Albumin Nanoparticles Increase the Efficacy of Doxorubicin Hydrochloride Liposome Injection Based on Threshold Theory.

One of the most significant reasons hindering the clinical translation of nanomedicines is the rapid clearance of intravenously injected nanoparticles by the mononuclear phagocyte system, particularly by Kupffer cells in the liver, leading to an inefficient delivery of nanomedicines for tumor treatment. The threshold theory suggests that the liver's capacity to clear nanoparticles is limited, and a single high dose of nanoparticles can reduce the hepatic clearance efficiency, allowing more nanomedicines to reach tumor tissues and enhance therapeutic efficacy. Building upon this theory, researchers have conducted numerous validation studies based on the same nanoparticle carrier systems. These studies involve the use of albumin nanoparticles to improve the therapeutic efficacy of albumin nanomedicines as well as polyethylene glycol (PEG)-modified liposomal nanoparticles to enhance the efficacy of PEGylated liposomal nanomedicines. However, there is no research indicating the feasibility of the threshold theory when blank nanoparticles and nanomedicine belong to different nanoparticle carrier systems currently. In this study, we prepared two different sizes of albumin nanoparticles by using bovine serum albumin. We used the marketed nanomedicine liposomal doxorubicin hydrochloride injection (trade name: LIBOD, manufacturer: Shanghai Fudan-zhangjiang Biopharmaceutical Co., Ltd.), as the representative nanomedicine. Through in vivo experiments, we found that using threshold doses of albumin nanoparticles still can reduce the clearance rate of LIBOD, prolong its time in vivo, increase the area under the plasma concentration-time curve (AUC), and also lead to an increased accumulation of the drug at the tumor site. Furthermore, evaluation of in vivo efficacy and safety further indicates that threshold doses of 100 nm albumin nanoparticles can enhance the antitumor effect of LIBOD without causing harm to the animals. During the study, we found that the particle size of albumin nanoparticles influenced the in vivo distribution of the nanomedicine at the same threshold dose. Compared with 200 nm albumin nanoparticles, 100 nm albumin nanoparticles more effectively reduce the clearance efficiency of LIBOD and enhance nanomedicine accumulation at the tumor site, warranting further investigation. This study utilized albumin nanoparticles to reduce hepatic clearance efficiency and enhance the delivery efficiency of nonalbumin nanocarrier liposomal nanomedicine, providing a new avenue to improve the efficacy and clinical translation of nanomedicines with different carrier systems.

Preparation of Liposome Gel by Calcium Cross-Linking Induces the Long-Term Release of DOX to Improve the Antitumor Effect.

Doxorubicin (DOX) is one of the most commonly used anticancer drugs; however, its clinical application is greatly limited due to its toxicity and chemotherapy resistance. The delivery of DOX by liposomes (Lipos) can improve the blood circulation time in vivo and reduce toxic side effects, but the drug's accumulation in the tumor is often insufficient for effective treatment. In this study, we present a calcium cross-linked liposome gel for the encapsulation of DOX, demonstrating its superior long-term release capabilities compared to conventional Lipos. By leveraging this enhanced long-term release, we can enhance drug accumulation within tumors, ultimately leading to improved antitumor efficacy. Lipos were prepared using the thin-film dispersion method in this study. We utilized the ion-responsiveness of glutathione-gelatin (GSH-GG) to form the gel outside the Lipos and named the nanoparticles coated with GSH-GG on the outside of Lipos as Lipos@GSH-GG. The average size of Lipos@GSH-GG was around 342.9 nm, with a negative charge of -25.6 mV. The in vitro experiments revealed that Lipos@GSH-GG exhibited excellent biocompatibility and slower drug release compared to conventional Lipos. Further analysis of cellular uptake and cytotoxicity demonstrated that Lipos@GSH-GG loading DOX (DOX&Lipos@GSH-GG) exhibited superior long-term release effects and lower toxic side effects compared to Lipos loading DOX (DOX&Lipos). Additionally, the findings regarding the long-term release effect in vivo and the tumor accumulation within tumor-bearing mice of Lipos@GSH-GG suggested that, compared to Lipos, it demonstrated superior long-term release capabilities and achieved greater drug accumulation within tumors. In vivo antitumor efficacy experiments showed that DOX&Lipos@GSH-GG demonstrated superior antitumor efficacy to DOX&Lipos. Our study highlights Lipos@GSH-GG as a promising nanocarrier with the potential to enhance efficacy and safety by means of long-term release effects and may offer an alternative approach for effective antitumor therapy in the future.

