Latest ArticlesThe last few decades have witnessed the emergence of a very large variety of engineered nanomaterials. However, it is far from to meet the growing clinical demand. Actually, nature itself is an excellent nanotechnologist, and provides us with a range of wonderful materials, from inorganic particles found in non-life bodies to biofilms, like platelets, erythrocyte membranes, produced by many bacteria or cells. These nanomaterials are entirely natural, and not surprisingly, there is a growing interest in the development of natural nanoproducts. Native components-inspired biomaterials have gained considerable attention owing to their safety and functions. In this study, egg white was developed as drug carrier to load PTX by a green and simple one-pot method, and systematic characterization was completed. The results indicated that PTX@EW NPs possess excellent biocompatibility, enhanced tumor targeting capability, effectively reducing the toxic side effects of PTX. The obviously enhanced antitumor effect further confirmed EW was a highly prospective biomaterial in the nano-carrier industry.
Quaternary ammonium salts (QASs) are excellent candidates for treating stubborn bacterial infections caused by biofilms due to their high sterilization efficiency and potential inhibition of the development of drug resistance. However, the inherent toxicity of QASs, including cytotoxicity, protein absorption and hemolysis, severely limits their applications in vivo. Herein, a charge-convertible quaternary ammonium salt-based micelle (QAS-SL@CM) was constructed by co-assembly of two amphiphiles with opposite charges and shell cross-linking strategy. The toxicity of the QAS-SL@CM could be greatly reduced towards human cells contrast to the corresponding QASs. By response to the acidic environment at infection sites, the surface charge of QAS-SL@CM could be immediately changed to positive and then target to negatively charged bacteria. Furthermore, β-thiopropionate bonds on QAS-SL@CM could also be disintegrated under acid environment to release QASs to kill bacteria. Importantly, the QAS-SL@CM showed significant therapeutic effect in mice subcutaneous abscesses models without interference with normal cells. Therefore, a surface adaptive micelle constructed by charge-convertible strategy has been developed to overcome the cytotoxicity of QASs, and could intelligently respond to the microenvironment of infected wound for in vivo infection therapy, which shows promising application in clinic.
The improvement in accuracy of in vitro diagnosis has always been the focus of early screening of thyroid dysfunction. We constructed a microfluidic chip based on a polystyrene polymer substrate. Total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3), free thyroxine (FT4), and thyrotropin (TSH) in human whole blood samples were analysed by fluorescence immunoassay to evaluate thyroid function. The results indicate that the microfluidic chip shows a good linear relationship in the detection of TT3, TT4, FT3, FT4, and TSH standards, and the correlation coefficient (r) is not less than 0.9900. In addition, the chip also has strong anti-interference (RSD% ≤ 5%) and good repeatability (CV ≤ 8%), and its inter-batch differences are small (CV ≤ 15%). The results of practical application in clinical thyroid function measurement indicated its high accuracy (r ≥ 0.9900). It provides a new method for the determination of thyroid function and lays a foundation for subsequent clinical application.
Although the antitumor drug cabazitaxel shows great therapeutic potential, its high toxicity and poor water solubility limit its utility. However, the use of stimuli-responsive prodrugs is a promising strategy for overcoming these limitations. Herein, we report the synthesis of two highly water soluble, acid-sensitive PEGylated acyclic-ketal-linked cabazitaxel prodrugs (PKCs) with improved antitumor efficacy. In an acidic tumor microenvironment, the PKCs hydrolyzed rapidly to release the native drug, whereas they were stable in the normal physiological environment. Compared with cabazitaxel injection, the PKCs had much higher maximum tolerated doses; and in an MDA-MB-231 subcutaneous xenograft nude mouse model, the PKCs showed better antitumor efficacy and safety than cabazitaxel injection. The prodrug strategy reported herein could be useful for the development of other water soluble, acid-sensitive prodrugs with improved efficacy.
Fragrances are frequently added to a variety of products, including food, cosmetics and health products. However, the high volatility and instability of essence limit its application in some fields. In this study, mesoporous silica nanoparticles (MSNs) were prepared to encapsulate eugenol, which could reduce the volatilization of the fragrance molecules. A facile approach was presented to synthesize MSNs with three different pore diameters for encapsulating eugenol. In addition, the properties of MSNs including mean particle size, morphology, encapsulating efficiency and release tendency were characterized. Results showed that the larger the pore diameters of MSNs, the more aromatic molecules were adsorbed. Furthermore, the release mechanism was described as the smaller the pore diameters of MSNs, the slower the release of eugenol.
The increasing incidence of osteoarthritis (OA) seriously affects life quality, posing a huge socioeconomic burden. Tissue engineering technology has become a hot topic in articular cartilage repair as one of the key treatment methods to alleviate OA. Hydrogel, one of the most commonly used scaffold materials, can provide a good extracellular matrix microenvironment for seed cells such as bone marrow mesenchymal stem cells (BMSCs), which can promote cartilage regeneration. However, the low homing rate of stem cells severely limits their role in promoting articular cartilage regeneration. Stromal cell-derived factor- 1α (SDF-1α) plays a crucial role in the activation, mobilization, homing, and migration of MSCs. Herein, a novel injectable chemotaxis hydrogel, composed of chitosan-based injectable hydrogel and embedding SDF-1α-loaded nanodroplets (PFP@NDs-PEG-SDF-1α) was designed and fabricated. The ultrasound was then used to augment the injectable chemotaxis hydrogel and promote the homing migration of BMSCs for OA cartilage repair. The effect of ultrasound augmenting injectable PFP@NDs-PEG-SDF-1α/hydrogel on the migration of BMSCs was verified in vitro and in vivo, which remarkably promotes stem cell homing and the repair of cartilage in the OA model. Therefore, the treatment strategy of ultrasound augmenting injectable chemotaxis hydrogel has a bright potential for OA articular cartilage repair.
