Immunostimulatory chimeric protein encapsulated in gelatin nanoparticles elicits protective immunity against Pseudomonas aeruginosa respiratory tract infection.

This study presents the design and fabrication of an innovative vaccine candidate targeting Pseudomonas aeruginosa (P. aeruginosa). The vaccine consists of gelatin nanoparticles (GNPs) encapsulating a chimeric protein (CP) derived from ExoS and OprI proteins from P. aeruginosa. The physicochemical properties of the GNPs were assessed using dynamic light scattering (DLS) and electron microscopy. The toxicity, encapsulation efficacy, release profile, and finally effectiveness of CP-encapsulated GNPs (CP-GNPs) in animal model were investigated. The resulting nano vaccine demonstrated uniform spherical particles with an average size of 135 nm and encapsulation efficiency of 85 %. The release assay revealed that 23 % of the antigen was released from the CP-GNPs after 20 days. The GNPs did not exhibit any toxic effects on L929 cells in vitro. The formulation induced both systemic and mucosal antibody responses. Additionally, CP-GNPs stimulated cytokine responses, including IFN-γ, IL-4, and IL-17, indicating the induction of both humoral (Th2) and cellular (Th1) responses. The CP-encapsulated GNPs formulation effectively protected mice lungs against experimental respiratory tract infection and reduced colony count and inflammation. These findings suggest that CP-GNPs holds promise as a potential strategy for preventing respiratory tract infections caused by P. aeruginosa. Further research is needed to explore its clinical application.

In silico and in vivo Investigations of the Immunoreactivity of Klebsiella pneumoniae OmpA Protein as a Vaccine Candidate.

Background: The growing threat of antibiotic resistance and Klebsiella pneumoniae infection in healthcare settings highlights the urgent need for innovative solutions, such as vaccines, to address these challenges. This study sought to assess the potential of using K. pneumoniae OmpA as a vaccine candidate through both in silico and in vivo analyses. Methods: The study examined the OmpA protein sequence for subcellular localization, antigenicity, allergenicity, similarity to the human proteome, physicochemical properties, B-cell epitopes, MHC binding sites, tertiary structure predictions, molecular docking, and immune response simulations. The ompA gene was cloned into the pET-28a (+) vector, expressed, purified and confirmed using Western blotting analysis. IgG levels in the serum of the immunized mice were measured using ELISA with dilutions ranging from 1:100 to 1:6400, targeting rOmpA and K. pneumoniae ATCC 13883. The sensitivity and specificity of the ELISA method were also assessed. Results: The bioinformatics analysis identified rOmpA as a promising vaccine candidate. The immunized group demonstrated significant production of specific total IgG antibodies against rOmpA and K. pneumoniae ATCC1 13883, as compared to the control group (p < 0.0001). The titers of antibodies produced in response to bacterial exposure did not show any significant difference when compared to the anti-rOmpA antibodies (p > 0.05). The ELISA test sensitivity was 1:3200, and the antibodies in the serum could accurately recognize K. pneumoniae cells. Conclusion: This study is a significant advancement in the development of a potential vaccine against K. pneumoniae that relies on OmpA. Nevertheless, additional experimental analyses are required.

Polydopamine-based nano adjuvant as a promising vaccine carrier induces significant immune responses against Acinetobacter baumannii-associated pneumonia.

The objective of this study was to assess the effectiveness of polydopamine nanoparticles (PDANPs) as a delivery system for intranasal antigen administration to prevent Acinetobacter baumannii (A. baumannii)-associated pneumonia. In the in vitro phase, the conserved outer membrane protein 22 (Omp22)-encoding gene of A. baumannii was cloned, expressed, and purified, resulting in the production of recombinant Omp22 (rOmp22), which was verified using western blot. PDANPs were synthesized using dopamine monomers and loaded with rOmp22 through physical adsorption. The rOmp22-loaded PDANPs were characterized in terms of size, size distribution, zeta potential, field emission scanning electron microscopy (FESEM), loading capacity, Fourier transform infrared spectroscopy (FTIR), release profile, and cytotoxicity. In the in vivo phase, the adjuvant effect of rOmp22-loaded PDANPs was evaluated in terms of eliciting immune responses, including humoral and cytokine levels (IL-4, IL-17, and IFN-γ), as well as protection challenge. The rOmp22-loaded PDANPs were spherical with a size of 205 nm, a zeta potential of -14 mV, and a loading capacity of approximately 35.7 %. The released rOmp22 from nontoxic rOmp22-loaded PDANPs over 20 days was approximately 41.5 %, with preserved rOmp22 integrity. The IgG2a/IgG1 ratio and IFN-γ levels were significantly higher in immunized mice with rOmp22-loaded-PDANPs than in rOmp22-alum, naive Omp22, and control groups. Furthermore, rOmp22-loaded PDANPs induced effective protection against infection in the experimental challenge and showed more normal structures in the lung histopathology assay. The results of this study suggest the potential of PDANPs as a nano-adjuvant for inducing strong immune responses to combat A. baumannii.

