Replenishment of mitochondrial Na+ and H+ by ionophores potentiates cutaneous wound healing in diabetes.

Diabetic foot ulcer (DFU) is a highly morbid complication in patients with diabetes mellitus, necessitating the development of innovative pharmaceuticals to address unmet medical needs. Sodium ion (Na+) is a well-established mediator for membrane potential and osmotic equilibrium. Recently, Na+ transporters have been identified as a functional regulator of regeneration. However, the role of Na+ in the intricate healing process of mammalian wounds remains elusive. Here, we found that the skin wounds in hyponatremic mice display a hard-to-heal phenotype. Na+ ionophores that were employed to increase intracellular Na+ content could facilitate keratinocyte proliferation and migration, and promote angiogenesis, exhibiting diverse biological activities. Among of them, monensin A emerges as a promising agent for accelerating the healing dynamics of skin wounds in diabetes. Mechanistically, the elevated mitochondrial Na+ decelerates inner mitochondrial membrane fluidity, instigating the production of reactive oxygen species (ROS), which is identified as a critical effector on the monensin A-induced improvement of wound healing. Concurrently, Na+ ionophores replenish H+ to the mitochondrial matrix, causing an enhancement of mitochondrial energy metabolism to support productive wound healing programs. Our study unfolds a new role of Na+, which is a pivotal determinant in wound healing. Furthermore, it directs a roadmap for developing Na+ ionophores as innovative pharmaceuticals for treating chronic dermal wounds in diabetic patients.

SARS-CoV-2 bivalent mRNA vaccine with broad protection against variants of concern.

Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has rapidly spread around the globe. With a substantial number of mutations in its Spike protein, the SARS-CoV-2 Omicron variant is prone to immune evasion and led to the reduced efficacy of approved vaccines. Thus, emerging variants have brought new challenges to the prevention of COVID-19 and updated vaccines are urgently needed to provide better protection against the Omicron variant or other highly mutated variants. Materials and methods: Here, we developed a novel bivalent mRNA vaccine, RBMRNA-405, comprising a 1:1 mix of mRNAs encoding both Delta-derived and Omicron-derived Spike proteins. We evaluated the immunogenicity of RBMRNA-405 in BALB/c mice and compared the antibody response and prophylactic efficacy induced by monovalent Delta or Omicron-specific vaccine with the bivalent RBMRNA-405 vaccine in the SARSCoV-2 variant challenge. Results: Results showed that the RBMRNA-405 vaccine could generate broader neutralizing antibody responses against both Wuhan-Hu-1 and other SARS-CoV-2 variants, including Delta, Omicron, Alpha, Beta, and Gamma. RBMRNA-405 efficiently blocked infectious viral replication and lung injury in both Omicron- and Delta-challenged K18-ACE2 mice. Conclusion: Our data suggest that RBMRNA-405 is a promising bivalent SARS-CoV-2 vaccine with broad-spectrum efficacy for further clinical development.

Current Strategies for Engineered Vascular Grafts and Vascularized Tissue Engineering.

Blood vessels not only transport oxygen and nutrients to each organ, but also play an important role in the regulation of tissue regeneration. Impaired or occluded vessels can result in ischemia, tissue necrosis, or even life-threatening events. Bioengineered vascular grafts have become a promising alternative treatment for damaged or occlusive vessels. Large-scale tubular grafts, which can match arteries, arterioles, and venules, as well as meso- and microscale vasculature to alleviate ischemia or prevascularized engineered tissues, have been developed. In this review, materials and techniques for engineering tubular scaffolds and vasculature at all levels are discussed. Examples of vascularized tissue engineering in bone, peripheral nerves, and the heart are also provided. Finally, the current challenges are discussed and the perspectives on future developments in biofunctional engineered vessels are delineated.

Dipeptidyl peptidase 4 as a potential serum biomarker for disease activity and treatment response in rheumatoid arthritis.