Nanomaterial based drug delivery system have received great attention in clinical application due to their high therapeutic efficacy and lower side effects than classical method, multi-functional nanomaterial also have shown the excellent performance at cancer theranostic and durg tracking in vivo and in vitro. However, most of these works are influenced by the bio-toxicity of applied nanomaterials, which could influence the diagnostic results and treatment effect. Therefore, we have prepared a high biocompatibility porous carbon nanospheres (PCNs) based nano-system (PCN-siRNA-DOX-FA) for targeted drug delivery and theranostic. The surface modifications have increased dispersion and stability of the PCNs, and folic acid (FA) had enhanced the active target ability for FA receptor positive cell lines. Moreover, through the siRNA structure and doxorubicin (DOX) loading, biological and chemical combined multi-therapy was achieved in cancerous cells. This constructed nano-system could positively improve the biotoxicity problem of nanomaterial and provide a potential platform for clinical cancer theranostic applications.
Despite of the promising achievements of immune checkpoints blockade therapy (ICB) in the clinic, which was often limited by low objective responses and severe side effects. Herein, we explored a synergistic strategy to combine in situ vaccination and gene-mediated anti-PD therapy, which was generated by unmethylated cytosine-phosphate-guanine (CpG) and pshPD-L1 gene co-delivery. PEI worked as the delivery carrier to co-deliver the CpG and pshPD-L1 genes, the formed PDC (PEI/DNA/CpG) nanoparticles were further shielded by aldehyde modified polyethylene glycol (OHC-PEG-CHO) via pH responsive Schiff base reaction for OHC-PEG-CHO-PEI/DNA/CpG nanoparticles (P(PDC) NPs) preparation. All steps could be finished within 30 min. Such simple nanoparticles achieved the synergistic antitumor efficacy in B16F10 tumor-bearing mice, and the amplified T cell responses, together with enhanced NK cells infiltration were observed after the combined treatments. In addition, the pH responsive delivery system reduced the side effects triggered by anti-PD therapy. The facile and effective combination strategy we presented here might provide a novel treatment for tumor inhibition.
Recently, stimuli-responsive DNA nanostructure-based nanodevices have been applied for cancer therapy. In this study, pH-responsive i-motif DNA was modified on gold nanoparticles (AuNPs) via a facile, time-saving freeze-thaw method and utilized to construct stimuli-responsive drug nanocarriers. When the environment pH changes from 7.4 to 5.0, the i-motif DNA would be folded into four-stranded (C-quadruplex) that could be characterized by circular dichroism, and the characteristic of acid stimulate was verified by fluorescence resonance energy transfer (FRET). To enhance specifical cellular uptake, MUC1 aptamer was employed as the targeting moiety. Doxorubicin (Dox) is an anticancer drug that can be efficiently intercalated into GC base pairs of DNA nanostructure to form drug-loaded nanovehicles (Dox@AuNP-MUC1). Additionally, owing to the excellent photothermal conversion efficiency of AuNPs, the synergistic effect between chemotherapy and PTT can be readily achieved by 808 nm near-infrared (NIR) irradiation, which exhibits specifically and efficiently anticancer efficiency. Hence, this multifunctional drug carrier shows the potential for synergistic photothermal-chemotherapy.
Traditional colorimetric glucose biosensor generally involves complex assay procedures. Free labile enzymes and peroxidase substrates are used separately for triggering a chromogenic reaction. These limits result in inferior enzyme stability and defective enzymatic catalytic efficiency, making it hard to routinely utilize them for the direct and fast test of glucose. In this work, we provide an all-inclusive substrates/enzymes nanoparticle employed 3, 3'5, 5'-tetramethylbenzidine (TMB) as chromogenic substrates and glucose oxidase (GOx)/horseradish peroxidase (HRP) as signal amplifier enzymes (TMB-GH NPs) by the molecule self-assembly technique. The "all-inclusive" nanoparticles can realize the tandem colorimetric reactions, and the oxidation product of TMB (ox-TMB) exhibits a strong NIR laser-driven photothermal effect, thus allowing quantitative photothermal detection of glucose. Owing to the restriction of the molecular motion of GOx, HRP, and TMB, the distance of mass transfer between substrates was shortened largely, leading to improved catalytic activity for glucose. Overall, our strategy will simplify the analysis procedure, furthermore, these integrated nanoparticles not only display higher stability and activity than that of the free GOx/HRP system and possesses an excellent performance for colorimetric and photothermal bioassay of glucose simultaneously. We believe that this unique technique will give good inspirations to develop simple and precise methods for bioassay.
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