Search

CircRNAs are newly identified special endogenous RNA molecules that covalently close a loop by back-splicing with pre-mRNA. In the cytoplasm, circRNAs would act as molecular sponges to bind with specific miRNA to promote the expression of target genes. However, knowledge of circRNA functional alternation in skeletal myogenesis is still in its infancy. In this study, we identified a circRNA–miRNA–mRNA interaction network in which the axis may be implicated in the progression of chicken primary myoblasts’ (CPMs) myogenesis by multi-omics (i.e., circRNA-seq and ribo-seq). In total, 314 circRNA–miRNA–mRNA regulatory axes containing 66 circRNAs, 70 miRNAs, and 24 mRNAs that may be relevant to myogenesis were collected. With these, the circPLXNA2-gga-miR-12207-5P-MDM4 axis aroused our research interest. The circPLXNA2 is highly differentially expressed during differentiation versus proliferation. It was demonstrated that circPLXNA2 inhibited the process of apoptosis while at the same time stimulating cell proliferation. Furthermore, we demonstrated that circPLXNA2 could inhibit the repression of gga-miR-12207-5p to MDM4 by directing binding to gga-miR-12207-5p, thereby restoring MDM4 expression. In conclusion, circPLXNA2 could function as a competing endogenous RNA (ceRNA) to recover the function of MDM4 by directing binding to gga-miR-12207-5p, thereby regulating the myogenesis.

Exploiting zeolitic imidazolate framework (ZIF)-based nanoparticles to synergistically enhance starvation-combined chemotherapy strategies remains an urgent demand. Herein, glucose oxidase (GOX) and doxorubicin (DOX) were facilely incorporated into ZIFs for starvation-combined chemotherapy. The as-prepared DOX/GOX-loaded ZIF (DGZ) exhibited uniform size with good dispersity, effective protection of the GOX activity, and stable delivery of the drugs into tumor. Correspondingly, it could achieve the glucose- and pH-responsive degradation and thus the controllable drug release. As a result, the acidification of glucose accompanied with reactive oxygen species (ROS) production was observed for the starvation-enhanced chemotherapy and the improved degradation. Most importantly, adjustable Zn

Functionalization of mesoporous silica spheres with well-dispersed and ultra-small nanodots to exert their synergistic effects for biomedical applications has been considered to be an urgent challenge. Herein, homogeneously incorporation of ultra-small and monodispersed MoS2 nanodots in the mesoporous silica nanospheres (MSN) was achieved by a facile one-step solvothermal reaction. The as-synthesized UsMSND@MSN possessed uniform size (∼115 nm) and favorable biocompatibility inherited from MSN. The dispersed UsMSND within MSN could act as anchoring sites for aromatic anti-cancer drug DOX loading, and consequently achieved pH-responsive release based on the special π-π/electrostatic interactions with the DOX molecules. More importantly, the well-dispersed UsMSND in MSN could function as the non-toxic contrast agent for the sensitive in vivo CT imaging in various tumors including breast cancer and glioma with different sections. This work promises a good strategy for dispersed incorporation of UsMSND into MSN as an excellent pH-responsive platform for simultaneous cancer imaging and therapy.

Diabetes immunity-modulated wound treatment in response to the varied microenvironments at different stages remains an urgent challenge. Herein, glucose oxidase (GOx) and quasi-amorphous Fesub2/subOsub3/subare co-incorporated into Zn-MOF nanoparticle (F-GZ) for cascade enzyme catalytic activities, where not only the high blood glucose in the wound is consumed via the GOx catalysis, but also the effective anti-bacteria is achieved via the degradedly released Znsup2+/supsynergistically with the catalytically produced ·OH during the bacterial infection period with the low pH microenvironment. Simultaneously, the reactive oxygen species scavenging and hypoxia relief is realized via catalyzing Hsub2/subOsub2/subto produce Osub2/subat the relatively elevated pH environment during the wound recovery period. Subsequently, a multifunctional hydrogel with injectable, self-healing and hemostasis abilities, as well as uniformed F-GZ loading is prepared via the copolymerization reaction. This hydrogel behaves as F-GZ but reduces the toxic effects, which thus accelerates the diabetic wound healing. More importantly, this hydrogel is found to modulate the diabetes immunity possibly mediated via the released Znsup2+/sup, which thus contributes to the recovered pancreatic islet functions with improved glucose tolerance and increased insulin secretion for enhanced diabetic wound treatments. This work initiates a new strategy for simultaneous diabetic wound management and also suggests a potential way for diabetic immunity modulation.

