Calcium Phosphate Nanoparticles Research Articles

Injectable PEG Hydrogels with Tissue-Like Viscoelasticity Formed through Reversible Alendronate-Calcium Phosphate Crosslinking for Cell-Material Interactions.

Synthetic hydrogels provide controllable 3D environments, which can be used to study fundamental biological phenomena. The growing body of evidence that cell behavior depends upon hydrogel stress relaxation creates a high demand for hydrogels with tissue-like viscoelastic properties. Here, we have created a unique platform of synthetic PEG hydrogels in which star-shaped PEG molecules were conjugated with alendronate and/or RGD peptides, attaining modifiable degradability as well as flexible cell adhesion. We identified novel reversible ionic interactions between alendronate and calcium phosphate nanoparticles, leading to versatile viscoelastic properties with varying initial elastic modulus and stress relaxation time. This new crosslinking mechanism provides shear-thinning properties resulting in differential cellular responses between cancer cells and stem cells. The novel hydrogel system is an improved design to the other ionic crosslink platforms and opens new avenues for the development of pathologically relevant cancer models, as well as minimally-invasive approaches for cell delivery for potential regenerative therapies. This article is protected by copyright. All rights reserved.

Multifunctional Nanofibrous Hollow Microspheres for Enhanced Periodontal Bone Regeneration.

Destructive periodontitis destroys alveolar bone and eventually leads to tooth loss. While guided bone regeneration, which is based on creating a physical barrier to hinder the infiltration of epithelial and connective tissues into defect sites, has been widely used for alveolar bone regeneration, its outcomes remain variable. In this work, a multifunctional nanofibrous hollow microsphere (NFHMS) is developed for enhanced alveolar bone regeneration. The NFHMS is first prepared via combining a double emulsification and a thermally induced phase separation process. Next, E7, a short peptide with high specific affinity to bone marrow-derived stem cells (BMSCs), is conjugated onto the surface of NFHMS. After that, bone forming peptide (BFP), a short peptide derived from bone morphology protein 7 isloaded in calcium phosphate (CaP) nanoparticles, which are further encapsulated in the hollow space of the NFHMS-E7 to form NFHMS-E7-CaP/BFP. The NFHMS-E7-CaP/BFP selectively promoted the adhesion of BMSCs and expelled the adhesion of fibroblasts and epithelial cells. In addition, the BFP is sustainedly released from the NFHMS-E7-CaP/BFP to enhance the osteogenesis of BMSCs. A rat challenging fenestration defect model showed that the NFHMS-E7-CaP/BFP significantly enhanced alveolar bone tissue regeneration. This work provides a novel bioengineering approach for guided bone regeneration.

Apatite-related Na+, Cu2+, Zn2+, CO3 2− containing calcium phosphates nanoparticles: synthesis, characterization and antibacterial properties for medical application

The aim of this study was to prepare and characterize the calcium phosphates modified by different amount of Na+, Cu2+, Zn2+ and CO3 2−, and to investigate their activity in model solution (at pH = 7.45 and 37 °C) and antibacterial properties against Streptococcus pyogenes. According to XRD and FTIR spectroscopy data the apatite-related phases with partial substitution РО4 3− → СО3 2− (B-type) have been prepared. Presence of sodium and carbonate ions led to increase of solubility in model solution during the first 48 h, while modification with both Cu2+ and Zn2+ cations (up to 0.6 wt%) significantly improved antimicrobial properties against Streptococcus pyogenes.

3D printed and smart alginate wound dressings with pH-responsive drug and nanoparticle release

