TRIM52 knockdown inhibits proliferation, inflammatory responses and oxidative stress in IL-1ß-induced synovial fibroblasts to alleviate temporomandibular joint osteoarthritis.

To explore the mechanism of tripartite motif 52 (TRIM52) in the progression of temporomandibular joint osteoarthritis (TMJOA). Gene and protein expression were tested by quantitative real-time polymerase chain reaction and western blot, respectively. The levels of pro-inflammatory cytokines and oxidative stress factors were evaluated using enzyme-linked immunosorbent assay and biochemical kit, respectively. Cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays were carried out to assess cell proliferation. Immunofluorescence was used to detect the expression of CD68 and Vimentin in primary synovial fibroblasts (SFs). Haematoxylin and eosin staining and Safranin O/Fast green were used to evaluate the pathological damage of synovial and cartilage tissue in rats. TRIM52 was upregulated in the synovial tissue and SFs in patients with TMJOA. Interleukin (IL)-1ß treatment upregulated TRIM52 expression in TMJOA SFs and normal SF (NSF), promoting cell proliferation, inflammatory response and oxidative stress in NSF, SFs. Silence of TRIM52 relieved the cell proliferation, inflammatory response and oxidative stress induced by IL-1ß in SFs, while overexpression of TRIM52 enhanced IL-1ß induction. Meanwhile, IL-1ß induction activated toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB pathway, which was augmented by upregulation of TRIM52 in NSF, and was attenuated by TRIM52 knockdown in SFs. Besides, pyrrolidinedithiocarbamic acid ameliorated IL-1ß-induced proliferation and inflammatory response by inhibiting TLR4/NF-κB signalling. Meanwhile, TRIM52 knockdown inhibited cell proliferation, oxidative stress and inflammatory response in IL-1ß-induced SFs through downregulation of TLR4. TRIM52 promoted cell proliferation, inflammatory response, and oxidative stress in IL-1ß-induced SFs. The above functions were mediated by the activation of TLR4/NF- κB signal pathway.

Overcoming the Low-Stability Bottleneck in the Clinical Translation of Liposomal Pressurized Metered-Dose Inhalers: A Shell Stabilization Strategy Inspired by Biomineralization.

Currently, several types of inhalable liposomes have been developed. Among them, liposomal pressurized metered-dose inhalers (pMDIs) have gained much attention due to their cost-effectiveness, patient compliance, and accurate dosages. However, the clinical application of liposomal pMDIs has been hindered by the low stability, i.e., the tendency of the aggregation of the liposome lipid bilayer in hydrophobic propellant medium and brittleness under high mechanical forces. Biomineralization is an evolutionary mechanism that organisms use to resist harsh external environments in nature, providing mechanical support and protection effects. Inspired by such a concept, this paper proposes a shell stabilization strategy (SSS) to solve the problem of the low stability of liposomal pMDIs. Depending on the shell material used, the SSS can be classified into biomineralization (biomineralized using calcium, silicon, manganese, titanium, gadolinium, etc.) biomineralization-like (composite with protein), and layer-by-layer (LbL) assembly (multiple shells structured with diverse materials). This work evaluated the potential of this strategy by reviewing studies on the formation of shells deposited on liposomes or similar structures. It also covered useful synthesis strategies and active molecules/functional groups for modification. We aimed to put forward new insights to promote the stability of liposomal pMDIs and shed some light on the clinical translation of relevant products.

Dual peptides-modified cationic liposomes for enhanced Lung cancer gene therapy by a gap junction regulating strategy.