Enhanced effect of a novel bioactive glass-ceramic for dental application.

OBJECTIVES: Dental caries is the most common chronic disease in humans, caused by the acid produced by the microflora in the mouth that dissolves the enamel minerals. Bioactive glass (BAG) has been used in various clinical applications due to its unique bioactive properties, such as bone graft substitutes and dental restorative composites. In this study, we introduce a novel bioactive glass-ceramic (NBGC) prepared through a sol-gel process under a water-free condition. MATERIALS AND METHODS: The anti-demineralization and remineralization effects of NBGC were evaluated by comparing the measurements of bovine enamel surface morphology, surface roughness, surface micro-hardness, enamel elements, and mineral content before and after related treatments with a commercial BAG. The antibacterial effect was characterized by minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). RESULTS: Results showed that NBGC had greater acid resistance and remineralization potential compared to commercial BAG. The fast formation of a hydroxy carbonate apatite (HCA) layer suggests efficient bioactivity. CLINICAL RELEVANCE: In addition to its antibacterial properties, NBGC shows promise as an ingredient in oral care products that can prevent demineralization and restore enamel.

Modulation of Aggregation-Caused Quenching to Aggregation-Induced Emission: Finding a Biocompatible Polymeric Theranostics Platform for Cancer Therapy.

Dual intramolecular FRET polymers are synthesized via Suzuki coupling and their luminescence characteristics from aggregation-caused quenching (ACQ) to aggregation-induced emission (AIE) is modulated conveniently by adjusting the charged ratios. The finally obtained AIE polymer is further employed to construct doxorubicin loaded nanoparticles as a promising theranostics platform for cancer therapy.

Preparation, characterization and dyeing wastewater treatment of a new PVDF/PMMA five-bore UF membrane with ß-cyclodextrin and additive combinations.

A new type of polyvinylidene fluoride (PVDF)/polymethyl methacrylate (PMMA) hollow fiber membrane (HFM) with five bores was prepared. The effects of polyvinylpyrrolidone (PVP), ß-cyclodextrine (ß-CD), polyethylene glycol (PEG) and polysorbate 80 (Tween 80) and their combinations on the PVDF/PMMA five-bore HFMs were investigated. The performance and fouling characteristics of five-bore HFMs for dyeing wastewater treatment were evaluated. Results indicated that adding 5 wt.% PVP increased the porosity and water flux of the membrane but decreased the bovine serum albumin (BSA) rejection rate. Adding 5 wt.% ß-CD significantly improved the tensile strength and rejection of the HFMs with no effect on the increase of water flux. The characteristic of the HFMs with different additive combinations proved that the mixture of 5 wt.% PVP and 1 wt.% ß-CD gave the best membrane performance, with a pure water flux of 427.9 L/ m2·h, a contact angle of 25°, and a rejection of BSA of 89.7%. The CODcr and UV254 removal rates of dyeing wastewater treatment were 61.10% and 50.41%, respectively. No breakage or leakage points were found after 120 days of operation, showing their reliable mechanical properties. We set the operating flux to 55 L/m2·h and cross-flow rate to 10%, which can effectively control membrane fouling.

Dynamical Changes of Mandible and Upper Airway After Mandibular Distraction Osteogenesis in Pierre Robin Sequence.

OBJECTIVE: To present the dynamical evaluation of mandible and upper airway size among Chinese infant patients following mandibular distraction osteogenesis in a short-term follow-up and compare predistraction measurements with a normal age- and sex-matched control. METHODS: All the patients have undergone the computed tomography (CT) scan before mandibular distraction osteogenesis (T0), at the end of the distraction phase (T1), and 3 months after the end of the distraction phase before the distractor removal (T2). A CT analyzing computer software MIMICS was utilized to analyze the anatomic variables of upper airway size and mandible size. All analysis was based on a significance level of 0.05. RESULTS: Eight patients with Pierre Robin sequence differed mainly in the mandibular body length and the minimum anteroposterior dimension of the retroglossal airway from the control. After mandibular distraction osteogenesis, the mandibular body length and the ramus height both increased significantly, the ramus height also increased after 3 months of consolidation. Only small increase in the airway dimension of the retroglossal area at T2 was observed compared with T1. CONCLUSION: Mandibular distraction osteogenesis is an effective modality in treating Pierre Robin sequence. Compared with normal control, the main difference may be the length of mandibular body and the area of the retroglossal airway. There may not be an increase in the diameter of airway and the length of mandibular body after 3 months of growth and development in Pierre Robin sequence. Individual surgical plan should be made to gain a better prognosis.