The pH of a wound site can undergo a significant change from its normal range of 5.4–5.6 to a more alkaline environment of 7.2–8.9 after being infected by microorganisms. Therefore, the development of a smart material that can respond to this shift in pH and release antimicrobial agents for effective treatment of wound infections holds great promise for the future of wound care. In the present work, we produced 3D printed alginate wound dressings doped with calcium phosphate nanoparticles (CaP NPs), referred to as alginate-CaP nanocomposites hereafter. The CaP NPs enabled pH-responsive switching of the degradation and drug release of 3D-printed alginate-based wound dressings. Three sizes of rod-shaped CaP NPs were synthesised, including small NPs (62 × 18 nm), medium NPs (197 × 49 nm), and large NPs (496 × 143 nm). The addition of CaP NPs significantly increased both the tensile strength and elongation at the break of the alginate dressings. Additionally, the degradation rate of the alginate-CaP nanocomposite dressings increased with pH, potentiating pH responsive drug delivery from the dressing. Alginate nanocomposites with 1 mg/mL of medium-sized CaP NPs were found to elicit the strongest pH responsiveness. The release rates of rhodamine B, the antibiotic peptide bacitracin, and antimicrobial selenium nanoparticles were assessed, and showed faster release at higher pHs. These results illustrate that CaP NPs can be easily used as a pH-responsive switch to effectively control the degradation and drug release of alginate based wound dressings, enabling increased antimicrobial release at the pH of infected wounds.

Nanotechnology: “Advancing Material Science and Medicine”

Nanotechnology has been a rapidly growing field of advanced science at the inception of this century. Nanotechnology of advanced materials, polymers, principally revolves around endeavours to plan materials at a sub-atomic level to accomplish alluring properties and applications at a naturally visible level. Nanotechnology can be used for the advancement of technologies, ranging from communication and information, health and medicine, future energy, environment and climate change to transport and cultural heritage, personal protective equipment (PPE), fuels, fuel cells, biosensors, disease sensors etc. Nanomaterials will lead to a new approach to manufacturing materials and devices. Faster computers, advanced pharmaceuticals, controlled drug delivery, biocompatible materials, nerve and tissue repair, crackproof surface coatings, better skin care and protection, more efficient catalysts, better and smaller sensors, even more efficient telecommunication. For example, a low risk solution using antibody modified bismuth nanoparticle, in combination with an X-ray dose equivalent to a chest X-ray specifically, has been shown to kill the common bacterium Pseudomonas aeruginosa in a set up designed to resemble a deep wound in human tissue. Nanosized gold particle could catalyse the oxidation of carbon monoxide better than anything previously known. Heparin functionalized nanoparticles have been use for targeted delivery of anti-malarial drugs. Heparin is abundant and cheap, compared to treatments that involve antibodies, an important consideration, since malaria is most common in developing countries. A bone repairing nano-particle paste has been developed that promises faster repair of fractures and breakages. DNA containing two growth genes is encapsulated inside synthetic calcium phosphate nanoparticles. In a remarkable demonstration of the extreme limits of nanoscale engineering, researchers have used the tip of a scanning tunnelling microscope to cleave and form selected chemical bonds in a complex molecule. Many medicinal and industrial endeavours have seen the use of Nanotechnology. Nanoparticles can attach to SARS COV-2 viruses, disrupting their structure and so kill the virus. These and other more recent advances in nanotechnology will be presented at this conference.

Interplay between dental caries pathogens, periodontal pathogens, and sugar molecules: approaches for prevention and treatment.

Globally, oral diseases affect nearly 3.5billion people, accounting for 4.6% of the healthcare expenditure. Common oral diseases include dental caries and periodontal disease, associated with biofilms formed by cariogenic pathogens. Epidemiological studies associate carbohydrates with these diseases due to thesugars metabolized by cariogenic pathogens. This review focuses on dental caries and periodontal pathogens, quorum sensing, lectin-carbohydrate interactions, and various sugar molecules. Cariogenic sugars significantly influence biofilms by enhancing pathogen adhesion, viability, and gene expressions associated with biofilm formation. Moreover, lectin-carbohydrate interactions contribute to biofilm stability. Disrupting these interactions is a potential strategy for oral disease prevention. The use of nanoparticles, such as quantum dots, provides novel insights into lectin-sugar interactions and the development of inhibitors. Additionally, nanomaterials like calcium phosphate nanoparticles neutralize acids and inhibit microbial growth. This overview emphasizes understanding the relationships between oral diseases, microbial communities, and sugars to devise preventive and therapeutic strategies against oral diseases.