BACKGROUND: Gene therapy for lung cancer has emerged as a novel tumor-combating strategy for its superior tumor specificity, low systematical toxicity and huge clinical translation potential. Especially, the applications of microRNA shed led on effective tumor ablation by directly interfering with the crucial gene expression, making it one of the most promising gene therapy agents. However, for lung cancer therapy, the microRNA treatment confronted three bottlenecks, the poor tumor tissue penetration effect, the insufficient lung drug accumulation and unsatisfied gene transfection efficiency. To address these issues, an inhalable RGD-TAT dual peptides-modified cationic liposomes loaded with microRNA miR-34a and gap junction (GJ) regulation agent all-trans retinoic acid (ATRA) was proposed, which was further engineered into dry powder inhalers (DPIs). RESULTS: Equipped with a rough particle surface and appropriate aerodynamic size, the proposed RGD-TAT-CLPs/ARTA@miR-34a DPIs were expected to deposit into the deep lung and reach lung tumor lesions guided by targeting peptide RGD. Assisted by cellular transmembrane peptides TAT, the RGD-TAT-CLPs/ARTA@miR-34a was proven to be effectively internalized by cancer cells, enhancing gene transfection efficiency. Then, the GJ between tumor cells was upregulated by ARTA, facilitating the intercellular transport of miR-34a and boosting the gene expression in the deep tumor. CONCLUSION: Overall, the proposed RGD-TAT-CLPs/ARTA@miR-34a DPIs could enhance tumor tissue penetration, elevate lung drug accumulation and boost gene transfection efficiency, breaking the three bottlenecks to enhancing tumor elimination in vitro and in vivo. We believe that the proposed RGD-TAT-CLPs/ARTA@miR-34a DPIs could serve as a promising pulmonary gene delivery platform for multiple lung local disease treatments.

Knowledge, attitudes, and practice of non-medical students regarding impacted teeth: a cross-sectional study.

OBJECTIVES: To explore the knowledge, attitudes, and practice (KAP) of non-medical students regarding impacted teeth and the factors associated with KAP. MATERIALS AND METHODS: This cross-sectional study enrolled non-medical students at two universities (Northeastern University and Shenyang Conservatory of Music) in northeastern China between December 2022 and February 2023. Scores > 70% were defined as adequate knowledge, positive attitudes, and proactive practice. RESULTS: A total of 519 non-medical students participated in this study. Most participants were male (54.72%), ≤ 20 years of age (72.83%), and freshmen (36.03%). The mean knowledge score was 4.98 ± 3.46 (possible range: 0-10), indicating poor knowledge (49.80%). The multivariable analysis showed that having impacted teeth were independently associated with adequate knowledge (OR = 3.114, 95% CI: 1.589-6.103, P = 0.001). The mean attitude score was 24.65 ± 3.78 (possible range: 7-35), indicating favorable attitudes (70.43%). The knowledge (OR = 1.182, 95% CI: 1.116-1.251, P < 0.001), junior grade (OR = 0.541, 95% CI: 0.327-0.895, P = 0.017), senior grade and above (OR = 0.477, 95% CI: 0.274-0.829, P = 0.009), and a history of impacted tooth extraction (OR = 2.386, 95% CI: 1.048-5.436, P = 0.038) were independently associated with the good attitudes. The mean practice score was 21.45 ± 5.64 (possible range: 6-30), indicating positive practice (71.50%). The knowledge (OR = 1.074, 95% CI: 1.017-1.133, P = 0.010) and female (OR = 1.501, 95% CI: 1.052-2.141, P = 0.025) were independently associated with the proactive practices. CONCLUSIONS: Non-medical students had poor knowledge but favorable attitudes and good practice toward impacted teeth. Non-medical students require additional education and awareness about the importance of early detection and management of impacted teeth. CLINICAL RELEVANCE: The study highlights the need for improved education and awareness among non-medical students regarding impacted teeth.

Factors affecting nasal drug delivery and design strategies for intranasal drug delivery. / é¼»è ”è¯ç‰©é€’é€çš„å½±å“å› ç´ å’Œæé«˜é€’é€æ•ˆçŽ‡çš„è®¾è®¡ç­–ç•¥.