Conductive hydrogels based on tragacanth and silk fibroin containing dopamine functionalized carboxyl-capped aniline pentamer: Merging hemostasis, antibacterial, and anti-oxidant properties into a multifunctional hydrogel for burn wound healing.

Hydrogels possessing both conductive characteristics and notable antibacterial and antioxidant properties hold considerable significance within the realm of wound healing and recovery. The object of current study is the development of conductive hydrogels with antibacterial and antioxidant properties, emphasizing their potential for effective wound healing, especially in treating third-degree burns. For this purpose, various conductive hydrogels are developed based on tragacanth and silk fibroin, with variable dopamine functionalized carboxyl-capped aniline pentamer (CAP@DA). The FTIR analysis confirms that the CAP powder was successfully synthesized and modified with DA. The results show that the incorporation of CAP@DA into hydrogels can increase the porosity and swellability of the hydrogels. Additionally, the mechanical and viscoelastic properties of the hydrogels are also improved. The release of vancomycin from the hydrogels is sustained over time, and the hydrogels are effective in inhibiting the growth of Methicillin-resistant Staphylococcus aureus (MRSA). In vitro cell studies of the hydrogels show that all hydrogels are biocompatible and support cell attachment. The hydrogels' tissue adhesiveness yielded a satisfactory hemostatic outcome in a rat-liver injury model. The third-degree burn was created on the dorsal back paravertebral region of the rats and then grafted with hydrogels. The burn was monitored for 3, 7, and 14 days to evaluate the efficacy of the hydrogel in promoting wound healing. The hydrogels revealed treatment effect, resulting in enhancements in wound closure, dermal collagen matrix production, new blood formation, and anti-inflammatory properties. Better results were obtained for hydrogel with increasing CAP@DA. In summary, the multifunctional conducive hydrogel, featuring potent antibacterial properties, markedly facilitated the wound regeneration process.

Efficient three-dimensional (3D) human bone differentiation on quercetin-functionalized isotropic nano-architecture chitinous patterns of cockroach wings.

Developing cost-effective, biocompatible scaffolds with nano-structured surface that truthfully replicate the physico-(bio)chemical and structural properties of bone tissue's extracellular matrix (ECM) is still challenging. In this regard, surface functionalization of natural scaffolds to enhance capability of mimicking 3D niches of the bone tissue has been suggested as a solution. In the current study, we aimed to investigate the potential of chitin-based cockroach wings (CW) as a natural scaffold for bone tissue engineering. To raise the osteogenic differentiation capacity of such a scaffold, a quercetin coating was also applied (hereafter this scaffold is referred as QCW). Moreover, the QCW scaffold exhibited effective antibacterial properties against gram-positive S. aureus bacteria. With respect to bone regeneration, the QCW scaffold optimally induced the differentiation of adipose-derived human mesenchymal stem cells (AD-hMSCs) into osteoblasts, as validated by mineralization assays, alkaline phosphatase (ALP) activity measurements, expression of pre-osteocyte marker genes, and immunocytochemical staining. Confirmation of the potent biocompatibility and physicochemical characteristics of the QCW scaffold through a series of in vitro and in vivo analysis revealed that surface modification had significant effect on multi-purpose features of obtained scaffold. Altogether, surface modification of QCW made it as an affordable bioinspired scaffold for bone tissue engineering.