A STING agonist-loaded bispecific nanobioconjugate modulates macrophage immune responses to enhance antitumor immunotherapy

Tumor-associated macrophages (TAMs) have become attractive therapeutic targets because of their multifaceted cancer-promoting functions and their abundance in the tumor microenvironment (TME). Here, we construct a stimulator of interferon genes (STING) agonist-loaded bispecific nanobioconjugate for macrophage-mediated cancer immunotherapy. Calcium phosphate (CaP) is used as a carrier to load STING agonist, 2′,5′-3′,5′ cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), to prepare cGAMP-loaded CaP nanoparticles (cGAMP@CaP). Two types of antibodies, anti-CD47 antibody (aCD47) and anti-SIRPα antibody (aSIRPα), are modified on the CaP nanoparticles (cGAMP@CaP@Abs). The resulting STING agonist-loaded bispecific nanobioconjugate not only enhances macrophage phagocytosis through blocking of the CD47-SIRPα axis and the physical bridge of macrophages and tumor cells but also potentiates the activation of the STING pathway by cGAMP in TAMs, accordingly effectively triggering a type I interferon-driven inflammatory program. The nanobioconjugate can target and accumulate at the tumor site, facilitate the infiltration of CD8+ T cells, and reprogram the immunosuppressive tumor microenvironment, achieving remarkable therapeutic efficacy in multiple murine tumor models. Overall, the STING agonist-loaded bispecific nanobioconjugate provides a novel platform for macrophage-mediated tumor immunotherapy.

Magnetic resonance imaging of mesenchymal stem cell – migration towards glioblastoma using a nano-calcium phosphate contrast agent

<img src=” https://s3.amazonaws.com/production.scholastica/article/94159/large/prnano_1162024ga.jpg?1708444945”> Tracking stem cell homing to the brain, their infiltration and brain tissue distribution, are critical for evaluating the efficacy of stem cell-based anti-glioma therapy. Here, we report the use of a biomineral magnetic nano-contrast agent, Fe-doped calcium phosphate nanoparticles (nCP:Fe), to label mesenchymal stem cells (MSCs) and track their migration towards brain tumor using magnetic resonance imaging (MRI). nCP:Fe labelled MSCs implanted intra-ventricularly in a rat C6-glioma model showed longitudinal migration towards tumor-region over 14 days, detected as hypointense signals in T2/T2* weighted-MR images, which was confirmed ex vivo using histological staining. Although, a small fraction of implanted MSCs migrated to the tumor-site, the study demonstrates that, MRI tracking of stem cells using nCP:Fe nano-contrast agent will facilitate better assessment of the efficacy of stem cell-guided anti-tumor therapy.

A curcumin sustained-release hydrogel prepared from Pickering emulsions stabilized by modified amorphous calcium phosphate nanoparticles

A curcumin sustained-release hydrogel prepared from Pickering emulsions stabilized by modified amorphous calcium phosphate nanoparticles

Plaque‐Specific Adhesive Balloons Coated with Calcium Phosphate Nanoparticles Loaded with Rapamycin for Atherosclerosis Therapy

AbstractDrug‐coated balloons (DCBs), serving as a superior alternative to stents, are at the cutting edge of clinical innovations in atherosclerosis management. Nevertheless, the prevalent high flow rates in arterial vascular result in short drug residence times, significantly compromising DCBs’ therapeutic effectiveness. Drawing inspiration from the mechanisms of vascular calcification, a rapamycin‐loaded calcium phosphate nanoparticle (CaP@Rapa) coating for balloons is pioneered. This coating functions as a potent drug anchor in arteries, facilitating the adhesion of rapamycin to plaques and thereby enhancing the local concentration of the rapamycin. To evaluate its therapeutic efficacy in vivo, the rabbit iliac artery atherosclerosis model is innovatively developed, which authentically mirrors the pathological progression of atherosclerosis in humans. The enhanced localized rapamycin retention, along with its pH‐sensitive sustained release characteristics, culminate in substantial reductions in plaque volume, a decrease in intimal hyperplasia, and mitigation of local inflammation in model rabbits. To further substantiate the translational potential of CaP@Rapa balloons, the research on the pig coronary atherosclerosis model is expanded, which yielded results solidifying the clinical promise of CaP@Rapa balloons. In summary, this research not only offers a more effective and reliable alternative to traditional DCB but also paves the way for further clinical trials.

Improved CaP Nanoparticles for Nucleic Acid and Protein Delivery to Neural Primary Cultures and Stem Cells.