Intranasal drug delivery system is a non-invasive drug delivery route with the advantages of no first-pass effect, rapid effect and brain targeting. It is a feasible alternative to drug delivery via injection, and a potential drug delivery route for the central nervous system. However, the nasal physiological environment is complex, and the nasal delivery system requires "integration of medicine and device". Its delivery efficiency is affected by many factors such as the features and formulations of drug, delivery devices and nasal cavity physiology. Some strategies have been designed to improve the solubility, stability, membrane permeability and nasal retention time of drugs. These include the use of prodrugs, adding enzyme inhibitors and absorption enhancers to preparations, and new drug carriers, which can eventually improve the efficiency of intranasal drug delivery. This article reviews recent publications and describes the above mentioned aspects and design strategies for nasal intranasal drug delivery systems to provide insights for the development of intranasal drug delivery systems.

Is insufficient sleep duration a risk indicator for periodontal disease? A systematic review.

OBJECTIVES: In this study, we conducted a systematic review and meta-analysis to assess whether people who achieved <7 h of sleep were more likely to develop periodontal disease (PD). SOURCES: We executed electronic searches in the PubMed, EMBASE and Cochrane Library, as well as a manual search of articles published by leading journals in related fields, for observational studies, published in English from 1 January 1966 to 31 March 2021.which evaluated the relationship between sleep duration and PD. The Agency for Healthcare Research and Quality (AHRQ) quality evaluation scale was used for the cross-sectional studies, and the random effects model was used to summarize the effect sizes in the included studies with a 95% confidence interval (CI). RESULTS: A total of six cross-sectional studies met the inclusion criteria, totaling 107,777 participants, of which 69,773 had PD. The results of the present indicated that shorter sleep duration (<7 h) is significantly associated with PD (Odd ratio [OR], 1.19; 95% CI, 1.16-1.23; p < 0.001; I2 , 0.0%, I2 interval, 0%-75%). The strength of the sensitivity analysis and cumulative meta-analysis confirmed the reliability of the results. CONCLUSION: Although the inclusion of only six studies makes it difficult to explore whether there is a publication bias, we found that insufficient sleep duration was closely related to PD, and we therefore speculated that getting enough sleep may help prevent PD.

Three Different Interaction Patterns between MCM-41 and Proteins.

As one of the most studied mesoporous silica nanoparticles (MSNs) in drug delivery systems, Mobil Composition of Matter No. 41 (MCM-41) possesses unique properties including perfect channel architecture, excellent load capacity, and good biocompatibility. However, the applications of MCM-41 nanoparticles in drug delivery have not yet been industrialized, due to the interaction between MCM-41 and biomolecules (especially proteins) that affect their in vivo behaviors after dosing. To investigate the interactions between MCM-41 and proteins, this study selected bovine serum albumin (BSA), lysozyme (Lyso), and bovine hemoglobin (BHb) as model proteins and characterized the ultraviolet-visible, fluorescence, circular dichroism spectra and the protein adsorption of MCM-41-protein complex. The UV-Vis spectra exhibited the different absorption increment degrees of three proteins. The fluorescence spectra showed that the fluorescence intensity of proteins changed by different trends. The CD spectra indicated that the secondary structure changes were ranked as BSA > Lyso > BHb, which is consistent with the protein's adsorption capability on MCM-41. It was shown that there were three different patterns of MCM-41-proteins interactions. The hydrophilic and low-charged BSA followed the strong interaction pattern, the hydrophilic but heavily charged Lyso followed the moderate interaction pattern, and the hydrophobic BHb followed the weak interaction pattern. Different interaction patterns would lead to different effects on the structural properties of proteins, the surface chemistry of MCM-41, and the absorption capability of proteins on MCM-41. We believe our study will provide a better insight into the application of MCM-41 nanoparticles in drug delivery systems.

Dry Suspension Containing Coated Pellets with pH-Dependent Drug Release Behavior for the Taste-masking of Azithromycin.