Design and fabrication of a vaccine candidate based on rOmpA from Klebsiella pneumoniae encapsulated in silk fibroin-sodium alginate nanoparticles against pneumonia infection.

The present study describes the design and fabrication of a novel vaccine candidate based on the outer membrane protein A (rOmpA) from Klebsiella pneumoniae (K. pneumoniae) encapsulated in silk fibroin-sodium alginate nanoparticles (SF-SANPs) against K. pneumoniae-mediated pneumonia. The physicochemical properties, toxicity, release profile, and in vivo potency of SF-SANPs encapsulated with rOmpA were evaluated. The spherical nano vaccine was created with an average particle size of 160 nm and an encapsulation efficiency of 80 %. Antigen release from SF-SANPs was 40 % after 22 days release assay. The SF-SANPs showed a zeta potential of -24.8 mV and had no toxic effect on the L929 cells in vitro. It was found that SF-SANPs in the vaccine formulation promoted systemic and mucosal antibodies and also stimulated cytokine responses, inducing both humoral (Th2) and cellular (Th1) immune responses, with a Th1-polarized response. The vaccine candidate was effective in protecting the mice lung against experimental pneumonia and reducing inflammation. These findings suggest that the rOmpA-based vaccine encapsulated in SF-SANPs could be a promising strategy for preventing pneumonia caused by K. pneumoniae.

Alginate/gum arabic-based biomimetic hydrogel enriched with immobilized nerve growth factor and carnosine improves diabetic wound regeneration.

Diabetic foot ulcers (DFUs) often remain untreated because they are difficult to heal, caused by reduced skin sensitivity and impaired blood vessel formation. In this study, we propose a novel approach to manage DFUs using a multifunctional hydrogel made from a combination of alginate and gum arabic. To enhance the healing properties of the hydrogel, we immobilized nerve growth factor (NGF), within specially designed mesoporous silica nanoparticles (MSN). The MSNs were then incorporated into the hydrogel along with carnosine (Car), which further improves the hydrogel's therapeutic properties. The hydrogel containing the immobilized NGF (SiNGF) could control the sustain release of NGF for >21 days, indicating that the target hydrogel (AG-Car/SiNGF) can serve as a suitable reservoir managing diabetic wound regeneration. In addition, Car was able to effectively reduce inflammation and significantly increase angiogenesis compared to the control group. Based on the histological results obtained from diabetic rats, the target hydrogel (AG-Car/SiNGF) reduced inflammation and improved re-epithelialization, angiogenesis, and collagen deposition. Specific staining also confirmed that AG-Car/SiNGF exhibited improved tissue neovascularization, transforming growth factor-beta (TGFß) expression, and nerve neurofilament. Overall, our research suggests that this newly developed composite system holds promise as a potential treatment for non-healing diabetic wounds.

Injectable hydrogel based on silk fibroin/carboxymethyl cellulose/agarose containing polydopamine functionalized graphene oxide with conductivity, hemostasis, antibacterial, and anti-oxidant properties for full-thickness burn healing.

Overcoming bacterial infections and promoting wound healing are significant challenges in clinical practice and fundamental research. This study developed a series of enzymatic crosslinking injectable hydrogels based on silk fibroin (SF), carboxymethyl cellulose (CMC), and agarose, with the addition of polydopamine functionalized graphene oxide (GO@PDA) to endow the hydrogel with suitable conductivity and antimicrobial activity. The hydrogels exhibited suitable gelation time, stable mechanical and rheological properties, high water absorbency, and hemostatic properties. Biocompatibility was also confirmed through various assays. After loading the antibiotic vancomycin hydrochloride, the hydrogels showed sustained release and good antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). The fast gelation time and desirable tissue-covering ability of the hydrogels allowed for a good hemostatic effect in a rat liver trauma model. In a rat full-thickness burn wound model, the hydrogels exhibited an excellent treatment effect, leading to significantly enhanced wound closure, collagen deposition, and granulation tissue formation, as well as neovascularization and anti-inflammatory effects. In conclusion, the antibacterial electroactive injectable hydrogel dressing, with its multifunctional properties, significantly promoted the in vivo wound healing process, making it an excellent candidate for full-thickness skin wound healing.

