Advances in oral mesenchymal stem cell-derived extracellular vesicles in health and disease

Extracellular vesicles(EVs)are nano-size vesicles secreted naturally by all cells into the extracellular space and have been recognized as important cell-cell mediators in multicel-lular organisms.EVs contain nucleic acids,proteins,lipids,and other cellular components,regulating many basic biological processes and playing an important role in regenerative med-icine and diseases.EVs can be traced to their cells of origin and exhibit a similar function.Moreover,EVs demonstrate low immunogenicity,good biocompatibility,and fewer side ef-fects,compared to their parent cells.Mesenchymal stem cells(MsCs)are one of the most important resource cells for EVs,with a great capacity for self-renewal and multipotent differ-entiation,and play an essential role in stem cell therapy.The mechanism of MsC therapy was thought to be attributed to the differentiation of MsCs after targeted migration,as previously noted.However,emerging evidence shows the previously unknown role of MsC-derived para-crine factors in stem cell therapy.Especially EVs derived from oral tissue MSCs(OMSC-EVs),show more advantages than those of all other MsCs in tissue repair and regeneration,due to their lower invasiveness and easier accessibility for sample collection.Here,we systematically review the biogenesis and biological characteristics of OMSC-EVs,as well as the role of OMsC-EVs in intercellular communication.Furthermore,we discuss the potential therapeutic roles of OMSC-EVs in oral and systemic diseases.We highlight the current challenges and future directions of OMSC-EVs to focus more attention on clinical translation.We aim to provide valuable insights for the explorative clinical application of OMSC-EVs.

抗原改造联合纳米肿瘤疫苗用以克服肿瘤新抗原短缺及在多种肿瘤类型上激起强效抗肿瘤免疫反应

Neoantigen cancer vaccines have been envisioned as one of the most promising means for cancer therapies.However,identifying neoantigens for tumor types with low tumor mutation burdens continues to limit the effectiveness of neoantigen vaccines.Herein,we proposed a "hit-and-run" vaccine strategy which primes T cells to attack tumor cells decorated with exogenous "neo-antigens".This vaccine strategy utilizes a peptide nanovaccine to elicit antigen-specific T cell responses after tumor-specific decoration with a nanocarrier containing the same peptide antigens.We demonstrated that a poly(2-oxazoline)s(POx) conjugated with OVA_(257-264) peptide through a matrix metalloprotease 2(MMP-2) sensitive linker could efficiently and selectively decorate tumor cells with OVA peptides in vivo.Then,a POx-based nanovaccine containing OVA_(257-264) peptides to elicit OVA-specific T cell responses was designed.In combination with this hit-and-run vaccine system,an effective vaccine therapy was demonstrated across tumor types even without OVA antigen expression.This approach provides a promising and uniform vaccine strategy against tumors with a low tumor mutation burden.

Targeted nanostrategies eliminate pre-metastatic niche of cancer

Establishing a pre-metastatic niche(PMN)in secondary organs is a prerequisite for cancer metastases.Despite advances in cancer therapy,the efficient inhibition of PMN formation remains a clinical challenge.Recent advances in understanding the specific characteristics of PMN and advances in nanotechnology have provided hope for manipulating their microenvironments.A series of nanostrategies have been designed to eliminate the PMN,including the removal of pro-metastatic exosomes from the bloodstream for excretion via the intestines,the targeting and scavenging of myeloid-derived suppressor cells,fibroblasts,and critical extracellular matrix components,and the elimination of circulating tumor cells prior to colonization in distant organs.This review summarizes the underlying mechanisms of PMN formation,highlights the anti-PMN efficacy of currently reported nanostrategies,and underlines the unresolved questions.

Poly(Ethylene Oxide) Mediated Synthesis of Sub-100-nm Aluminum Nanocrystals for Deep Ultraviolet Plasmonic Nanomaterials

Aluminum nanocrystals(Al NCs)are sustainable plasmonic nanomaterials with unique localized surface plasmonic resonance(LSPR)in the ultraviolet(UV)region.Chemical synthesis of sub-100-nm Al NCs remains a considerable challenge due to the lack of effective ligands to control their growth.Here,we describe a precise size-controlled synthesis of small colloidal Al NCs(25–100 nm)with strong and tunable LSPR peak from 250 to 372 nmin the UV spectral region by the use of poly(ethylene oxide)(PEO)as a polydentate surface ligand.

Gold Nanoparticle Enantiomers and Their Chiral-Morphology Dependence of Cellular Uptake

Chiral molecules are widely prevalent in nature and biological systems,and artificial chiral nanoparticles have drawn enormous interest owing to their unique optical and physical properties.However,nanoparticles with chiral morphologies and their potential role in biology have been rarely explored.Herein,we report a seed-mediated synthesis of enantiomorphic Au nanooctopods(NOPs)and their chiralmorphology dependence of cellular uptake.With a high yield(∼80%),the chiral NOPs possess eight uniform arms that bend from<111>to<100>directions,like a propeller structure.The chiral NOPs synthesized with L-or D-glutathione(GSH)have opposite handedness,resulting in opposite circular dichroism signals,which is consistent with finite-difference time-domain simulations.D-GSH NOPs demonstrate greater than 30%(ca.15%)enhanced cellular uptake in GL261 and bEnd.3 cells compared with L-GSH NOPs(racemic NOPs).Moreover,D-GSH NOPs modified with poly(ethylene glycol)or L-GSH are also preferred by the cells,proving the chiral-morphology dependence of cellular uptake.Our study develops the exploration of the chiral-specific interaction in biological systems,providing potential applications for drug delivery,biosensing,and tumor detection.

Multiresponsive Polymer Assemblies Achieved by a Subtle Chain Terminal Modification

Inspired by the influence of chemical structure of end groups on the phase transition temperature of thermoresponsive polymers,we demonstrated a strategy to control the multi-responsiveness of polymer assemblies via subtle modification of end groups of thermoresponsive polymer segments and revealed its potential application for drug delivery.By developing polymer assemblies composed of poly(aliphatic ester) as the inner core and thermoresponsive polyphosphoester as the outer shell,we showed that end groups of thermoresponsive polyphosphoester segments controlled the surface property of assemblies and further determined the stimuli-responsive behavior.The phase-transition temperatures of the unmodified polymer assemblies are tightly controlled by their surface properties due to the hydrophilic to hydrophobic transitions of end groups in response to an environmental stimulus (e.g.pH or light irradiation).External control over these surface properties can by asserted by adjusting the chemical structure and composition of the terminal groups of the thermoresponsive polyphosphoesters.