Azithromycin (AZI) is a commonly used antibiotic with extremely bitter taste that severely decreases the compliance of patients. Besides, the poor solubility of AZI in alkaline pH makes it difficult to be absorbed in the small intestine. To achieve the dual effects of taste masking and enhanced absorption, AZI-loaded pellets were coated by polymer blend of Eudragit®RL30D and Eudragit®L30D-55. The coated pellets could avoid drug release in the oral environment (pH 5-7) but release rapidly in the gastric environment (pH 1-3). Then, the coated pellets were further formulated into dry suspension to address the problem of dysphagia. The taste-masking effect tests by electronic tongue and human volunteers revealed that the dry suspension was more effective to improve the bitter taste of AZI than the commercial product. Therefore, this study provided an economical and feasible approach for taste masking with good practical application prospect.

Improving Water-Absorption and Mechanical Strength: Lyotropic Liquid Crystalline-Based Spray Dressings as a Candidate Wound Management System.

A spray dressing based on lyotropic liquid crystalline (LLC) with adjustable crystalline lattices was investigated in this study. It possesses water-triggering phase transition property and ease of spraying on wound, as well as stable drug encapsulation and controllable drug release. When it comes to wound with exudate, adequate water absorption and sustainable mechanical strength after water absorption was important for a good dressing, while most of the normal LLC dressings were still unable to meet such standards. Herein, a type of hyaluronic acid (HA)-incorporated LLC-based spray dressing (HLCSD) was developed to overcome the above limitations. After comparing HAs with different molecular weights (MWs) and concentrations, 3% HA with MW of 800~1000 kD was chosen as an ideal amount of excipients to add into the HLCSD. The water absorption of HLCSD precursor increased by 150% with the appearance of enlarged water channels. The complex modulus of HLCSD gel also increased from 1 to 100 kPa, which suggested lasting wound coverage and good patient compliance when used clinically. The spraying and phase transition properties of HLCSD was studied and showed acceptable changes. Moreover, good safety comparable with the commercial product Purilon® was also demonstrated in an in vivo acute skin irritation test. Thus, the improved HLCSD was a promising dressing for exudation wound treatment.

Brain Lipid Dynamics in Amyloid Precursor Protein/Presenilin 1 Mouse Model of Early Alzheimer's Disease by Desorption Electrospray Ionization and Matrix Assisted Laser Desorption Ionization-Mass Spectrometry Imaging Techniques.

Alzheimer's disease (AD) is closely associated with lipid metabolism dysfunction. However, space distribution and metabolism of aberrant lipids in the brain of early-stage AD mouse remain unclear. In our current work, a novel lipidomics method based on mass spectrometry imaging was developed to visually disclose molecular perturbation and characterize space distribution in the brain of double transgenic amyloid precursor protein/presenilin 1 mouse (2 and 3 months old). Significant changes were detected, including phosphatidylethanolamines, phosphatidylcholines, fatty acids, lysophospholipids, and glycerides in AD mouse brain. The results in this study suggest that these significantly altered lipid metabolic pathways (glycerophospholipid metabolism) may be implicated in early-stage AD. Our work deepens the understanding of the physio-pathologic mechanism of early-stage AD.

Versatile Nanoscale Metal-Organic Frameworks (nMOFs): An Emerging 3D Nanoplatform for Drug Delivery and Therapeutic Applications.

For decades, nanoscale metal-organic frameworks (nMOFs) have attracted extensive interest in biomedicine due to their distinct characteristics, including facile synthesis, porous interior, and tunable biocompatibility. With high porosity, versatile nMOFs allow for the facile encapsulation of various therapeutic agents with exceptionally high payloads. Constructed from metal ions and organic linkers through coordination bonds, nMOFs with plentiful functional groups enable the surface modification for active targeting and enhanced biocompatibility. This review outlines the up-to-date progresses on the exploration of nMOFs in the field of biomedicine. First, the classification and synthesis of nMOFs are discussed, followed by the concrete introduction of drug loading strategies of nMOFs and mechanisms of stimulation-responsive drug release. Second, the smart designs of the nMOFs-based platforms for anticancer and antibacterial treatment are summarized. Finally, the basic challenges faced by nMOFs research and the great potential of biomimetic nMOFs are presented. This review article affords an inspiring insight into the interdisciplinary research of nMOFs and their biomedical applications, which holds great expectation for their further clinical translation.