BACKGROUND: The treatment of rheumatoid arthritis (RA) related to the disease activity. However, the lack of highly sensitive and simplified markers limits the evaluation of disease activity. We sought to explore potential biomarkers associated with disease activity and treatment response in RA. METHODS: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomic analysis was performed to determine the differentially expressed proteins (DEPs) in serum collected from RA patients with moderate or high disease activity (determined by DAS28) before and after 24 weeks of treatment. Bioinformatic analysis were performed for DEPs and hub proteins. In the validation cohort, 15 RA patients were enrolled. Key proteins were validated by enzyme-linked immunosorbent assay (Elisa), correlation analysis and ROC curve. RESULTS: We identified 77 DEPs. The DEPs enriched in humoral immune response, blood microparticle, and serine-type peptidase activity. KEGG enrichment analysis displayed that the DEPs were significantly enriched in cholesterol metabolism and complement and coagulation cascades. Activated CD4 + T cell, T follicular helper cell, natural killer cell, and plasmacytoid dendritic cell significantly increased after treatment. Fifteen hub proteins were screened out. Among them, dipeptidyl peptidase 4 (DPP4) was the most significant protein associated with clinical indicators and immune cells. Serum concentration of DPP4 was testified to significantly increase after treatment and inversely correlate with disease activity indicators (ESR, CRP, DAS28-ESR, DAS28-CRP, CDAI, SDAI). Significant reduction was found in the serum CXC chemokine ligand10 (CXC10) and CXC chemokine receptor 3 (CXCR3) after treatment. CONCLUSIONS: Overall, our results suggest that serum DPP4 might be a potential biomarker for disease activity assessment and treatment response of RA.

Construction of Smart Biomaterials for Promoting Diabetic Wound Healing.

Diabetes mellitus is a complicated metabolic disease that has become one of the fastest-growing health crises in modern society. Diabetic patients may suffer from various complications, and diabetic foot is one of them. It can lead to increased rates of lower-extremity amputation and mortality, even seriously threatening the life and health of patients. Because its healing process is affected by various factors, its management and treatment are very challenging. To address these problems, smart biomaterials have been developed to expedite diabetic wound closure and improve treatment outcomes. This review begins with a discussion of the basic mechanisms of wound recovery and the limitations of current dressings used for diabetic wound healing. Then, the categories and characteristics of the smart biomaterial scaffolds, which can be utilized as a delivery system for drugs with anti-inflammatory activity, bioactive agency, and antibacterial nanoparticles for diabetic wound treatment were described. In addition, it can act as a responsive system to the stimulus of the pH, reactive oxygen species, and glucose concentration from the wound microenvironment. These results show that smart biomaterials have an enormous perspective for the treatment of diabetic wounds in all stages of healing. Finally, the advantages of the construction of smart biomaterials are summarized, and possible new strategies for the clinical management of diabetic wounds are proposed.

Synthesis of 2-iminothiazolidin-4-ones via copper-catalyzed [2 + 1 + 2] tandem annulation.

In this paper, an efficient synthesis of 2-iminothiazolidin-4-ones through a copper-catalyzed tandem annulation reaction of alkyl amines, isothiocyanates and diazo acetates is presented. Notable advantages of this [2 + 1 + 2] cyclization methodology include readily accessible starting materials, simple operation, mild reaction conditions, high yields, step-economy and diverse functional group tolerance. In addition, the reaction is applicable to the gram scale synthesis and the preparation of bioactive molecules.

Low glutaminase and glycolysis correlate with a high transdifferentiation efficiency in mouse cortex.

Both exogenous transcriptional factors and chemical-defined medium can transdifferentiate astrocytes into functional neurons. However, the regional preference for such transdifferentiation has not been fully studied. A previously reported 5C medium was infused into the mouse cortex and striatum to determine the regional preference for transdifferentiation from astrocytes to neurons. The numbers of NeuN+ GFAP+ EdU+ cells (intermediates) and NeuN+ EdU+ cells (end products) were determined by immunofluorescence to explore the regional preference of transdifferentiation. In addition, to optimize the delivery of the transdifferentiation medium, three key growth factors, insulin, bFGF and transferrin, were loaded onto chitosan nanoparticles, mixed with gelatin methacryloyl and tested in animals with motor cortex injury. A higher transdifferentiation efficiency was identified in the mouse cortex. Differences in cellular respiration and the balance between glutaminase (Gls) and glutamine synthetase were confirmed to be key regulators. In addition, the sustained drug release system induced transdifferentiation of cortex astrocytes both in vivo and in vitro, and partially facilitated the behaviour recovery of mice with motor cortex injury. We also applied this method in pigs and obtained consistent results. In summary, low Gls and glycolysis can be used to predict high transdifferentiation efficiency, which may be useful to identify better indications for the current transdifferentiation system. In addition, the current drug delivery system has the potential to treat diseases related to cortex injuries.

Chemically modified small interfering RNA targeting Hedgehog signaling pathway for rheumatoid arthritis therapy.