Incorporating carbon nanodots (CDs) into mesoporous silica framework for extensive biomedicine, especially for the desirable cancer immunotherapy, is considered to be an unexplored challenge. Herein, a hydrogen bond/electrostatic-assisted co-assembly strategy was smartly exploited to uniformly incorporate polymer-coated CDs into ordered framework of mesoporous silica nanoparticles (CD@MSNs). The obtained CD@MSN was not only biodegradable via the framework-incorporated CD-induced swelling but also capable of gathering dispersive CDs with enhanced photothermal effect and elevated targeting accumulation, which therefore can achieve photothermal imaging-guided photothermal therapy (PTT) in vitro and in vivo. Interestingly, benefiting from the biodegraded debris, it was found that CD@MSN-mediated PTT can synergistically achieve immune-mediated inhibition of tumor metastasis via stimulating the proliferation and activation of natural killer cells and macrophages with simultaneously up-regulating the secretion of corresponding cytokines (IFN-γ and Granzyme B). This work proposed an unusual synthesis of biodegradable mesoporous silica and provided an innovative insight into the biodegradable nanoparticles-associated anticancer immunity.

Fibroblast activation protein-alpha (FAPα) is a key modulator of the microenvironment in multiple pathologies and is becoming the next pan-cancer target for cancer diagnostics and therapeutics. Chemiluminescence (CL) luminophores are considered as one of the most sensitive families of probes for detection and imaging applications due to their high signal-to-noise ratio. Until now, however, no such effective CL probe was reported for FAPα detection. Herein, we developed a novel CL probe for the detection of endogenous FAPα activity by incorporating FAPα-specific dipeptide substrates (glycine-proline) to the improved Schaap's adamantylidene-dioxetane. In this manner, we designed three CL probes (CFCL, BFCL, and QFCL) with the dipeptide substrate blocked by N-terminal benzyloxycarbonyl, N-tert-butoxycarbonyl or N-quinoline-4-carboxylic acid, respectively, which was used as the masking group to restrain the chemiexcitation energy. Probe CFCL exhibited the optimal specificity for the discrimination of FAPα from dipeptidase IV and prolyl oligopeptidase, which was elucidated by molecular docking simulation. Upon FAPα cleavage, CFCL was turned on for the highly selective and sensitive detection of FAPα with a limit of detection of 0.785 ng/mL. Furthermore, the ability of CFCL to image FAPα was effectively demonstrated in vitro, including various biological samples (plasma and tissue preparations), and in living systems (tumor cells and tumor-bearing mice). Furthermore, this newly established probe could be easily extended to evaluate FAPα inhibitors. Overall, we anticipate that probe CFCL will offer a facile and cost-effective alternative in the early detection of pathologies, individual tailoring of drug therapy, and drug screening.

Integrating multiple discrete function-related theranostic modalities into one platform for effective cancer treatments has been considered to be a challenge for current nanomedicine design. In this work, a "four-in-one" theranostic system was simply prepared and developed for photoacoustic (PA) imaging-guided synergistic targeting chemo-gene-thermo trimodal therapy of breast cancer. In this system, polyethylene glycol (PEG)-bridged polyethylenimine (PEI) and a memHsp70 receptor-targeting peptide (TKD), PPT, was uniformly capped on doxorubicin (DOX)-loaded oxidized mesoporous carbon nanospheres (OMCN) to encapsulate therapeutic genes into cancer cells via active targeting accumulation. Taking both the advantages of OMCN (high photothermal conversion, strong PA contrast, and controllable drug loading) and the hydrophilic polymer (gene vector, switchable pores' cap, and targeting ability), the "four-in-one" theranostic system exhibited distinct PA imaging visualization, NIR/pH sensitive drug/gene release, and synergistic targeting therapeutic outcome, which were much superior than the single therapy or the combination of two treatments.

Covalent organic framework (COF) nanoparticles for interference-free targeted drug delivery to glioma remains in its infancy. Herein, hollow COF nanospheres with high crystallinity and uniformed sizes were facilely prepared via heterogeneous nucleation-growth. The prepared COF had large surface area/pore volume and exhibited appropriate degradation behavior under acid environment, where therefore doxorubicin was effectively encapsulated and exhibited a pH-sensitive release. Most charmingly, T10 peptide that has high affinity with transferrin (Tf), was conjugated to endow the hollow COF interesting properties to specifically absorb Tf in vivo as Tf corona. For the first time, multifunctional hollow COF nanospheres (the better one named DCPT-2) were successfully synthesized to achieve interference-free cascade-targeting glioma drug delivery across the blood-brain barrier. Treatment with DCPT-2 brought an improved therapeutic outcome with significantly prolonged median survival time and low side effects. This work promised not only a potential protein corona-mediated COF-based drug delivery platform with good biocompatibility for effective and precise brain tumor therapy, but also an endogenous protein corona-mediated targeting strategy for general cancer therapy.