Efficiently delivering exogenous materials into primary neurons and neural stem cells (NSCs) has long been a challenge in neurobiology. Existing methods have struggled with complex protocols, unreliable reproducibility, high immunogenicity, and cytotoxicity, causing a huge conundrum and hindering in-depth analyses. Here, we establish a cutting-edge method for transfecting primary neurons and NSCs, named teleofection, by a two-step process to enhance the formation of biocompatible calcium phosphate (CaP) nanoparticles. Teleofection enables both nucleic acid and protein transfection into primary neurons and NSCs, eliminating the need for specialized skills and equipment. It can easily fine-tune transfection efficiency by adjusting the incubation time and nanoparticle quantity, catering to various experimental requirements. Teleofection's versatility allows for the delivery of different cargos into the same cell culture, whether simultaneously or sequentially. This flexibility proves invaluable for long-term studies, enabling the monitoring of neural development and synapse plasticity. Moreover, teleofection ensures the consistent and robust expression of delivered genes, facilitating molecular and biochemical investigations. Teleofection represents a significant advancement in neurobiology, which has promise to transcend the limitations of current gene delivery methods. It offers a user-friendly, cost-effective, and reproducible approach for researchers, potentially revolutionizing our understanding of brain function and development.

Doxycycline-Loaded Calcium Phosphate Nanoparticles with a Pectin Coat Can Ameliorate Lipopolysaccharide-Induced Neuroinflammation Via Enhancing AMPK

Neuroinflammation occurs in response to different injurious triggers to limit their hazardous effects. However, failure to stop this process can end in multiple neurological diseases. Doxycycline (DX) is a tetracycline, with potential antioxidant and anti-inflammatory properties. The current study tested the effects of free DX, DX-loaded calcium phosphate (DX@CaP), and pectin-coated DX@CaP (Pec/DX@CaP) nanoparticles on the lipopolysaccharide (LPS)-induced neuroinflammation in mice and to identify the role of adenosine monophosphate-activated protein kinase (AMPK) in this effect. The present study was conducted on 48 mice, divided into 6 groups, eight mice each. Group 1 (normal control), Group 2 (blank nanoparticles-treated), Group 3 (LPS (untreated)), Groups 4, 5, and 6 received LPS, then Group 4 received free DX, Group 5 received DX-loaded calcium phosphate nanoparticles (DX@CaP), and Group 6 received DX-loaded calcium phosphate nanoparticles with a pectin coat (Pec/DX@CaP). At the end of the experimentation period, behavioral tests were carried out. Then, mice were sacrificed, and brain tissue was extracted and used for histological examination, and assessment of interleukin-6 positive cells in different brain areas, in addition to biochemical measurement of SOD activity, TLR-4, AMPK and Nrf2. LPS can induce prominent neuroinflammation. Treatment with (Pec/DX@CaP) can reverse most behavioral, histopathological, and biochemical changes caused by LPS. The findings of the current study suggest that (Pec/DX@CaP) exerts a significant reverse of LPS-induced neuroinflammation by enhancing SOD activity, AMPK, and Nrf2 expression, in addition to suppression of TLR-4.Graphical

Synergetic effect of essential oils and calcium phosphate nanoparticles for enhancement the corrosion resistance of titanium dental implant.

Calcium phosphate (CaPO4) coating is one of various methods that is used to modify the topography and the chemistry of Ti dental implant surface to solve sever oral problems that result from diseases, accidents, or even caries due to its biocompatibility. In this work, anodized (Ti-bare) was coated by CaPO4 prepared from amorphous calcium phosphate nanoparticles (ACP-NPs) and confirmed the structure by X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FT-IR) techniques. Ti-bare was coated by prepared CaPO4 through the casting process, and the morphology of Ti/CaPO4 was characterized by scanning electron microscope (SEM) where the nano-flakes shape of CaPO4 and measured to be 60 ~ 80 nm was confirmed. The stability of Ti-bare and coated Ti/CaPO4 was studied in a simulated saliva solution using electrochemical impedance spectroscopy (EIS) and linear polarization techniques to deduce their corrosion resistance. Furthermore, three essential oils (EO), Cumin, Thyme, and Coriander, were used to stimulate their synergistic effect with the CaPO4 coat to enhance the corrosion resistance of Ti implant in an oral environment. The fitting EIS parameters based on Rs [RctC]W circuit proved that the charge transfer resistance (Rct) of Ti/CaPO4 increased by 264.4, 88.2, and 437.5% for Cumin, Thyme, and Coriander, respectively, at 2% concentration.

