisms and fine nanotopography tuning,could effectively eradicate bacterial infection at various stages of implantation.Early stage bacteriostatic effect was realized via nano-topological structure of top mineral coating.Antibacterial effect at intermediate stage was mediated by sustained release of zinc ions from doped CaP coating.Strong antibacterial potency was validated at 4 weeks post implantation via an implanted model in vivo.Finally,the underlying zinc titanate fiber network enabled a long-term contact and release effect of residual zinc,which maintained a strong antibacterial ability against both Staphylococcus aureus and Escherichia coli even after the removal of top layer coating.Moreover,sustained release of Sr2+and Zn2+during CaP coating degradation substantially promoted implant osseointegration even under an infectious environment by showing more peri-implant new bone formation and substantially improved bone-implant bonding strength.

PDGFR in PDGF-BB/PDGFR Signaling Pathway Does Orchestrates Osteogenesis ina Temporal Manner

Platelet-derived growth factor-BB(PDGF-BB)/platelet-derived growth factor receptor-β(PDGFR-β)pathway is conventionally considered as an important pathway to promote osteogenesis;however,recent study suggested its role during osteogenesis to be controversial.Regarding the differential functions of this pathway during 3 stages of bone healing,we hypothesized that temporal inhibition of PDGF-BB/PDGFR-βpathway could shift the proliferation/differentiation balance of skeletal stem and progenitor cells,toward osteogenic lineage,which leads to improved bone regeneration.We first validated that inhibition of PDGFR-βat late stage of osteogenic induction effectively enhanced differentiation toward osteoblasts.This effect was also replicated invivo by showing accelerated bone formation when block PDGFR-βpathway at late stage of critical bone defect healing mediated using biomaterials.Further,we found that such PDGFR-βinhibitor-initiated bone healing was also effective in the absence of scaffold implantation when administrated intraperitoneally.Mechanistically,timely inhibition of PDGFR-βblocked extracellular regulated protein kinase 1/2 pathway,which shift proliferation/differentiation balance of skeletal stem and progenitor cell to osteogenic lineage by upregulating osteogenesis-related products of Smad to induce osteogenesis.This study offered updated understanding of the use of PDGFR-βpathway and provides new insight routes of action and novel therapeutic methods in the field of bone repair.