Developing an all-in-one multimodal theranostic platform that can synergistically integrate sensitive photoacoustic (PA) imaging, enhanced photothermal therapy (PTT) and photodynamic therapy (PDT) as well as the nano-enzyme activated chemodynamic therapy (CDT) presents a great challenge for the current nanomedicine design. Herein, a simple hydrothermal method was used to prepare porous molybdenum disulfide (MoS

The development of drug delivery vehicles without side effects to normal physiological tissues represents an urgent challenge for safety and effective nanomedicine. Herein, a multifunctional drug delivery vehicle with ultralow leakage was presented, containing an ordered mesoporous resin as a polymer core and homogeneous Fe nanodots-doped silica as the biodegradable shell. In this core-shell structure, the Fe-doped silica shell acts as a compact inorganic cap to seal doxorubicin into the mesoporous polymer cores, but also serves as a superparamagnetic agent for magnetic targeting and magnetic resonance imaging (MRI). Importantly, the caps can be opened via Fe extraction-induced degradation to slowly release the loaded drug under the acidic tumor environment, while achieving ultralow drug leakage under normal in vivo blood circulation (physiological environment). This unique core-shell nanospheres with ultralow drug leakage were demonstrated to achieve side effects-avoided targeting chemotherapy guided by MRI with improved therapeutic outcomes, which showing great potential for efficient cancer theranostics.

Overcoming blood-brain barrier (BBB) for precise glioma diagnosis remains an urgent challenge due to its peculiar location in central nervous system (CNS). Herein, polymer-coated carbon nanodots with high hydrophilicity were facilely married with Gd-DTPA to construct a dual-modal imaging system (NCDDG). This system was demonstrated with obviously decreased toxicity and enhanced magnetic resonance imaging (MRI) ability compared to traditional Gd-DTPA. Meanwhile, NCDDG reserved the bright fluorescence of biocompatible carbon nanodots with increased spatial resolution. Attributed to small size and hydrophilic polymer coating, NCDDG was capable of overcoming the BBB and permeating leaky microvascular walls into surrounding glioma tissues via prolonged in vivo circulation and enhanced retention effect. As a result, dual1-modal targeted MR/fluorescence imaging of glioma was synergistically achieved with high sensitivity and resolution. This work promised a potential contrast agent for sensitive clinical diagnosis of glioma.

Imaging-guided site-specific photothermal therapy (PTT) of glioma and other tumors in central nervous system presents a great challenge for the current nanomaterial design. Herein, an in situ solid-state transformation method was developed for the preparation of multicolor highly crystalline carbon nanodots (HCCDs). The synthesis yields 6-8 nm-sized HCCDs containing a highly crystalline carbon nanocore and a hydrophilic surface, which therefore simultaneously provide strong photoacoustic and photothermal performances as well as tunable fluorescence emission. In vitro and in vivo results demonstrate that the novel HCCDs have high water dispersity and good biocompatibility, but potent tumor cell killing upon near-infrared irradiation. As demonstrated in U87 glioma-bearing mice, HCCDs specifically accumulate in brain tumors and facilitate dual-modal imaging-guided PTT, with therapeutic antitumoral effects without any apparent damage to normal tissues.

Overcoming biological barriers to imaging-guided site-specific delivery of therapeutics is the goal of current nanomedicine designs. Here, multifunctional polymer-coated carbon nanodots with an interleukin-6 (IL-6) fragment peptide for receptor-targeting (pCDPI) were prepared for drug delivery. The pCDPI exhibits small hydrodynamic diameters, high water solubility and biocompatibility. In vitro and in vivo results demonstrated that pCDPI can overcome the blood-brain barrier (BBB) and deeply penetrate into orthotopic glioma in mice, to inhibit IL-6-induced cell proliferation and achieve imaging-guided targeted drug delivery. Simultaneously, a pH-sensitive sustained release of doxorubicin (DOX) accompanied with real-time fluorescence monitoring was realized. A distinct synergistic therapeutic outcome could be achieved which suggests the presented nanomedicine having promising potential for future cancer treatments.