Immunogenic Potential and Therapeutic Efficacy of Multi-Epitope Encapsulated Silk Fibroin Nanoparticles against Pseudomonas aeruginosa-Mediated Urinary Tract Infections.

Pseudomonas aeruginosa (P. aeruginosa) causing urinary tract infections (UTIs) are a major concern among hospital-acquired infections. The need for an effective vaccine that reduces the infections is imperative. This study aims to evaluate the efficacy of a multi-epitope vaccine encapsulated in silk fibroin nanoparticles (SFNPs) against P. aeruginosa-mediated UTIs. A multi-epitope is constructed from nine proteins of P. aeruginosa using immunoinformatic analysis, expressed, and purified in BL21 (DE3) cells. The encapsulation efficiency of the multi-epitope in SFNPs is 85% with a mean particle size of 130 nm and 24% of the encapsulated antigen is released after 35 days. The vaccine formulations adjuvanted with SFNPs or alum significantly improve systemic and mucosal humoral responses and the cytokine profile (IFN-γ, IL-4, and IL-17) in mice. Additionally, the longevity of the IgG response is maintained for at least 110 days in a steady state. In a bladder challenge, mice treated with the multi-epitope admixed with alum or encapsulated in SFNPs demonstrate significant protection of the bladder and kidneys against P. aeruginosa. This study highlights the promising therapeutic potential of a multi-epitope vaccine encapsulated in SFNPs or adjuvanted with alum against P. aeruginosa infections.

Injectable multifunctional hydrogel based on carboxymethylcellulose/polyacrylamide/polydopamine containing vitamin C and curcumin promoted full-thickness burn regeneration.

Burn injuries are a major global problem, with a high risk of infection and mortality. This study aimed to develop an injectable hydrogel for wound dressings, composed of sodium carboxymethylcellulose/polyacrylamide/polydopamine containing vitamin C (CMC/PAAm/PDA VitC) for its antioxidant and antibacterial properties. Simultaneously, silk fibroin/alginate nanoparticles (SF/SANPs) loaded with curcumin (SF/SANPs CUR) were incorporated into the hydrogel to enhance wound regeneration and reduce bacterial infection. The hydrogels were fully characterized and tested in vitro and in preclinical rat models for biocompatibility, drug release, and wound healing efficacy. Results showed stable rheological properties, appropriate swelling and degradation ratios, gelation time, porosity, and free radical scavenging capacity. Biocompatibility was confirmed through MTT, lactate dehydrogenase, and apoptosis evaluations. Hydrogels containing curcumin demonstrated antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). In the preclinical study, hydrogels containing both drugs showed superior support for full-thickness burn regeneration, with improved wound closure, re-epithelialization, and collagen expression. The hydrogels also showed neovascularization and anti-inflammatory effects, as confirmed by CD31 and TNF-α markers. In conclusion, these dual drug-delivery hydrogels showed significant potential as wound dressings for full-thickness wounds.

Dual drug delivery system of teicoplanin and phenamil based on pH-sensitive silk fibroin/sodium alginate hydrogel scaffold for treating chronic bone infection.

For effective treatment of infected bone, it is essential to use local drug delivery systems with the ability to deliver both antibiotics and osteoinductive factors. Herein, a pH-sensitive silk fibroin (SF)/sodium alginate (SA) hydrogel scaffolds containing teicoplanin (TEC) and phenamil (PM) loaded SF nanoparticles (PMSFNPS) are introduced for treating chronic osteomyelitis. The TEC and PM showed a sustained- and pH-sensitive release behavior from SF/SA hydrogel. The higher release rate was seen in an alkaline pH in comparison to neutral and acidic pH during 10 days. The eluted TEC maintained its antibacterial activity of >75 % during 35 days and in three different pH values (5.5, 7.4, and 8.5). The cellular study indicated that the scaffolds containing PMSFNPs could promote the cell viability, ALP activity, and matrix mineralization. Moreover, the in vivo effectiveness of hydrogel scaffolds were analyzed with radiography, histological and Immunohistochemistry evaluations. The lower infection and higher regeneration were observed in methicillin-resistant Staphylococcus aureus (MRSA) infected rat bone treated with hydrogel scaffold containing PMSFNPs and TEC compared to other groups. Consequently, this dual-drug delivery system could be a hopeful approach for effective treatment of chronic bone infection.