Retention and fatigue performance of modified polyetheretherketone clasps for removable prosthesis.

PURPOSE: Polyetheretherketone (PEEK) is considered as an alternative to metal material for removable partial denture (RPD). However, the retentive force is not strong as a metal RPD. This study investigated the retention and fatigue performance of PEEK clasps with different proportions of clasp arm engaging the undercut to verify a new strategy to improve their clinical performance. METHODS: Three groups (n = 10/group) of PEEK clasps with their terminal 1/3, 2/3 and the whole of retentive arms engaging the undercut were fabricated along with a group (n = 10) of conventional cobalt-chrome (CoCr) clasps as control group. Retentive forces were measured by universal testing machine initially and at an interval of 1500 cycles for a total of 15,000 fatigue cycles. The fatigue cycles were conducted by repeated insertion and removal of the clasp using fatigue testing machine. Each clasp was scanned by Trios3 scanner before and after fatigue test to obtain digital models. The deformation of the clasp was evaluated by root mean square (RMS) through aligning the two models in Geomagic wrap (2021). Scanning electron microscopy (SEM) and finite element analysis were carried out to observe the abrasion and the von Mises stress of the clasp arm. Kruskal-Wallis H test was used to compare the retentive forces and the RMSs of the studied groups followed by Bonferroni multiple comparisons. RESULTS: The whole of PEEK clasp arm engaging the undercut provided higher mean retentive forces (7.99 ± 2.02 N) than other PEEK clasp groups (P < 0.001) and was closer to CoCr clasps (11.88 ± 2.05 N). The RMSs of PEEK clasps were lower than CoCr clasps (P < 0.05) while the differences among PEEK clasps were of no statistical significance (P > 0.05). SEM showed that evidences of surface abrasion were observed on the section that engaged the undercut for all groups of clasps. The stress concentration mainly occurred on the initial part of the retentive arm. The maximum von Mises stress of each group was below the compressive strength of PEEK. CONCLUSIONS: Proportions of PEEK clasp arm engaging the undercut positively influenced the retentive force and the fatigue resistance of PEEK clasps was superior than CoCr clasps. It is a feasible method to improve the retention of PEEK clasps by increasing the proportion of clasp arm engaging the undercut. Clinical trials are needed to further verify this innovation.

A 3D-printed acinar-mimetic silk fibroin-collagen-astragalus polysaccharide scaffold for tissue reconstruction and functional repair of damaged parotid glands.

Salivary glands are the principal organs responsible for secreting saliva in the oral cavity. Tumors, trauma, inflammation, and other factors can cause functional or structural damage to the glands, leading to reduced saliva secretion. In this study, we innovatively prepared a acinar-mimetic silk fibroin-collagen-astragalus polysaccharide (SCA) scaffold using low-temperature three-dimensional (3D) printing and freeze-drying techniques. We evaluated the material properties and cell compatibility of the scaffold in vitro and implanted it into the damaged parotid glands (PG) of rats to assess its efficacy in tissue reconstruction and functional repair. The results demonstrated that the SCA scaffold featured a porous structure resembling natural acini, providing an environment conducive to cell growth and orderly aggregation. It exhibited excellent porosity, water absorption, mechanical properties, and biocompatibility, fulfilling the requirements for tissue engineering scaffolds. In vitro, the scaffold facilitated adhesion, proliferation, orderly polarization, and spherical aggregation of PG cells. In vivo, the SCA scaffold effectively recruited GECs locally, forming gland-like acinar structures that matured gradually, promoting the regeneration of damaged PGs. The SCA scaffold developed in this study supports tissue reconstruction and functional repair of damaged PGs, making it a promising implant material for salivary gland regeneration.

P407 hydrogel loaded with nitric oxide microbubbles promotes angiogenesis and functional improvement in testicular transplantation.