© Ivyspring International Publisher. In this report, we present a mesoporous carbon nanosphere that can target drugs to tumors and image tumor biomarkers. A single-strand DNA (P0aptamer) aptavalve was capped on the surface of doxorubicin-loaded oxide mesoporous carbon nanospheres (Dox-OMCN-P0) through p-p stacking for real-time imaging-guided on-demand targeting drug delivery. The Dox-OMCN-P0could not only realize the detection of MUC1 tumor marker with a wide linear range (0.1 - 10.6 μmol/L) and a low detection limit (17.5 nmol) based on different apparatuses, but also achieve in-situ targeting imaging of cellular MUC1 concentration in vitro and in vivo via "off-on" fluorescence biosensing. Much attractively, as a real-time feedback of the diagnostic/imaging outcomes, Dox-OMCN-P0accomplished the on-demand targeting drug delivery in quantitative response to MUC1. Controllable chemotherapy with sustained release and pH-sensitiveness, together with the potential photothermal therapy, were also clearly demonstrated. This is a simple but advanced platform, which could well achieve the real-time switchable imaging of cellular mucin for targeting cancer therapy.

The effective treatment of glioma is largely hindered by the poor transfer of drug delivery systems across the blood-brain barrier (BBB) and the difficulty in distinguishing healthy and tumorous cells. In this work, for the first time, an interleukin-6 receptor binding I6P7 peptide was exploited as a cascade-targeting ligand in combination with a succinoyl tetraethylene pentamine (Stp)-histidine oligomer-based nonviral gene delivery system (I6P7-Stp-His/DNA). The I6P7 peptide provides multiple functions, including the cascade-targeting potential represented by a combined BBB-crossing and subsequent glioma-targeting ability, as well as a direct tumor-inhibiting effect. I6P7-Stp-His/DNA nanoparticles (NPs) mediated higher gene expression in human glioma U87 cells than in healthy human astrocytes and a deeper penetration into glioma spheroids than scrambled peptide-modified NPs. Transport of I6P7-modified, but not the control, NPs across the BBB was demonstrated in vitro in a transwell bEnd.3 cell model resulting in transfection of underlying U87 cells and also in vivo in glioma-bearing mice. Intravenous administration of I6P7-Stp-His/plasmid DNA (pDNA)-encoding inhibitor of growth 4 (pING4) significantly prolonged the survival time of orthotopic U87 glioma-bearing mice. The results denote that I6P7 peptide is a roborant cascade-targeting ligand, and I6P7-modified NPs might be exploited for efficient glioma therapy.

Nowadays there are more and more rare material-based tumor-targeted systems such as black phosphorus-based tumor-targeted systems, upconversion nanoparticle-based tumor-targeted systems, reactive oxygen and nitrogen species (RONS) scavenger-based tumor-targeted systems, perfluorocarbon nanoparticles, sulfide-based tumor-targeted systems, oxide-based tumor-targeted systems, and biomimetic material-based tumor-targeted systems. The properties of the systems are mostly dependent on the specialties of materials. This chapter will introduce both the materials and systems and focus on the targeting efficiency, bioactivity, and the relating mechanisms of killing tumor cells and inhibiting the progress of tumor growth.

Gene therapy is a rapidly emerging remedial route for many serious incurable diseases, such as central nervous system (CNS) diseases. Currently, nucleic acid medicines, including DNAs encoding therapeutic or destructive proteins, small interfering RNAs or microRNAs, have been successfully delivered to the CNS with gene delivery vectors using various routes of administration and have subsequently exhibited remarkable therapeutic efficiency. Among these vectors, non-viral vectors are favorable for delivering genes into the CNS as a result of their many special characteristics, such as low toxicity and pre-existing immunogenicity, high gene loading efficiency and easy surface modification. In this review, we highlight the main types of therapeutic genes that have been applied in the therapy of CNS diseases and then outline non-viral gene delivery vectors.

Blocking the tumor energy metabolism is expected to be a potential cancer treatment strategy. However, developing a single and simple nanoparticle system to directly block the tumor energy metabolism with good biosafety and high potential for clinical application remains absence. Herein, a technique is described for the preparation of sugar-originated carbon nanodots (sCND) which is inspired by the traditional cooking skill of pork braised in brown sauce, where the sucrose caramelizes in the hot vegetable oil. The special preparation endows sCND with some glucose residues on their surfaces and optical nanodot properties, which enable the GLUT1-mediated glioma-targeted accumulation that can be monitored by in vivo imaging. Subsequently, sCND can hamper the avid uptake of glucose into the tumor. This blocks the tumor energy metabolism, impairs tumor growth and enhances sensitivity to chemotherapy as shown in two tumor models (glioma and hepatoma). Additionally, this kind of carbon nanodots possesses a favorable biosafety profile, including low cytotoxicity, almost no hematotoxicity and tissue damaging potential. It is edible due to the special preparation and structure similar to the traditional cooking style. This work reports a simple method to produce advanced therapeutic carbon nanodots with favorable biodistribution and biosafety, which will pave the way for a powerful platform with future clinical applications.