Rheumatoid arthritis (RA) is an inflammatory disease that leads to disability; however, existing therapies are still unsatisfactory. Activated fibroblast-like synoviocytes (FLSs) play an essential role in synovitis formation and joint destruction in RA. The Hedgehog signaling pathway is aberrantly activated and contributes to the aggressive phenotype of RA-FLSs. However, it remains uncertain whether inhibiting Smoothened (SMO), a critical component of the Hedgehog signaling pathway, is an effective treatment for RA. Here, we design a series of small interfering RNAs (siRNAs) that specifically target the SMO gene. With precise chemical modifications, siRNAs' efficacy and stability are significantly improved, and the off-target effects are minimized. The optimized chemically modified siRNA (si-S1A3-Chol) decreases RA-FLS proliferation and invasiveness without the transfection reagent. Furthermore, si-S1A3-Chol injected intra-articularly effectively alleviates joint destruction and improves motor function in collagen-induced arthritis mouse models. Consequently, our results demonstrate that chemically modified siRNA targeting the Hedgehog signaling pathway may be a potential therapy for RA.

Harnessing enhanced CRISPR/Cas12a trans-cleavage activity with extended reporters and reductants for early diagnosis of Helicobacter pylori, the causative agent of peptic ulcers and stomach cancer.

Developing rapid and non-invasive diagnostics for Helicobacter pylori (HP) is imperative to prevent associated diseases such as stomach gastritis, ulcers, and cancers. Owing to HP strain heterogeneity, not all HP-infected individuals incur side effects. Cytotoxin-associated gene A (CagA), and vacuolating cytotoxin A (VacA) genes predominantly drive HP pathogenicity. Therefore, diagnosing CagA and VacA genotypes could alert active infection and decide suitable therapeutics. We report an enhanced LbCas12a trans-cleavage activity with extended reporters and reductants (CEXTRAR) for early detection of HP. We demonstrate that extended ssDNA reporter acts as an excellent signal amplifier, making it a potential alternative substrate for LbCas12a collateral activity. Through a systematic investigation of various buffer components, we demonstrate that reductants improve LbCas12a trans-cleavage activity. Overall, our novel reporter and optimal buffer increased the trans-cleavage activity to an order of 16-fold, achieving picomolar sensitivity (171 pM) without target pre-amplification. Integrated with loop-mediated isothermal amplification (LAMP), CEXTRAR successfully attained attomolar sensitivity for HP detection using real-time fluorescence (43 and 96 aM), in-tube fluorescence readouts (430 and 960 aM), and lateral flow (4.3 and 9.6 aM) for CagA and VacA, respectively. We also demonstrate a rapid 2-min Triton X-100 lysis for clinical sample analysis, which could provide clinicians with actionable information for rapid diagnosis. CEXTRAR could potentially spot the 13C urea breath test false-negatives. For the first time, our study unveils an experimental outlook to manipulate reporters and reconsider precise cysteine substitution via protein engineering for Cas variants with enhanced catalytic activities for use in diagnostics and genetic engineering.

Highly Diastereo- and Enantioselective Formal [4 + 2] Cyclization of Nitroalkenes and Unsaturated Ketoesters under Phase-Transfer Catalysis.

A highly diastereo- and enantioselective formal [4 + 2] cyclization of α,ß-unsaturated ketoesters with nitroalkenes through a tandem asymmetric Michael addition-intramolecular Henry reaction under dihydroquinine-based phase-transfer catalysis, leading to a one-pot construction of four contiguous stereochemical centers and multiple functional groups with excellent diastereo- and enantioselectivities in high yields, has been developed. The ee values of some products were increased to ∼100% in good yields after one crystallization.

Immunization with a Prefusion SARS-CoV-2 Spike Protein Vaccine (RBMRNA-176) Protects against Viral Challenge in Mice and Nonhuman Primates.