Effects of void defects on the mechanical properties of biphasic calcium phosphate nanoparticles: A molecular dynamics investigation

Porous biphasic calcium phosphate (BCP) ceramics are widely used in bone tissue engineering, and the mechanical properties of BCP implants must be reliable. However, the effects of pore structure (e.g., shape and size) on the mechanical properties are not well understood. In this study, we used molecular dynamics simulations to investigate the influence of pore shape and size on the mechanical behavior of BCP nanoparticles. BCP void models with cylindrical and cuboid pores ranging from 2 to 16 nm in diameter were constructed, and the elastic moduli were calculated. In addition, uniaxial tensile and compressive tests were performed on the models. We found that the pore size had a more significant impact on the mechanical properties of BCP than pore shape. Further, the elastic moduli decreased nonlinearly with increasing pore size. In addition, the tensile and compressive strength also decreased with the increase in pore size, but the ductility improved. Furthermore, deformation and fracture were more likely to occur near the pores and at the phase interfaces as a result of high atomic local strain in the calcium-deficient hydroxyapatite area. The results of this work reveal the effects of pore parameters on the mechanical properties of porous BCP at the nanometer level, which may aid the design of improved porous and multiphase CaP-based biomaterials for bone regeneration.

Tailoring the structure and self-activated photoluminescence of carbonated amorphous calcium phosphate nanoparticles for bioimaging applications.

Self-activated luminescent calcium phosphate (CaP) nanoparticles, including hydroxyapatite (HA) and amorphous calcium phosphate (ACP), are promising for bioimaging and theragnostic applications in nanomedicine, eliminating the need for activator ions or fluorophores. In this study, we developed luminescent and stable citrate-functionalized carbonated ACP nanoparticles for bioimaging purposes. Our findings revealed that both the CO32- content and the posterior heating step at 400 °C significantly influenced the composition and the structural ordering of the chemically precipitated ACP nanoparticles, impacting the intensity, broadness, and position of the defect-related photoluminescence (PL) emission band. The heat-treated samples also exhibited excitation-dependent PL under excitation wavelengths typically used in bioimaging (λexc = 405, 488, 561, and 640 nm). Citrate functionalization improved the PL intensity of the nanoparticles by inhibiting non-radiative deactivation mechanisms in solution. Additionally, it resulted in an increased colloidal stability and reduced aggregation, high stability of the metastable amorphous phase and the PL emission for at least 96 h in water and supplemented culture medium. MTT assay of HepaRG cells, incubated for 24 and 48 h with the nanoparticles in concentrations ranging from 10 to 320 μg mL-1, evidenced their high biocompatibility. Internalization studies using the nanoparticles self-activated luminescence showed that cellular uptake of the nanoparticles is both time (4-24 h) and concentration (160-320 μg mL-1) dependent. Experiments using confocal laser scanning microscopy allowed the successful imaging of the nanoparticles inside cells via their intrinsic PL after 4 h of incubation. Our results highlight the potential use of citrate-functionalized carbonated ACP nanoparticles for use in internalization assays and bioimaging procedures.

Nano iron doped calcium phosphates act as pH-Sensitive and biodegradable peroxidase-like nanozymes for cancer chemodynamic therapy and MRI contrast