Prepubertal male patients with cancer have decreased fertility after treatment, but there are currently no suitable means for fertility rescue. Testicular transplantation seems to be a promising treatment. The short-term insufficiency of blood supply after transplantation is the key problem that needs to be solved. In this research, nitric oxide (NO), a gas and small molecule transmitter with the effect of promoting angiogenesis, acted at the site of testicular transplantation. Herein, poloxamer-407 (P407) and lipid microbubble materials served as transport carriers for NO and helped NO to function at the transplant site. P407 hydrogel loaded with NO microbubbles (PNO) slowly released NO in vitro. The three-dimensional space of the hydrogel provided a stable environment for NO microbubbles, which is conducive to the continuous release of NO. In this study, 25% PNO (w/v) was selected, and the gelling temperature was 19.47 °C. The gelling efficiency was relatively high at body temperature. Rheological experiments showed that PNO, at this concentration, had stable mechanical properties. The results from in vivo experiments demonstrated that testicular grafts in the PNO group exhibited a notably accelerated blood flow recovery compared to the other groups. Additionally, the PNO group displayed a significant improvement in reproductive function recovery. In conclusion, PNO exhibited slow release of NO, and a small amount of NO promoted angiogenesis in testicular grafts and restored reproductive function.

Polyvinylpyrrolidone Assisted One-Pot Synthesis of Size-Tunable Cocktail Nanodrug for Multifunctional Combat of Cancer.

Background: The in vivo barriers and multidrug resistance (MDR) are well recognized as great challenges for the fulfillment of antitumor effects of current drugs, which calls for the development of novel therapeutic agents and innovative drug delivery strategies. Nanodrug (ND) combining multiple drugs with distinct modes of action holes the potential to circumvent these challenges, while the introduction of photothermal therapy (PTT) can give further significantly enhanced efficacy in cancer therapy. However, facile preparation of ND which contains dual drugs and photothermal capability with effective cancer treatment ability has rarely been reported. Methods: In this study, we selected curcumin (Cur) and doxorubicin (Dox) as two model drugs for the creation of a cocktail ND (Cur-Dox ND). We utilized polyvinylpyrrolidone (PVP) as a stabilizer and regulator to prepare Cur-Dox ND in a straightforward one-pot method. Results: The size of the resulting Cur-Dox ND can be easily adjusted by tuning the charged ratios. It was noted that both loaded drugs in Cur-Dox ND can realize their functions in the same target cell. Especially, the P-glycoprotein inhibition effect of Cur can synergistically cooperate with Dox, leading to enhanced inhibition of 4T1 cancer cells. Furthermore, Cur-Dox ND exhibited pH-responsive dissociation of loaded drugs and a robust photothermal translation capacity to realize multifunctional combat of cancer for photothermal enhanced anticancer performance. We further demonstrated that this effect can also be realized in 3D multicellular model, which possibly attributed to its superior drug penetration as well as photothermal-enhanced cellular uptake and drug release. Conclusion: In summary, Cur-Dox ND might be a promising ND for better cancer therapy.

Preparation of calcium phosphate ion clusters through atomization method for biomimetic mineralization of enamel.

Dental enamel is a mineralized extracellular matrix, and enamel defect is a common oral disease. However, the self-repair capacity of enamel is limited due to the absence of cellular components and organic matter. Efficacy of biomimetic enamel mineralization using calcium phosphate ion clusters (CPICs), is an effective method to compensate for the limited self-healing ability of fully developed enamel. Preparing and stabilizing CPICs presents a significant challenge, as the addition of certain stabilizers can diminish the mechanical properties or biosafety of mineralized enamel. To efficiently and safely repair enamel damage, this study quickly prepared CPICs without stabilizers using the atomization method. The formed CPICs were evenly distributed on the enamel surface, prompting directional growth and transformation of hydroxyapatite (HA) crystals. The study revealed that the mended enamel displayed comparable morphology, chemical composition, hardness, and mechanical properties to those of the original enamel. The approach of repairing dental enamel by utilizing ultrasonic nebulization of CPICs is highly efficient and safe, therefore indicating great promise.

[Treatment of mild hemifacial microsomia in children by autologous nano-fat mixed granule fat transplantation].