There is an urgent need for a broad-spectrum and protective vaccine due to the emergence and rapid spreading of more contagious SARS-CoV-2 strains. We report the development of RBMRNA-176, a pseudouridine (Ψ) nucleoside-modified mRNA-LNP vaccine encoding pre-fusion stabilized trimeric SARS-CoV-2 spike protein ectodomain, and evaluate its immunogenicity and protection against virus challenge in mice and nonhuman primates. A prime-boost immunization with RBMRNA-176 at intervals of 21 days resulted in high IgG titers (over 1:819,000 endpoint dilution) and a CD4+ Th1-biased immune response in mice. RBMRNA-176 vaccination induced pseudovirus-neutralizing antibodies with IC50 ranging from 1:1020 to 1:2894 against SARS-CoV-2 spike pseudotyped wild-type and variant viruses, including Alpha, Beta, Gamma, and Kappa. Moreover, significant control of viral replication and histopathology in lungs was observed in vaccinated mice. In nonhuman primates, a boost given by RBMRNA-176 on day 21 after the prime induced a persistent and sustained IgG response. RBMRNA-176 vaccination also protected macaques against upper and lower respiratory tract infection, as well as lung injury. Altogether, these findings support RBMRNA-176 as a vaccine candidate for prevention of COVID-19.

Amphiphilic and fatigue-resistant organohydrogels for small-diameter vascular grafts.

Hydrogels are used in vascular tissue engineering because of their good biocompatibility. However, most natural hydrogels exhibit high swelling ratio, poor mechanical stability, and low durability, which are key limitations for wider applications. Amphiphilic and fatigue-resistant organohydrogels were fabricated here via the click chemical reaction of unsaturated functional microbial polyhydroxyalkanoates and polyethylene glycol diacrylate and a combination of two-dimensional material graphdiyne. These organohydrogels were maintained stable in body fluids over time, and their tensile moduli remained unchanged after more than 2000 cycles of cyclic stretching. The tubular scaffolds presented good biocompatibility and perfusion in vitro. After transplantation in vivo, the vascular grafts exhibited obvious cell infiltration and tissue regeneration, having a higher patency rate than the control group in 3 months. This fabrication method provides a strategy of improving and promoting the application of organohydrogels as implant materials for small-diameter vascular graft.

Proteome Profiling Identifies Serum Biomarkers in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) causes serious disability and productivity loss, and there is an urgent need for appropriate biomarkers for diagnosis, treatment assessment, and prognosis evaluation. To identify serum markers of RA, we performed mass spectrometry (MS)-based proteomics, and we obtained 24 important markers in normal and RA patient samples using a random forest machine learning model and 11 protein-protein interaction (PPI) network topological analysis methods. Markers were reanalyzed using additional proteomics datasets, immune infiltration status, tissue specificity, subcellular localization, correlation analysis with disease activity-based diagnostic indications, and diagnostic receiver-operating characteristic analysis. We discovered that ORM1 in serum is significantly differentially expressed in normal and RA patient samples, which is positively correlated with disease activity, and is closely related to CD56dim natural killer cell, effector memory CD8+T cell, and natural killer cell in the pathological mechanism, which can be better utilized for future research on RA. This study supplies a comprehensive strategy for discovering potential serum biomarkers of RA and provides a different perspective for comprehending the pathological mechanism of RA, identifying potential therapeutic targets, and disease management.

Silence of a dependence receptor CSF1R in colorectal cancer cells activates tumor-associated macrophages.

BACKGROUND: Colony-stimulating factor 1 receptor (CSF1R), a classic tyrosine kinase receptor, has been identified as a proto-oncogene in multiple cancers. The CSF1/CSF1R axis is essential for the survival and differentiation of M2-phenotype tumor-associated macrophages (M2 TAMs). However, we found here that the CSF1R expression was abnormally down-regulated in colorectal cancer (CRC), and its biological functions and underlying mechanisms have become elusive in CRC progression. METHODS: The expression of class III receptor tyrosine kinases in CRC and normal intestinal mucosa was accessed using The Cancer Genome Atlas and Gene Expression Omnibus datasets and was further validated by our tested cohort. CSF1R was reconstructed in CRC cells to identify its biological functions in vitro and in vivo. We compared CSF1R expression and methylation differences between CRC cells and macrophages. Furthermore, a co-culture system was used to mimic a competitive mechanism between CSF1R-overexpressed CRC cells and M2-like macrophages. We utilized a CSF1R inhibitor PLX3397 to ablate M2 TAMs and evaluated its efficacy on CRC treatment in animal models. RESULTS: We found here that the CSF1R is silenced in CRC, and the reintroduced expression of the receptor in CRC cells can be cleaved by caspases and constrain tumor growth in vitro and in vivo, functioning as a tumor suppressor gene. We further identified CSF1R as a novel dependence receptor, which has the potential to act as either a tumor suppressor gene or an oncogene, depending on its activated state. In CRC tumors, CSF1R expression is enriched in TAMs, and its expression is associated with poor prognosis in patients ith CRC. In a co-culture system, CRC cells expressing CSF1R compete with M2-like macrophages for CSF1R ligands, resulting in a decrease in CSF1R activation and cell proliferation in macrophages. Blocking CSF1R by PLX3397 could deplete M2 TAMs and augments CD8+ T cell infiltration, effectively inhibiting tumor growth and metastasis and improving responses to chemotherapy and immunotherapy. CONCLUSION: Our findings revealed that CSF1R is a novel identified dependence receptor silenced in CRC. The silence abalienates its ligands to stimulate CSF1R expressed on M2 TAMs, which is an appealing therapeutic target for M2 TAM depletion and CRC treatment.