All types of cancer are a threat to human health and among the current therapies, the highly invasive chemotherapy is still the standard in several cases. Currently, more specific and less invasive therapies are being developed and chemodynamic therapy arose as a viable alternative. This strategy takes advantage of the tumour biochemical characteristics such as the acidic pH (∼6.0) and the high concentration of H2O2 (∼50 μM–∼1 mM). In these specific conditions, nanoparticles with peroxidase-like catalytic properties can convert H2O2 into highly toxic reactive oxygen species that induce oxidative stress in cancer cells. One of the remarkable advantages of chemodynamic therapy concerns the peroxidase-like activity, which only occurs in specific pH environments, as found in the tumour microenvironment. At the same time, the produced reactive oxygen species are short-lived, meaning that they will not travel outside the tumoral region, thus not affecting healthy surrounding tissues.This work reports on the production and characterization of iron doped calcium phosphate nanoparticles, as a fully biodegradable alternative to existing chemodynamic agents. By incorporating iron in different oxidation states into the lattice through calcium substitution, these nanoparticles exhibit high catalytic conversion of H2O2 into reactive oxygen species, more specifically into the hydroxyl radical, independently of the iron oxidation state. Outstanding results concern the significant toxicity, only obtained at pH 6.0 and in the presence of H2O2, while remaining non-toxic in physiological conditions (pH7.4) when tested against triple negative breast cancer cells, thus proving the specificity of the treatment in tumoral conditions. Moreover, the presented magnetic properties allowed them to produce significant contrast in magnetic resonance imaging, with different results depending on the iron oxidation state.

Lung-to-Heart Nano-in-Micro Peptide Promotes Cardiac Recovery in a Pig Model of Chronic Heart Failure

BackgroundThe lack of disease-modifying drugs is one of the major unmet needs in patients with heart failure (HF). Peptides are highly selective molecules with the potential to act directly on cardiomyocytes. However, a strategy for effective delivery of therapeutics to the heart is lacking. ObjectivesIn this study, the authors sought to assess tolerability and efficacy of an inhalable lung-to-heart nano-in-micro technology (LungToHeartNIM) for cardiac-specific targeting of a mimetic peptide (MP), a first-in-class for modulating impaired L-type calcium channel (LTCC) trafficking, in a clinically relevant porcine model of HF. MethodsHeart failure with reduced ejection fraction (HFrEF) was induced in Göttingen minipigs by means of tachypacing over 6 weeks. In a setting of overt HFrEF (left ventricular ejection fraction [LVEF] 30% ± 8%), animals were randomized and treatment was started after 4 weeks of tachypacing. HFrEF animals inhaled either a dry powder composed of mannitol-based microparticles embedding biocompatible MP-loaded calcium phosphate nanoparticles (dpCaP-MP) or the LungToHeartNIM only (dpCaP without MP). Efficacy was evaluated with the use of echocardiography, invasive hemodynamics, and biomarker assessment. ResultsDpCaP-MP inhalation restored systolic function, as shown by an absolute LVEF increase over the treatment period of 17% ± 6%, while reversing cardiac remodeling and reducing pulmonary congestion. The effect was recapitulated ex vivo in cardiac myofibrils from treated HF animals. The treatment was well tolerated, and no adverse events occurred. ConclusionsThe overall tolerability of LungToHeartNIM along with the beneficial effects of the LTCC modulator point toward a game-changing treatment for HFrEF patients, also demonstrating the effective delivery of a therapeutic peptide to the diseased heart.

Dexamethasone-Loaded Lipid Calcium Phosphate Nanoparticles Treat Experimental Colitis by Regulating Macrophage Polarization in Inflammatory Sites.

The M1/M2 polarization of intestinal macrophages exerts an essential function in the pathogenesis of ulcerative colitis (UC), which can be adjusted to alleviate the UC symptoms. A kind of pH-sensitive lipid calcium phosphate core-shell nanoparticles (NPs), co-loading with dexamethasone (Dex) and its water-soluble salts, dexamethasone sodium phosphate (Dsp), was constructed to comprehensively regulate macrophages in different states towards the M2 phenotype to promote anti-inflammatory effects. Dex and Dsp were loaded in the outer lipid shell and inner lipid calcium phosphate (Cap) core of the LdCaPd NPs, respectively. Then, the morphology of NPs and methods for determining drug concentration were investigated, followed by in vitro protein adsorption, stability, and release tests. Cell experiments evaluated the cytotoxicity, cellular uptake, and macrophage polarization induction ability of NPs. The in vivo distribution and anti-inflammatory effect of NPs were evaluated through a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced BALB/c mice ulcerative colitis model. The LdCaPd NPs showed a particle size of about 200 nm and achieved considerable loading amounts of Dex and Dsp. The in vitro and in vivo studies revealed that in the acidic UC microenvironment, the cationic lipid shell of LdCaPd underwent protonated dissociation to release Dex first for creating a microenvironment conducive to M2 polarization. Then, the exposed CaP core was further engulfed by M1 macrophages to release Dsp to restrict the pro-inflammatory cytokines production by inhibiting the activation and function of the nuclear factor kappa-B (NF-κB) through activating the GC receptor and the NF kappa B inhibitor α (I-κBα), respectively, ultimately reversing the M1 polarization to promote the anti-inflammatory therapy. The LdCaPd NPs accomplished the sequential release of Dex and Dsp to the UC site and the inflammatory M1 macrophages at this site, promoting the regulation of macrophage polarization to accelerate the remission of UC symptoms.