Objective: To investigate the effectiveness of autologous nano-fat mixed granule fat transplantation in the treatment of facial soft tissue dysplasia in children with mild hemifacial microsomia (HFM). Methods: A total of 24 children with Pruzansky-Kaban type Ⅰ HFM were admitted between July 2016 and December 2020. Among them, 12 children were treated with autologous nano-fat mixed granule fat (1∶1) transplantation as study group and 12 with autologous granule fat transplantation as control group. There was no significant difference in gender, age, and affected side between groups ( P>0.05). The child's face was divided into region Ⅰ(mental point-mandibular angle-oral angle), region Ⅱ (mandibular angle-earlobe-lateral border of the nasal alar-oral angle), region Ⅲ (earlobe-lateral border of the nasal alar-inner canthus-foot of ear wheel). Based on the preoperative maxillofacial CT scan+three-dimensional reconstruction data, the differences of soft tissue volume between the healthy and affected sides in the 3 regions were calculated by Mimics software to determine the amount of autologous fat extraction or grafting. The distances between mandibular angle and oral angle (mandibular angle-oral angle), between mandibular angle and outer canthus (mandibular angle-outer canthus), and between earlobe and lateral border of the nasal alar (earlobe-lateral border of the nasal alar), and the soft tissue volumes in regions Ⅰ, Ⅱ, and Ⅲ of healthy and affected sides were measured at 1 day before operation and 1 year after operation. The differences between healthy and affected sides of the above indicators were calculated as the evaluation indexes for statistical analysis. At 1 year after operation, the parents, the surgeons, and the nurses in the operation group made a self-assessment of satisfaction according to the frontal photos of the children before and after operation. Results: The study group and the control group were injected with (28.61±8.59) and (29.33±8.08) mL of fat respectively, with no significant difference ( t=0.204, P=0.840). After injection, 1 child in the control group had a little subcutaneous induration, and no related complications occurred in the others. All children in both groups were followed up 1 year to 1 year and 6 months, with an average of 1 year and 4 months in the study group and 1 year and 3 months in the control group. At 1 year after operation, the asymmetry of the healthy and affected sides improved in both groups; the satisfactions of parents, surgeons, and nurses in the study group were all 100% (12/12), while those of the control group were 100% (12/12), 83% (10/12), and 92% (11/12), respectively. The differences between healthy and affected sides in mandibular angle-oral angle, mandibular angle-outer canthus, earlobe-lateral border of the nasal alar, and the soft tissue volume in 3 regions of the two groups after operation were significantly smaller than those before operation ( P<0.05). There was no significant difference in the above indexes between the two groups before operation ( P>0.05). After operation, all indexes were significantly lower in study group than in control group ( P<0.05). Conclusion: Autologous nano-fat mixed granule fat transplantation and autologous granule fat transplantation can both improve the facial soft tissue dysplasia in children with mild HFM, and the former is better than the latter.

Collagen hydrogel with multiple antimicrobial mechanisms as anti-bacterial wound dressing.

Wound infection by multidrug-resistant bacteria seriously threatens human life. Chronic wounds, with necrosis, persistent inflammation, and covered by hypoxic tissue, seriously hinder anti-infection treatments. Herein, we have developed a multifunctional hydrogel dressing with antibacterial activity in the hypoxia environment to promote wound healing. The hydrogel comprises Cypate-conjugated antimicrobial peptides (AMP-Cypates), liposome-encapsulated perfluorodecalin, and recombinant type III collagen. AMP-Cypates exhibited outstanding antibacterial activity, jointly achieved through antimicrobial peptide (AMP) activity, photothermal therapy (PTT), and photodynamic therapy (PDT). The perfluorodecalin liposomes act as the oxygen carrier to mitigate wound hypoxia condition and enhance the efficacy of PDT. The recombinant type III collagen in the hydrogel further promoted the healing of the wounds together with the eradication of bacterial infection. Taken together, the hydrogel dressing provides a platform for integrating multiple antimicrobial mechanisms for the rapid removal of bacterial infection and the healing of chronic wounds.

Dental trauma in endoscopy: A systematic review and experience of a tertiary endoscopy centre.