Dispersed incorporation of functional nanoparticles into ordered mesopores to exert their synergistic properties has shown a promising application, but proved to be a challenging task. Herein, a facile strategy based on solid-phase transformation of the template into polymer-coated carbonaceous nanodots (pCNDs) is used for direct synthesis of multifunctional mesoporous silica nanospheres (MFMSNs) incorporated with dispersed fluorescent carbon nanodots. The homogeneous pCNDs incorporated into mesoporous silica nanospheres (MSNs) can simultaneously act as the nontoxic fluorescence probe for highly efficient fluorescence imaging and also anchoring sites for anticancer drug loading. On the basis of the special hydrophobic π–π/electrostatic interaction between the confined pCNDs in MFMSNs and the aromatic drug molecules, MFMSNs could also function as an advanced drug carrier for pH-triggered drug release. The very simple strategy suggests new insights for synthesizing multifunctional mesoporous nanomaterials and extends the biomedical functions of traditional MSN-based nanovehicles for future biomedical applications.

Due to the poor self-regeneration of brain tissue, stem cell transplantation therapy is purported to enable the replacement of lost neurons after traumatic brain injury (TBI). The main challenge of brain regeneration is whether the transplanted cells can survive and carry out neuronal functions in the lesion area. The brain is a complex neuronal network consisting of various types of cells that significantly influence on each other, and the survival of the implanted stem cells in brain is critically influenced by the surrounding cells. Although stem cell-based therapy is developing rapidly, most previous studies just focus on apply single type of stem cells as cell source. Here, we found that co-culturing human umbilical cord mesenchymal stem cells (hUC-MSCs) directly with the activated astrocytes benefited to the proliferation and neuron differentiation of hUC-MSCs in vitro. In this study, hUC-MSCs and the activated astrocytes were seeded in RADA16-BDNF peptide scaffold (R-B-SPH scaffold), a specifical self-assembling peptide hydrogel, in which the environment promoted the differentiation of typical neuron-like cells with neurites extending in three-dimensional directions. Moreover, the results showed co-culture of hUC-MSCs and activated astrocytes promoted more BDNF secretion which may benefit to both neural differentiation of ectogenic hUC-MSCs and endogenic neurogenesis. In order to promote migration of the transplanted hUC-MSCs to the host brain, the hUC-MSCs were forced with CXC chemokine receptor 4 (CXCR4). We found that the moderate-sized lesion cavity, but not the large cavity caused by TBI was repaired via the transplantation of hUC-MSCs CXCR4 and activated astrocytes embedded in R-B-SPH scaffolds. The functional neural repair for TBI demonstrated in this study is mainly due to the transplantation system of double cells, hUC-MSCs and activated astrocytes. We believe that this novel cell transplantation system offers a promising treatment option for cell replacement therapy for TBI. Statement of Significance In this reach, we specifically linked RGIDKRHWNSQ, a functional peptide derived from BDNF, to the C-terminal of RADARADARADARADA (RADA16) to structure a functional self-assembling peptide hydrogel scaffold, RADA16-BDNF (R-B-SPH scaffold) for the better transplantation of the double cell unit. Also, the novel scaffold was used as cell-carrier for transplantation double cell unit (hUC-MSCs/astrocyte) for treating traumatic brain injury. The results of this study showing that R-B-SPH scaffold was pliancy and flexibility to fit the brain lesion cavity and promotes the outgrowth of axons and dendrites of the neurons derived from hUC-MSCs in vitro and in vivo, indicating the 3D R-B-SPH scaffold provided a suitable microenvironment for hUC-MSC survival, proliferation and differentiation. Also, our results showing the double-cells transplantation system (hUC-MSCs/astrocyte) may be a novel cell-based therapeutic strategy for neuroregeneration after TBI with potential value for clinical application.

Combining controllable photothermal therapy and efficacious gene therapy in a single platform holds great promise in cancer therapy due to the enhanced combined therapeutic effects. Herein, polyethyleneimine-grafted oxidized mesoporous carbon nanospheres (OP) were developed for combined photothermal combined gene therapy in vitro and in vivo. The synthesized OP was characterized to have three dimensional spherical structure with uniformed diameter, ordered mesopores with graphitic domains, high water dispersion with zeta potential of +22 mV, and good biocompatibility. Consequently, OP was exploited as the photothermal convertor with strong NIR absorption and the gene vector via electrostatic interaction, which therefore cannot only deliver the therapeutic gene (pING4) to tumors for gene therapy, but also can eliminate the tumors by photothermal ablation. Moreover, the improved gene therapy accompanied by the NIR photothermally enhanced gene release was also well achieved based on OP. The excellent combined therapeutic effects demonstrated in vitro and in vivo suggested the OP's potential for cancer therapy.