Comparison of Autologous Platelet-Rich Plasma and Chitosan in the Treatment of Temporomandibular Joint Osteoarthritis: A Retrospective Cohort Study.

PURPOSE: The purpose of this article is to study the effect of autologous platelet-rich plasma (PRP) injected into the upper cavity of the temporomandibular joint (TMJ) on the treatment of TMJ osteoarthritis. PATIENTS AND METHODS: We retrospectively analyzed the data of 27 patients with TMJ osteoarthritis treated at the China Medical University Hospital of Stomatology from September 2018 to September 2019. Maximal interincisal opening, pain intensity, and TMJ sounds were recorded and compared before treatment and at the 3rd and 6th months after the treatment. SPSS 24.0 software was used to analyze the data of each group, and the imaging changes in the condylar bone were compared before and 6 months after the treatment. The P-value was set at .05. RESULTS: Better results were observed in the group treated with PRP on maximal interincisal opening and pain intensity than in the group receiving chitosan treatment. Regarding TMJ sounds, relief was observed in both groups, with no significant difference. CONCLUSIONS: The effect of PRP on the improvement of the maximal interincisal opening and pain intensity of patients with TMJ osteoarthritis is better than that of chitosan. However, it should be noted that the incidence of complications associated with the injection of PRP may be higher than that with injection of chitosan.

Major difference in particle size, minor difference in release profile: a case study of solid lipid nanoparticles.

Solid lipid nanoparticles (SLN) have been widely used in a variety of drug delivery routes, which have the outstanding advantage of controlled drug release. The release of SLN is dominated by many factors, among which the particle size of SLN is a critical one. The aim of this project was to explore the relationship between drug release profile and particle size of SLN. SLN were synthesized via the hot high-pressure homogenization (HPH) method, budesonide (BUD) was used as the model drug, and BUD-SLN1-BUD-SLN4 with increasing particle size was obtained, i.e. 120, 240, 360, and 480 nm. The prepared SLN has good encapsulation efficiency, drug loading capacity, and stability. In vitro release behavior studies showed that the cumulative release of BUD-SLN in Tris-Maleate (Tris-M) media was negligible, while that in Tris-M plus pancreatin media or Tris-M-ethanol media obeyed Ritger-Peppas model or first-order kinetic model, respectively. Noticeably, the release behavior of SLN was to some extent related to the average particle size of SLN, but the correlation was insignificant when the intersection degree of particle size distribution was great. This study provides a new idea for the understanding of in vitro release of SLN and has a certain referencing value for the research and development of novel nanomedicines.

Stability Evaluation of Lyotropic Liquid Crystalline Precursor for the Co-delivery of Chlorhexidine and Silver Nanoparticles.

Sealing the therapeutic agents in the root canal is considered to be an essential step in root canal therapy. The lyotropic liquid crystalline precursor (LLCP) incorporated with chlorhexidine (CHX) and silver nanoparticles (Ag-NPs) has been confirmed as a promising candidate for root canal therapy in the previous study. Importantly, the stability of the LLCP system was a significant determinant for its therapeutic effect and further application. The objective of this study was to comprehensively investigate the stability of the LLCP incorporated with CHX and Ag-NPs. The oil-water partition coefficient of CHX and Ag-NPs was measured. The water absorption and the physical stability of drug-loaded LLCP solution were studied. Stability under high temperature, high humidity, and strong light irradiation was also investigated. The results demonstrated that CHX and Ag-NPs could be entrapped in the water channel of LLCP, indicating the low tendency of drugs leakage. The drug-loaded LLCP was a pseudoplastic fluid and it showed an excellent physical stability with a sedimentation rate of 0.981 and a settling time of 26~28 h. The payload of LLCP was confirmed to weaken the water absorption behavior, which facilitated its transformation to cubic liquid crystal. The stress testing under high temperature, high humidity, and strong light irradiation also manifested that the LLCP was stable when stored under moisture-proof condition. In conclusion, the developed LLCP incorporated with CHX and Ag-NPs was highly stable during storage and qualified for further application.