BACKGROUND: Dental injury is the leading cause of litigation in anaesthesia but an underrecognized preventable complication of endoscopy. AIM: To determine frequency and effects of dental injury in endoscopy, we present findings from an audit of outpatient endoscopy procedures conducted at a tertiary university hospital and a systematic review of literature. METHODS: Retrospective review of 11265 outpatient upper endoscopy procedures over the period of 1 June 2019 to 31 May 2021 identified dental related complications in 0.284% of procedures. Review of literature identified a similar rate of 0.33%. RESULTS: Pre-existing dental pathology or the presence of prostheses makes damage more likely but sound teeth may be affected. Pre-endoscopic history and tooth examination are key for risk stratification and may be conducted succinctly with limited time outlay. Tooth retrieval should be prioritized in the event of dental injury to minimize aspiration and be followed by prompt dental consultation for specific management. CONCLUSION: Dental complications occur in approximately 1 in 300 of upper endoscopy cases. These are easily preventable by pre-endoscopy screening. Protocols to mitigate dental injury are also suggested.

Antimicrobial Peptide-Loaded Gelatinase-Responsive Photothermal Nanogel for the Treatment of Staphylococcus aureus-Infected Wounds.

As the most common pathogen of community and nosocomial infection, the resistance of Staphylococcus aureus (S. aureus) to traditional antibiotics is still increasing with years. Although the potent antibacterial activity of antimicrobial peptides (AMPs) has been widely confirmed, the unpredictable cytotoxicity remains the biggest obstacle to their clinical application. The development of a targeted drug delivery system for S. aureus is a practical strategy to ameliorate the inherent limitations of AMPs. In this work, we constructed an AMP release nanogel (cypate-GNPs@Cy3-AMP, CGCA) of S. aureus infection microenvironment using gelatinase nanoparticles (GNPs) for toxicity control and bacterial clearance. Gelatinase present in the infected site degrades GNPs, thus releasing Cy3-AMP in situ to destroy bacterial cells. Cypate modified on the surface of GNPs supports CGCA to generate localized heat under near-infrared (NIR) laser irradiation, which together with AMPs could cause irreversible physical damage to bacteria. In addition, the encapsulation from GNPs not only effectively limited the toxicity of AMPs but also significantly promoted cell proliferation and migration in vitro. In the mouse infection model, CGCA also exhibited excellent effects of bacterial clearance and wound healing, providing a potential direction for the correct use of AMPs.

Silk Fibroin/Collagen/Hydroxyapatite Scaffolds Obtained by 3D Printing Technology and Loaded with Recombinant Human Erythropoietin in the Reconstruction of Alveolar Bone Defects.

The fast osteogenesis of the large alveolar fossa and the maintenance of the height of the alveolar ridge after tooth extraction have always been a clinical challenge. Therefore, this work describes the creation of innovative silk fibroin/collagen/hydroxyapatite (SCH) biological scaffolds by 3D printing technology, which are loaded with recombinant human erythropoietin (rh-EPO) for the reconstruction of bone defects. Low-temperature 3D printing can maintain the biological activity of silk fibroin and collagen. The SCH scaffolds showed the ideal water absorption and porosity, being a sustained-release carrier of rh-EPO. The optimized scaffolds had ideal mechanical properties in vitro, and MC3T3-E1 cells could easily adhere and proliferate on it. In vivo experiments in rabbits demonstrated that the composite scaffolds gradually degraded and promoted the accumulation and proliferation of osteoblasts and the formation of collagen fibers, significantly promoting the reconstruction of mandibular defects. In this study, a novel composite biological scaffold was prepared using 3D printing technology, and the scaffold was innovatively combined with the multifunctional growth factor rh-EPO. This provides a new optimized composite material for the reconstruction of irregular mandible defects, and this biomaterial is promising for clinical reconstruction of alveolar bone defects.

Liposome Loaded Ion/Temperature Dual Responsive Gellan Gum Hydrogel as Potential Nasal-To-Brain Delivery System.