Developing an all-in-one multimodal theranostic platform that can synergistically integrate sensitive photoacoustic (PA) imaging, enhanced photothermal therapy (PTT) and photodynamic therapy (PDT) as well as the nano-enzyme activated chemodynamic therapy (CDT) presents a great challenge for the current nanomedicine design. Herein, a simple hydrothermal method was used to prepare porous molybdenum disulfide (MoS2) nanoflowers. These nanoflowers were assembled by three dimensional (3D)-stacked MoS2 nanosheets with plentiful pores and large surfaces, which thus exhibited enhanced photothermal conversion via light trapping and peroxidase (POD)-like activity via active defects exposure. Consequently, this 3D-MoS2 nanostructure could be well-sealed by polyethylene glycol-polyethylenimine polymer modified with nucleolar translocation signal sequence of the LIM Kinase 2 protein (LNP) via strong electrostatic interaction, which not only benefited to stably deliver anticancer drug doxorubicin (DOX) into the tumor cells for pH/NIR-responsive chemotherapy, but also provided strong photoacoustic, photothermal performances and stimulated generation of reactive oxygen species (ROS) for imaging-guided PTT/PDT/CDT combined therapy. This work promised a simple all-in-one multimodal theranostic platform to augment the potential antitumoral therapeutic outcomes.

Glioma has been considered to be the most frequent primary tumor within central nervous system (CNS). The complexity of glioma, especially the existence of blood-brain barrier (BBB), makes the survival and prognosis of glioma remain poor even after a standard treatment based on the standard therapy (surgery combined with radiotherapy or chemotherapy). This provides a rationale for the development of some novel therapeutic strategies. Among them, receptor-mediated drug delivery is a specific pattern taking advantage of differential expression of receptors between tumors and normal tissues. The strategy can actively transport drugs such as small molecular drugs, gene medicines, and therapeutic proteins to glioma while minimizing adverse reactions. Besides, adsorptive-mediated, transporter-mediated process, or nasal pathway are also widely studied strategies. This review will summarize recent progresses on glioma targeted drug delivery systems based on several main mechanisms and conclude the challenges and prospects of these glioma targeted systems for future applications.

Functionalizing black phosphorus nanosheet (BP) with efficient drug loading and endowing mesoporous silica nanomaterials with appropriate biodegradation for controllable tumor-targeted chemo-photothermal therapy are still urgent challenges. Herein, an ordered mesoporous silica-sandwiched black phosphorus nanosheet (BP@MS) with the vertical pore coating was prepared. The strategy could not only enhance the BP's dispersity and improve its doxorubicin (DOX)-loading efficiency, but also facilitate post-modification such as PEGylation and conjugation of targeting ligand, TKD peptide, yielding BSPT. A DOX-loaded BSPT-based system (BSPTD) showed heat-stimulative, pH-responsive, and sustained release manners. In vitro and in vivo results demonstrated that BSPTD had a delayed but finally complete degradation in physiological medium, contributing to an optimal therapeutic window and good biosafety. As a result, BSPTD can achieve an effective chemo-photothermal synergistic targeted therapy of tumor. Moreover, treating by BSPTD was found to be capable of remarkably inhibiting the lung metastasis of tumor, attributing to the photothermal degradation-facilitated secondary drug delivery. Our study provided a robust strategy to functionalize BP nanosheet and biodegrade the mesoporous silica for extended biomedical applications.

Overcoming blood-brain barrier (BBB) for precise glioma diagnosis remains an urgent challenge due to its peculiar location in central nervous system (CNS). Herein, polymer-coated carbon nanodots with high hydrophilicity were facilely married with Gd-DTPA to construct a dual-modal imaging system (NCDDG). This system was demonstrated with obviously decreased toxicity and enhanced magnetic resonance imaging (MRI) ability compared to traditional Gd-DTPA. Meanwhile, NCDDG reserved the bright fluorescence of biocompatible carbon nanodots with increased spatial resolution. Attributed to small size and hydrophilic polymer coating, NCDDG was capable of overcoming the BBB and permeating leaky microvascular walls into surrounding glioma tissues via prolonged in vivo circulation and enhanced retention effect. As a result, dual