Inhalable Nanocomposite Microparticles with Enhanced Dissolution and Superior Aerosol Performance.

Previous studies have shown that combining colistin (Col), a cationic polypeptide antibiotic, with ivacaftor (Iva), a cystic fibrosis (CF) drug, could achieve synergistic antibacterial effects against Pseudomonas aeruginosa. The purpose of this study was to develop dry powder inhaler formulations for co-delivery of Col and Iva, aiming to treat CF and lung infection simultaneously. In order to improve solubility and dissolution for the water-insoluble Iva, Iva was encapsulated into bovine serum albumin (BSA) nanoparticles (Iva-BSA-NPs). Inhalable composite microparticles of Iva-BSA-NPs were produced by spray-freeze-drying using water-soluble Col as the matrix material and l-leucine as an aerosol enhancer. The optimal formulation showed an irregularly shaped morphology with fine particle fraction (FPF) values of 73.8 ± 5.2% for Col and 80.9 ± 4.1% for Iva. Correlations between "D×ρtapped" and FPF were established for both Iva and Col. The amorphous solubility of Iva is 66 times higher than the crystalline solubility in the buffer. Iva-BSA-NPs were amorphous and remained in the amorphous state after spray-freeze-drying, as examined by powder X-ray diffraction. In vitro dissolution profiles of the selected DPI formulation indicated that Col and Iva were almost completely released within 3 h, which was substantially faster regarding Iva release than the jet-milled physical mixture of the two drugs. In summary, this study developed a novel inhalable nanocomposite microparticle using a synergistic water-soluble drug as the matrix material, which achieved reduced use of excipients for high-dose medications, improved dissolution rate for the water-insoluble drug, and superior aerosol performance.

Sialendoscopy-Assisted Treatment of Stensen's Duct Injury: A Case Series.

PURPOSE: To evaluate the clinical value of sialendoscopy in the treatment of Stensen's duct injury. PATIENTS AND METHODS: A total of 5 patients with Stensen's duct injuries who had been treated from December 2017 to April 2019 were included in the present study. The operations were performed with the help of a sialendoscope. All patients were followed for 6 months. RESULTS: The distal end of the ductal system was found precisely with the use of the sialendoscope, and the proximal end was identified by the location of the distal end. The end-to-end anastomosis was performed successfully. None of the patients complained of salivary gland fistula at the 6-month follow-up examination. CONCLUSIONS: The stumps of the ductal system could be precisely and effectively located with the help of a sialendoscope.

Calcitriol tablets with hybrid lipid-based solid dispersions with enhanced stability and content uniformity.

Calcitriol, as the biologically active form of vitamin D3, is essential for patients with renal osteopathy. The solubilization, stabilization, and content uniformity are key issues in its formulation development. In our previous study, the incomplete release of calcitriol was solved by using the hybrid lipid-based solid dispersion (SD) for calcitriol. However, good stability and content uniformity are still urgently needed. In this study, solid lipid with antioxidant properties and liquid lipid compatible with calcitriol were employed as hybrid lipid carrier (HLC) to establish a solid dispersion. Moreover, the content uniformity of tablets with hybrid lipid carrier based SDs (HLCTs) was further guaranteed due to the multi-dispersion of calcitriol in HLC, solidification, and blank granules. Additionally, the compression of the blank granules was adjusted by the water content. The mixing method of calcitriol-containing and blank granules was also optimized. The obtained HLCTs were evaluated for hardness, disintegration time, in vitro drug dissolution, content uniformity, and stability. Satisfactory HLCTs were developed successfully in this study with superior content uniformity and better stability than the commercial soft capsule (Rocaltrol®). It was proved to be a promising formulation for drugs with poor water-solubility, instability to oxygen and heat, and dose-related toxicity.