Advanced Multifunctional Wound Dressing Hydrogels as Drug Carriers.

Skin injuries, especially chronic wounds, remain a significant healthcare system problem. The number of burns, diabetic patients, pressure ulcers, and other damages is also growing, particularly in elderly populations. Several investigations are pursued in designing more effective therapeutics for treating different wound injuries. These efforts have resulted in developing multifunctional wound dressings to improve wound repair. For this, preparing multifunctional dressings using various methods has provided a new attitude to support effective skin regeneration. This review focuses on the recent developments in designing multifunctional hydrogel dressings with hemostasis, adhesiveness, antibacterial, and antioxidant properties.

Nanocomposite pectin fibers incorporating folic acid-decorated carbon quantum dots.

Pectin has recently attracted increasing attention as an alternative biomaterial commonly used in biomedical and pharmaceutical fields. It shows several promising properties, including good biocompatibility, health benefits, nontoxicity, and biodegradation. In this research, novel nanocomposite fibers composed of folic acid-decorated carbon dots (CDs) in pectin/PEO matrix were fabricated using the electrospinning technique, which was never reported previously. Nitrogen-doped and nitrogen, sulfur-doped CDs were synthesized with average diameters of 2.74 nm and 2.17 nm using the one-step hydrothermal method, studied regarding their physicochemical, optical, and biocompatibility properties. The relative Quantum yields of N-CDs and N, S doped CDs were measured to be 54.7 % and 30.2 %, respectively. Nanocomposite fibers containing CDs were prepared, and their morphology, physicochemical properties, conductivity, drug release behavior, and cell viability were characterized. The results indicated that CDs improve fibrous scaffolds' tensile strength from 13.74 to 35.22 MPa while maintaining comparable extensibility. Furthermore, by incorporation of CDs in the prepared fibers conductivity enhanced from 8.69 × 10-9 S·m-1 to 1.36 × 10-4 S·m-1. The nanocomposite fibrous scaffold was also biocompatible with controlled drug release over 212 h, potentially promising tissue regeneration.

Thermosensitive chitosan/poly(N-isopropyl acrylamide) nanoparticles embedded in aniline pentamer/silk fibroin/polyacrylamide as an electroactive injectable hydrogel for healing critical-sized calvarial bone defect in aging rat model.

Thermosensitive nanoparticles with phase transition abilities have been considered as suitable materials in biomedical fields, especially drug delivery systems. Moreover, electroactive injectable hydrogels supporting bone regeneration of the elderly will highly be desired in bone tissue engineering applications. Herein, thermosensitive nanoparticles were fabricated using chitosan/poly(N-isopropyl acrylamide) for simvastatin acid delivery. The nanoparticles were incorporated into electroactive injectable hydrogels based on aniline pentamer/silk fibroin/polyacrylamide containing vitamin C. The nanoparticles had thermosensitive properties as simvastatin acid had higher release rates at 37 than 23 °C without significant burst release. The hydrogels also revealed an appropriate gelation time, stable mechanical and rheological characteristics, high water absorbency, and proper biodegradability. In vitro studies indicated that the hydrogel was biocompatible and nontoxic, especially those containing drugs. Implantation of the hydrogels containing both simvastatin acid and vitamin C into the critical calvarial bone defect of the aged rat also demonstrated significant enhancement of bone healing after 4 and 8 weeks post-implantation. We found that the electroactive injectable hydrogels containing thermosensitive nanoparticles exhibited great potential for treating bone defects in the elderly rats.