Accumulating studies have investigated the efficacy of receptor-mediated delivery of hydrophobic drugs in glioma chemotherapy. Here, a delivery vehicle comprising polyethylene glycol (PEG) and oxidized nanocrystalline mesoporous carbon particles (OMCN) linked to the Pep22 polypeptide targeting the low-density lipoprotein receptor (LDLR) is designed to generate a novel drug-loaded system, designated as OMCN-PEG-Pep22/DOX (OPPD). This system effectively targets glioma cells and the blood-brain barrier and exerts therapeutic efficacy through both near-infrared (NIR) photothermal and chemotherapeutic effects of loaded doxycycline (DOX). Pathological tissue microarrays show an association of LDLR overexpression in human glioma tissue with patient survival.NIR irradiation treatment and magnetic resonance imaging results show that OPPD reaches the effective glioma-killing temperature in a glioma-bearing rat with a skull bone removal model and considerably reduces glioma sizes relative to the drug-loaded system without the Pep22 peptide modification and the control respectively. Thus, OPPD not only effectively targets LDLR-overexpressing glioma but also exerts a dual therapeutic effect by transporting DOX into the glioma and generating thermal effects with near-infrared irradiation to kill tumor cells. These collective findings support the utility of the novel OPPD drug-loaded system as a promising drug delivery vehicle for clinical application in glioma therapy.

Breast cancer has been considered as a serious threat to females' life. Active targeting drug delivery is a potential strategy in cancer therapy, which however is hindered by the targeting efficiency. Herein, a 14-mer peptide (TKD) derived from the oligomerization domain of membrane heat-shock protein 70 (memHsp70), for the first time, was exploited as a tumor-targeting ligand to modify polymeric micelles. NMR results demonstrated the successful synthesis of TKD-PEG-PLGA polymer. No difference was observed in the drug release between TKD-modified doxorubicin (DOX)-loaded micelles (TKD-D-M) and unmodified counterparts. The modification of TKD mediated apparently higher cellular uptake within memHsp70-positive MCF-7 cells, compared to normal MCF-10A cells. Excessive TKD pretreatment significantly inhibited the cellular uptake of TKD-D-M, indicating the receptor-mediated mechanism. Enhanced accumulation of TKD-D-M within the tumor of MCF-7 bearing mice further demonstrated the targeting ability of TKD in vivo. CCK-8 assay showed that the modification of TKD significantly increase the anti-proliferation effect against MCF-7 cells. The findings demonstrated that TKD peptide is a potential ligand which can target drug delivery systems to memHsp70-positive breast cancer.

A facile one-step solvothermal method was developed for the homogeneously confined growth of ultra-small (∼1.5 nm) and monodispersed 2H phase MoS2 nanodots into mesoporous silica nanoparticles (MSNs).

Multiple diagnosis of cancer by a facile fluorescent sensor is extremely attractive. Herein, a Cy3-labeled ssDNA probe (P0-Cy3) was π-π stacked on the surface of oxidized mesoporous carbon nanospheres (OMCN) to construct the fluorescent "turn-on" aptasensor. Attributing to the intrinsic properties of OMCN, the OMCN-based aptasensor not only can be used to detect mucin1 protein in liquid with a wide range of 0.1-10.6 μmol/L, a low detection limit of 6.52 nmol/L, and good selectivity, but also can quantify the cancer cells in solution with the linear range of 10(4)-2 × 10(6) cells/mL and a detection limit of 8500 cells/mL. Fascinatingly, this OMCN-based aptasensor was exploited to image cancer via solid tissues such as cells, tissue sections, and ex vivo and in vivo tumors, in which the obvious distinguishability between cancer and normal tissues was clearly demonstrated. This is a robust and simple detection technique, which can well achieve the multiple diagnosis of cancer in vitro and in vivo.

Successful glioma gene therapy lays on two important factors, the therapeutic genes and efficient delivery vehicles to cross the blood-brain barrier (BBB) and reach gliomas. In this work, a new gene vector was constructed based on dendrigraft poly-l-lysines (DGL) and polyethyleneglycol (PEG), conjugated with a cell-penetrating peptide, the nucleolar translocation signal (NoLS) sequence of the LIM Kinase 2 (LIMK2) protein (LIMK2 NoLS peptide, LNP), yielding DGL-PEG-LNP. Plasmid DNA encoding inhibitor of growth 4 (ING4) was applied as the therapeutic gene. DGL-PEG-LNP/DNA nanoparticles (NPs) were monodispersed, with a mean diameter of 90.6 ± 8.9 nm. The conjugation of LNP significantly enhanced the BBB-crossing efficiency, cellular uptake and gene expression within tumor cells. Mechanism studies suggested the involvement of energy, caveolae-mediated endocytosis and macropinocytosis in cellular uptake of LNP-modified NPs. MTT results showed that no apparent cytotoxicity was observed when cells were treated with synthesized vectors. Furthermore, LNP-modified NPs mediated strongest and most intensive apoptosis on the tumor site, and the longest median survival time of glioma-bearing mice. All the results demonstrated that LNP is a kind of efficient CPPs especially for BBB-crossing application, and DGL-PEG-LNP/DNA is a potential non-viral platform for glioma gene therapy via intravenous administration.