Development of Aggregation-Caused Quenching Probe-Loaded Pressurized Metered-Dose Inhalers with Fluorescence Tracking Potentials.

Recently, pressurized metered-dose inhalers (pMDIs) are getting more attention as an effective approach of pulmonary drug delivery, and nanoparticle-based formulations have become a new generation of pMDIs, especially for water insoluble drugs. Up until now, there is no clinical application of nanoparticle-based pMDIs. The main hurdle remains in the lack of knowledge of the in vivo fate of those systems. In this study, a fluorescent probe named P4 with aggregation-caused quenching (ACQ) effect was loaded in the nanoparticle-based pMDIs to track the in vivo fate. P4 probe expressed strong fluorescence when distributed in intact nanoparticles, but quenched in the in vivo aqueous environment due to molecular aggregation. Experimentally, P4 probe was encapsulated into solid lipid nanoparticles (SLN) as P4-SLN, and then, the formulation of pMDIs was optimized. The content (w/w) of the optimal formulation (P4-SLN-pMDIs) was as follows: 6.02% Pluronic® L64, 12.03% ethanol, 0.46% P4-SLN, and 81.49% 1,1,1,2-tetrafluoroethane (HFA-134a). P4-SLN-pMDI was transparent in appearance, possessed a particle size of 132.07 ± 3.56 nm, and the fine particle fraction (FPF) was 39.53 ± 1.94%, as well good stability was shown within 10 days. The results indicated P4-SLN-pMDI was successfully prepared. Moreover, the ACQ property of P4-SLN-pMDIs was verified, which ensured the fluorescence property as a credible tool for in vivo fate study. Taken together, this work established a platform that could provide a firm theoretical support for exploration of the in vivo fate of nanoparticle-based pMDIs in subsequent studies. Grapical abstract.

The practical self-targeted oncolytic adenoviral nanosphere based on immuno-obstruction method via polyprotein surface precipitation technique enhances transfection efficiency for virotherapy.

Recent developments in tumour treatment had focused on virotherapies that were currently revolutionising new innovated treatment pathways. This study focused on the fabrication of oncolytic adenoviral vector (Ad) nanosphere that self-targeted at lung tumour cells (A549), utilising the immune response for upper respiratory tract infection, caused by the Ad infection. This system was dependent upon T-cell immune response, surface charge and blood metabolism. Oncolytic Ad attacked lung A549 tumour cells by incorporated its own DNA to replace A549's, the triggered immune response generated T-cells also further attack A549. Direct Ad injection was demonstrated to be lethal and prohibited in vivo. In this research a multifunctional principal using polyprotein surface precipitation technique (PSP) whist maintaining biological controls for self-assembly polyprotein Ad nanosphere both biocompatible and reproducible, was demonstrated as a result of the enhanced transfection efficiency and a successful multifunctional drug delivery system for virotherapy.

Cationic Polymer-Mediated CRISPR/Cas9 Plasmid Delivery for Genome Editing.

Delivery of CRISPR (clustered regularly interspaced short palindromic repeats)/CRISPR-associated protein-9 (Cas9) represents a major hurdle for successful clinical translation of genome editing tools. Owing to the large size of plasmids that encode Cas9 and single-guide RNA (sgRNA), genome editing efficiency mediated by current delivery carriers is still unsatisfactory to meet the requirement for its real applications. Herein, cationic polymer polyethyleneimine-ß-cyclodextrin (PC), known to be efficient for small plasmid transfection, is reported to likewise mediate efficient delivery of plasmid encoding Cas9 and sgRNA. Whereas PC can condense and encapsulate large plasmids at high N/P ratio, the delivery of plasmid results in efficient editing at two genome loci, namely, hemoglobin subunit beta (19.1%) and rhomboid 5 homolog 1 (RHBDF1) (7.0%). Sanger sequencing further confirms the successful genome editing at these loci. This study defines a new strategy for the delivery of the large plasmid encoding Cas9/sgRNA for efficient genome editing.