Hair follicle-derived mesenchymal stem cells decrease alopecia areata mouse hair loss and reduce inflammation around the hair follicle.

BACKGROUND: Alopecia areata (AA) is a common autoimmune hair loss disease with increasing incidence. Corticosteroids are the most widely used for hair loss treatment; however, long-term usage of hormonal drugs is associated with various side effects. Mesenchymal stem cells (MSCs) therapy has been studied extensively to curb autoimmune diseases without affecting immunity against diseases. METHODS: Hair follicle-derived MSCs (HF-MSCs) were harvested from the waste material of hair transplants, isolated and expanded. The therapeutic effect of HF-MSCs for AA treatment was investigated in vitro AA-like hair follicle organ model and in vivo C3H/HeJ AA mice model. RESULTS: AA-like hair follicle organ in vitro model was successfully established by pre-treatment of mouse vibrissa follicles by interferon-γ (IFN-γ). The AA-like symptoms were relieved when IFN-γ induced AA in vitro model was co-cultured with HF-MSC for 2 days. In addition, when skin grafted C3H/HeJ AA mice models were injected with 106 HF-MSCs once a week for 3 weeks, the transcription profiling and immunofluorescence analysis depicted that HF-MSCs treatment significantly decreased mouse hair loss and reduced inflammation around HF both in vitro and in vivo. CONCLUSIONS: This study provides a new therapeutic approach for alopecia areata based on HF-MSCs toward its future clinical application.

Dendrimer end-terminal motif-dependent evasion of human complement and complement activation through IgM hitchhiking.

Complement is an enzymatic humoral pattern-recognition defence system of the body. Non-specific deposition of blood biomolecules on nanomedicines triggers complement activation through the alternative pathway, but complement-triggering mechanisms of nanomaterials with dimensions comparable to or smaller than many globular blood proteins are unknown. Here we study this using a library of <6 nm poly(amido amine) dendrimers bearing different end-terminal functional groups. Dendrimers are not sensed by C1q and mannan-binding lectin, and hence do not trigger complement activation through these pattern-recognition molecules. While, pyrrolidone- and carboxylic acid-terminated dendrimers fully evade complement response, and independent of factor H modulation, binding of amine-terminated dendrimers to a subset of natural IgM glycoforms triggers complement activation through lectin pathway-IgM axis. These findings contribute to mechanistic understanding of complement surveillance of dendrimeric materials, and provide opportunities for dendrimer-driven engineering of complement-safe nanomedicines and medical devices.

Biosimilar or Not: Physicochemical and Biological Characterization of MabThera and Its Two Biosimilar Candidates.

The development of therapeutic biosimilar antibodies has become an important driving force of the modern biopharmaceutical industry. In this study, physiochemical characteristics (amino acid sequence, intact/subunit molecular weight, isoelectric point, post-translation modification, and disulfide linkage pattern), purity (charge variants, high and low molecular weight variants), antigen binding activity, Fc receptor binding affinity and Fc-effector function (CDC and ADCC) were analyzed by using an extensive set of state-of-the-art and orthogonal analytical technologies to provide a comprehensive characterization of the innovative product rituximab and two biosimilar candidates. The similarity study showed that biosimilar candidate 1 (BC1) and the reference product (RP) MabThera had an identical protein amino acid sequences and highly similar primary structures along with similar purity, heterogeneity profiles, antigen binding activity, Fc receptor binding affinity, and Fc-effector functions. Biosimilar candidate 2 (BC2), which had an amino acid replacement at a constant region, a different N-glycosylation profiling, and purity, was not analytically similar to RP. Although BC2 showed improvement such as an increased level of afucose, another IgG1 allotype, and similar biological activities, it was not recommended to be applied as a biosimilar compound in drug registration because the biosimilar manufacturer must first show that its primary structure was identical to that of RP. Our physicochemical characterizations and bioassay comparability study provided a deepened understanding of the structure-function relationship of quality attributes.