Bimetallic nanocatalysts often display enhanced physical and chemical properties compared to those of their monometallic counterparts. Herein, we introduce a simple method to fabricate an island like array of tiny Ag nanoparticles bounded on triangular Au nanoplates as the surface-enhanced Raman scattering (SERS) substrate. The surface morphology of the synthesized nanoparticles was characterized via field emission scanning electron microscopy (FE-SEM), and atomic force microscopy (AFM). Rhodamine 6G (R6G) is used as a model analyte to evaluate the performance of the tiny Ag nanoparticle bounded triangular Au nanoplates as a SERS-active substrate and validate the SERS effect. The fabricated SERS substrate showed drastically enhanced intensity with a SERS enhancement factor as high as 107, which is enough to detect a single molecule, and excellent reproducibility (less than ±5%) of the signal intensity. This is because of the island-like tiny Ag nanoparticle bounded triangular Au nanoplates and their large number of “hot spots”. This substrate could also be used for label-free immunoassays, biosensing, and nanoscale optical antennas and light sources.

Tumor site-directed multifunctional therapeutic platforms such as photothermochemotherapy that respond to tumor-focused physical and biological stimuli are highly demanded for effective cancer therapy. Herein, targeting peptide-conjugated core–shell graphitic carbon@silica nanospheres with dual-ordered mesopores (MMPS) were successfully fabricated and developed as antitumoral doxorubicin (DOX) delivery system (MMPSD) for synergistic targeted photothermal chemotherapy of breast cancer. The hydrophilic mesoporous silica shell guarantees good water dispersity of MMPSD. The hydrophobic graphitic mesoporous carbon core provides excellent hydrophobic drug loading, immediate contact between the drug and photothermal hotspots, and high NIR photothermal conversion efficiency. SP13 peptide facilitates MMPSD for targeted and enhanced delivery of DOX within HER2-positive SK-BR-3 breast cancer cells, while PEGylation ensures biocompatibility. Thus, the MMPSD system exhibited efficient drug loading capacity, high targeting ability, sensitive NIR/pH-responsive DOX release, sustained release, and excellent combined antitumor activity.

Targeting peptide-modified magnetic graphene-based mesoporous silica (MGMSPI) are synthesized, characterized, and developed as a multifunctional theranostic platform. This system exhibits many merits, such as biocompatibility, high near-infrared photothermal heating, facile magnetic separation, large T2 relaxation rates (r2), and a high doxorubicin (DOX) loading capacity. In vitro and in vivo results demonstrate that DOX-loaded MGMSPI (MGMSPID) can integrate magnetic resonance imaging, dual-targeting recognition (magnetic targeting and receptor-mediated active targeting), and chemo-photothermal therapy into a single system for a visualized-synergistic therapy of glioma. In addition, it is observed that the MGMSPID system has heat-stimulated, pH-responsive, sustained release properties. All of these characteristics would provide a robust multifunctional theranostic platform for visualized glioma therapy.

To prepare an angiopep-conjugated dendrigraft poly-L-lysine (DGL)-based gene delivery system and evaluate the neuroprotective effects in the rotenone-induced chronic model of Parkinson’s disease (PD). Angiopep was applied as a ligand specifically binding to low-density lipoprotein receptor-related protein (LRP) which is overexpressed on blood-brain barrier (BBB), and conjugated to biodegradable DGL via hydrophilic polyethyleneglycol (PEG), yielding DGL-PEG-angiopep (DPA). In vitro characterization was carried out. The neuroprotective effects were evaluated in a chronic parkinsonian model induced by rotenone using a regimen of multiple dosing intravenous administrations. The successful synthesis of DPA was demonstrated via 1H-NMR. After encapsulating the therapeutic gene encoding human glial cell line-derived neurotrophic factor (hGDNF), DPA/hGDNF NPs showed a sphere-like shape with the size of 119 ± 12 nm and zeta potential of 8.2 ± 0.7 mV. Angiopep-conjugated NPs exhibited higher cellular uptake and gene expression in brain cells compared to unmodified counterpart. The pharmacodynamic results showed that rats in the group with five injections of DPA/hGDNF NPs obtained best improved locomotor activity and apparent recovery of dopaminergic neurons compared to those in other groups. This work provides a practical non-viral gene vector for long-term gene therapy of chronic neurodegenerative disorders.