Fabrication of Silk Scaffold Containing Simvastatin-Loaded Silk Fibroin Nanoparticles for Regenerating Bone Defects

Background: In the present study, a tissue engineered silk fibroin (SF) scaffold containing simvastatin-loaded silk fibroin nanoparticles (SFNPs) were used to stimulate the regeneration of the defected bone. Methods: At first, the porous SF scaffold was prepared using freeze-drying. Then simvastatin-loaded SFNPs were made by dissolvation method and embedded in the SF scaffold. Afterwards, the scaffold and the NPs were characterized in terms of physicochemical properties and the ability to release the simvastatin small molecule. Results: The results exhibited that the SF scaffold had a porous structure suitable for releasing the small molecule and inducing the proliferation and attachment of osteoblast cells. SFNPs containing simvastatin had spherical morphology and were 174 ± 4 nm in size with -24.5 zeta potential. Simvastatin was also successfully encapsulated within the SFNPs with 68% encapsulation efficiency. Moreover, the small molecule revealed a sustained release profile from the NPs during 35 days. The results obtained from the in vitro cell-based studies indicated that simvastatin-loaded SFNPs embedded in the scaffold had acceptable capacity to promote the proliferation and alkaline phosphatase production of osteoblast cells while inducing osteogenic matrix precipitation. Conclusion: The SF scaffold containing simvastatin-loaded SFNPs could have a good potential to be used as a bone tissue-engineered construct.

Composite Microgels for Imaging-Monitored Tracking of the Delivery of Vascular Endothelial Growth Factor to Ischemic Muscles.

Monitoring the supply of vascular endothelial growth factor (VEGF) to ischemic tissues provides information on its biodistribution and delivery to meet the requirements of therapeutic angiogenesis and tissue engineering applications. We herein report the use of microfluidically generated microgels containing VEGF-conjugated fluorescent carbon dots (CDs) (VEGF-CDs), a gelatin-phenol conjugate, and silk fibroin for imaging-monitored tracking of VEGF delivery to ischemic muscles. An in vitro release study and a bioactivity assay indicated that the VEGF-CDs were released in a sustained manner with high bioactivity. The microgels showed a high angiogenesis potential, along with a strong fluorescent signal, for the chicken chorioallantoic membrane and chick embryo. Imaging and studies of therapeutic modalities of the composite microgels indicated their effective localization in ischemic tissues and sustained VEGF release, which resulted in enhanced therapeutic angiogenesis of ischemic muscles. This work reveals the success of using VEGF-loaded composite polymer microgels for efficient and monitored VEGF delivery by intramuscular administration for ischemic disease treatment.

Preparation of microfluidic-based pectin microparticles loaded carbon dots conjugated with BMP-2 embedded in gelatin-elastin-hyaluronic acid hydrogel scaffold for bone tissue engineering application.

The controlled delivery of the bone morphogenetic protein-2 (BMP-2) with tracking ability would overcome most of the side effects linked to the burst release and uncontrolled delivery of this growth factor for bone regeneration. Herein, BMP-2-conjugated carbon dots (CDs) was used as noninvasive detection platforms to deliver BMP-2 for therapeutic applications where osteogenesis and bioimaging are both required. With this in mind, the present work aimed to develop a controlled BMP-2-CDs release system using composite scaffolds containing BMP-2-CDs loaded pectin microparticles, which had been optimized for bone regeneration. By using microfluidic approach, we encapsulated BMP-2-CDs in pectin microparticles with narrow size distribution and then incorporated into composite scaffolds composed of gelatin, elastin, and hyaluronic acid. The BMP-2-CDs was released from the composite scaffolds in a sustained fashion for up to 21 days exhibited a high controlled delivery capacity. When tested in vitro with MG-63 cells, these extraction mediums showed the intercellular uptake of BMP-2-CDs and enhanced biological properties and pro-osteogenic effect. By utilizing the pectin microparticles carrying BMP-2-CDs as promising bioimaging agents for growth factor delivery and by tuning the composition of the scaffolds, this platform has immense potential in the field of bone tissue regeneration.

Combination Therapy of Breast Cancer by Codelivery of Doxorubicin and Survivin siRNA Using Polyethylenimine Modified Silk Fibroin Nanoparticles.