Poly(lactide-co-glycolide) Nanoparticles Mediate Sustained Gene Silencing and Improved Biocompatibility of siRNA Delivery Systems in Mouse Lungs after Pulmonary Administration.

Pulmonary delivery of small interfering RNA (siRNA)-based drugs is promising in treating severe lung disorders characterized by the upregulated expression of disease-causing genes. Previous studies have shown that the sustained siRNA release in vitro can be achieved from polymeric matrix nanoparticles based on poly(lactide-co-glycolide) (PLGA) loaded with lipoplexes (LPXs) composed of cationic lipid and anionic siRNA (lipid-polymer hybrid nanoparticles, LPNs). Yet, the in vivo efficacy, potential for prolonging the pharmacological effect, disposition, and safety of LPNs after pulmonary administration have not been investigated. In this study, siRNA against enhanced green fluorescent protein (EGFP-siRNA) was either assembled with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) to form LPX or co-entrapped with DOTAP in PLGA nanoparticles to form LPNs. The disposition and clearance of LPXs and LPNs in mouse lungs were studied after intratracheal administration by using single-photon emission computed tomography/computed tomography (SPECT/CT) and gamma counting. Fluorescence spectroscopy, Western blot, and confocal laser scanning microscopy were used to evaluate the silencing of the EGFP expression mediated by the LPXs and LPNs after intratracheal administration to transgenic mice expressing the EGFP gene. The in vivo biocompatibility of LPXs and LPNs was investigated by measuring the cytokine level, total cell counts in bronchoalveolar lavage fluid, and observing the lung tissue histology section. The results showed that the silencing of the EGFP expression mediated by LPNs after pulmonary administration was both prolonged and enhanced as compared to LPXs. This may be attributed to the sustained release characteristics of PLGA, and the prolonged retention in the lung tissue of the colloidally more stable LPNs in comparison to LPXs, as indicated by SPECT/CT. The presence of PLGA effectively alleviated the acute inflammatory effect of cationic lipids to the lungs. This study suggests that PLGA-based LPNs may present an effective formulation strategy to mediate sustained gene silencing effects in the lung via pulmonary administration.

Integrin-Targeted, Short Interfering RNA Nanocomplexes for Neuroblastoma Tumor-Specific Delivery Achieve MYCN Silencing with Improved Survival.

The authors aim to develop siRNA therapeutics for cancer that can be administered systemically to target tumors and retard their growth. The efficacy of systemic delivery of siRNA to tumors with nanoparticles based on lipids or polymers is often compromised by their rapid clearance from the circulation by the liver. Here, multifunctional cationic and anionic siRNA nanoparticle formulations are described, termed receptor-targeted nanocomplexes (RTNs), that comprise peptides for siRNA packaging into nanoparticles and receptor-mediated cell uptake, together with lipids that confer nanoparticles with stealth properties to enhance stability in the circulation, and fusogenic properties to enhance endosomal release within the cell. Intravenous administration of RTNs in mice leads to predominant accumulation in xenograft tumors, with very little detected in the liver, lung, or spleen. Although non-targeted RTNs also enter the tumor, cell uptake appears to be RGD peptide-dependent indicating integrin-mediated uptake. RTNs with siRNA against MYCN (a member of the Myc family of transcription factors) in mice with MYCN-amplified neuroblastoma tumors show significant retardation of xenograft tumor growth and enhanced survival. This study shows that RTN formulations can achieve specific tumor-targeting, with minimal clearance by the liver and so enable delivery of tumor-targeted siRNA therapeutics.

Cationic Nanomaterials for Autoimmune Diseases Therapy.

Cationic nanomaterials are defined as nanoscale structures smaller than 100 nm bearing positive charges. They have been investigated to apply to many aspects including clinical diagnosis, gene delivery, drug delivery, and tissue engineering for years. Recently, a novel concept has been made to use cationic nanomaterials as cell-free nucleic acid scavengers and inhibits the inflammatory responses in autoimmune diseases. Here, we highlighted different types of cationic materials which have the potential for autoimmune disease treatment and reviewed the strategy for autoimmune diseases therapy based on cationic nanoparticles. This review will also demonstrate the challenges and possible solutions that are encountered during the development of cationic materials-based therapeutics for autoimmune diseases.