Intranasal administration, which can bypass the blood-brain barrier (BBB), is widely recognized as a promising strategy for high-efficiency drug delivery to the brain. Herein, for the purpose of effectively delivering drugs to the brain via intranasal administration, glutathione (GSH)-modified gellan gum (GSH-GG) with ion/temperature dual responsive properties was synthesized and encapsulated on galanthamine hydrobromide (GH)-loaded liposomes (GH-Lipo) for effective GH delivery to the brain (GH-Lipo@GSH-GG). Our results demonstrated that GSH-GG greatly decreased the gelation temperature of GG from 44.0 °C to 22.1 °C without compromising its ion responsiveness. Moreover, GSH-GG had a good protection ability for GH-loaded liposomes without affecting its drug release. Most importantly, the finally obtained GH-Lipo@GSHGG showed acceptable targeted delivery of GH to the brain upon in vivo administration. Therefore, this formulation can be employed as a potential delivery system in nasal-to-brain delivery.

Small Molecule Modifications Significantly Increase the Transfection Efficiency of Low-Molecular Polymer.

Gene vectors with high biocompatibility and transfection efficiency are critical for successful gene therapy. PEI 25K (Polyethyleneimine 25K) is a common polymeric gene vector that has been employed as a positive control material in gene transfection studies due to its good performance in endosome escape. PEI 25K's indegradability and abundance of positive charges, on the other hand, cause toxicity in cells, limiting its use. In this study, we developed the PEI-ER non-viral vector by adding an endoplasmic reticulum (ER) targeting ligand to low molecular weight PEI 1.8K. These small molecule modifications dramatically improved PEI transfection efficiency while barely interfering with compatibility. PEI-ER/DNA complexes were discovered to enter the cell via caveolin-mediated endocytosis, avoiding destruction in the endosome. We believe that this little chemical alteration is a simple solution to enhance the efficacy of cationic polymer vectors in gene transport, and it has a lot of medicinal applications.

Bifunctional Smart Hydrogel Dressing with Strain Sensitivity and NIR-Responsive Performance.

Smart response hydrogel has a broad application prospect in human health real-time monitoring due to its responses to a variety of stimuli. In this study, we developed a novel smart hydrogel dressing based on conductive MXene nanosheets and a temperature-sensitive PNIPAm polymer. γ-Methacryloxypropyltrimethoxysilane (KH570) was selected to functionalize the surface of MXene further to improve the interface compatibility between MXene and PNIPAm. Our prepared K-M/PNIPAm hydrogel was found to have a strain-sensitive property, as well as a respond to NIR phase change and volume change. When applied as a strain flexible sensor, this K-M/PNIPAm hydrogel exhibited a high strain sensitivity with a gauge factor (GF) of 4.491, a broad working strain range of ≈250%, a fast response of ∼160 ms, and good cycle stability (i.e., 3000 s at 20% strain). Besides, this K-M/PNIPAm hydrogel can be used as an efficient NIR light-controlled drug release carrier to achieve on-demand drug release. This work paved the way for the application of smart response hydrogel in human health real-time monitoring and NIR-controlled drug release functions.

Silica-Coated Fe3O4 Nanoparticles as a Bifunctional Agent for Magnetic Resonance Imaging and ZnII Fluorescent Sensing.

Bifunctional magnetic/fluorescent core-shell silica nanospheres (MNPs) encapsulated with the magnetic Fe3O4 core and a derivate of 8-amimoquinoline (N-(quinolin-8-yl)-2-(3-(triethoxysilyl) propylamino) acetamide) (QTEPA) into the shell were synthesized. These functional MNPs were prepared with a modified stöber method and the formed Fe3O4@SiO2-QTEPA core-shell nanocomposites are biocompatible, water-dispersible, and stable. These prepared nanoparticles were characterized by X-ray power diffraction (XRD), transmission electron microscopy (TEM), thermoelectric plasma Quad II inductively coupled plasma mass spectrometry (ICP-MS), superconducting quantum interference device (SQUID), TG/DTA thermal analyzer (TGA) and Fourier transform infrared spectroscopy (FTIR). Further application of the nanoparticles in detecting Zn2+ was confirmed by the fluorescence experiment: the nanosensor shows high selectivity and sensitivity to Zn2+ with a 22-fold fluorescence emission enhancement in the presence of 10 µM Zn2+. Moreover, the transverse relaxivity measurements show that the core-shell MNPs have T2 relaxivity (r2) of 155.05 mM-1 S-1 based on Fe concentration on the 3.0 T scanner, suggesting that the compound can be used as a negative contrast agent for MRI. Further in vivo experiments showed that these MNPs could be used as MRI contrast agent. Therefore, the new nanosensor provides the dual modality of magnetic resonance imaging and optical imaging.