Here, polyethylenimine (PEI) modified silk fibroin nanoparticles (SFNPs) were prepared for codelivery of doxorubicin (DOX) and survivin siRNA. The prepared NPs were characterized in terms of stability and structural, functional, and physicochemical properties. Moreover, the ability of the conjugate to escape from the endosome and cellular uptake were assessed. Afterward, the in vivo therapeutic efficacy was analyzed in the mice model. The siRNA loaded PEI-SFNPs showed acceptable size, zeta potential, and stability in serum. It also effectively induced apoptosis in the 4T1 mouse mammary tumor cell line. Cellular uptake and endosomal escape analyses confirmed that PEI-SFNPs containing siRNA could escape from the endosome and accumulate in the cytoplasm of 4T1 cells. Real time-PCR indicated the significant decrease in the expression of survivin mRNA in the 4T1 cell line 48 h postincubation with siRNA loaded PEI-SFNPs. In vivo biodistribution of PEI-SFNPs confirmed higher accumulation of SFNPs in the tumor site compared with other organs. The codelivery systems remarkably reduced the growth rate of breast tumor in the mice model without any obvious weight lost. Histopathological and tunnel staining exhibited more apoptotic tumor cells in the group containing both DOX and survivin siRNA. Tumorigenic breast tissue resected from the animals after treatment with siRNA also exhibited significant suppression of survivin gene. In conclusion, the prepared drug delivery system had an acceptable potential in tumor removal, apoptosis induction in cancer cells, and therapeutic efficacy. Thus, it would be a good candidate for breast cancer therapy.

Nano-adjuvant based on silk fibroin for the delivery of recombinant hepatitis B surface antigen.

Nanotechnology has a vital role in vaccine development. Nano-adjuvants, as robust delivery systems, could stimulate immune responses. Using nanoparticles (NPs) in vaccine formulations enhances the target delivery, immunogenicity, and stability of the antigens. Herein, silk fibroin nanoparticles (SFNPs) were used as a nano-adjuvant for delivering recombinant hepatitis B surface antigen (HBsAg). HBsAg was loaded physically and chemically on the surface of SFNPs. The HBsAg-loaded SFNPs had a spherical morphology. The in vitro release studies showed that HBsAg had a continuous and slow release from SFNPs during 56 days. During this time, ∼45.6% and 34.1% HBsAg was released from physical-SFNPs and chemical-SFNPs, respectively. HBsAg-loaded SFNPs were also stable for six months with slight changes in the size, surface charge, and morphology. The results of circular dichroism (CD) and fluorescence spectroscopy indicated that the released HBsAg preserved the native secondary and tertiary structures. The quantitative cellular uptake study also showed that physical-SFNPs were taken up more into J774A.1 macrophage cells than chemical-SFNPs. After 28 and 56 days post-injection, the immunogenicity studies showed that the specific total IgG, IgG1, and IgG2a levels against HBsAg were significantly higher in the physically loaded group than in the chemically loaded group and commercial hepatitis B vaccine. IgG2a levels were detected only in mice immunized with physical-SFNPs. However, the low levels of IL-4 and IFN-γ were produced in all vaccinated groups and differences in mean values were not significant compared with control groups. Results indicated an improvement in the levels of anti-HBsAg IgG in mice immunized with the physical-SFNPs group compared to other groups.

Electrospun pectin/modified copper-based metal-organic framework (MOF) nanofibers as a drug delivery system.

Pectin has been regarded as a drug carrier accelerating the healing process due to its bioactivities, abundance and lower cost of resources. However, a big challenge related to its practical application is its poor mechanical strength. In this study the modified Cu-based MOF containing Folic acid was synthesized and incorporated in the suitable pectin electrospun nanofibers which not only improved the copper ions release behavior but also made the fiber mat stronger, antibacterial and induce angiogenesis, fibroblast migration, and proliferation due to loaded copper ions and folic acid. The nanofibers composing of 75% pectin and 4000 kDa -PEO were chosen after morphological and mechanical characterization. Finally, the effect of MOF incorporation on the nanocomposite samples was characterized in terms of morphological, physiochemical and biological properties. The nanofibrous mats were evaluated by tensile testing, antibacterial and cytotoxicity. The release behavior of copper ions and folic acid was controlled and their burst release alleviated reducing cytotoxicity in vitro. It was found that the Young's moduli of the pectin nanofibers were improved to 19.13 MPa by the addition of Cu-based MOFs. Moreover, nanocomposite pectin nanofibers were found to be antibacterial and biocompatible. These results demonstrate that MOF-contained pectin nanofibers are promising for biomedical applications.