A nano-bioconjugate modified with anti-SIRPα antibodies and antisense oligonucleotides of mTOR for anti-atherosclerosis therapy

Atherosclerosis is the main cause of a series of fatal cardiovascular diseases, characterized by pathological accumulation of apoptotic cells and lipids. Pro-phagocytic antibody-based or pro-autophagy gene-based therapies are currently being explored to stimulate the phagocytic clearance of apoptotic cells and lipid metabolism; however, monotherapies are only moderately effective or require high doses with unacceptable side effects. Herein, we engineered a specific nano-bioconjugate loaded with antisense oligonucleotides (ASOs) of mammalian target of rapamycin (mTOR) and modified with anti-signal-regulated protein-α antibody (aSIRPα) for macrophage-mediated atherosclerosis therapy. The specific nano-bioconjugate utilized acid-responsive calcium phosphate (CaP) as a carrier to load mTOR ASOs, coated with lipid on the surface of CaP nanoparticles (ASOs@CaP), and subsequently modified with aSIRPα. The resulting nano-bioconjugates could accumulate within atherosclerotic plaques, target to macrophages and reactivate lesional phagocytosis through blocking the CD47-SIRPα signaling axis. In addition, efficient delivery of mTOR ASOs inhibited mTOR expression, which significantly restored impaired autophagy. The combined action of mTOR ASOs and aSIRPα reduced apoptotic cells and lipids accumulation. This nanotherapy significantly reduced plaque burden and inhibited progression of atherosclerotic lesions. These results show the potential of specific nano-bioconjugates for the prevention of atherosclerotic cardiovascular disease. Statement of significanceAtherosclerosis is the main cause of a series of fatal cardiovascular diseases. Pro-phagocytic antibody-based or pro-autophagy gene-based therapies are currently being explored to stimulate the phagocytic clearance of apoptotic cells and lipid metabolism; however, monotherapies are only moderately effective or require high doses with unacceptable side effects. Herein, we engineered a specific nano-bioconjugate loaded with antisense oligonucleotides (ASOs) of mammalian target of rapamycin (mTOR) and modified with anti-signal-regulated protein-α antibody (aSIRPα) for macrophage-mediated atherosclerosis therapy. Our study demonstrated that the combined action of mTOR ASOs and aSIRPα reduced apoptotic cells and lipids accumulation. This nanotherapy significantly reduced plaque burden and inhibited progression of atherosclerotic lesions. These results show the potential of specific nano-bioconjugates for the prevention of atherosclerotic cardiovascular disease.

Assessment of Anti-Carcinogenic Potential of Neem (<i>Azadirachta indica</i>) Leaf Extract Loaded Calcium Phosphate Nanoparticles against Experimentally Induced Mammary Carcinogenesis in Rats

Considering the need for alternative medicine in alleviation of tumors and use of nanotechnology in furthering the action of herbal/natural products, the present study was designed to evaluate the anti-carcinogenic potential of Neem leaf Extract (NE) loaded calcium phosphate nanoparticles (NE-CaNP) on 7, 12-Dimethylbenzanthracene (DMBA) induced mammary tumors in female Sprague-Dawley rats. Ultrastructurally, the NE-CaNP were smooth, spherical with a tendency to agglomerate and evenly distributed. The NE-CaNP had a mean diameter of 231.4 ± 89.2 nm and zeta potential of -31.3mV. The mean coupling efficiency of CaNP was 90-91 %. The experimental trial consisted of control, NE-CaNP control, DMBA, DMBA+NE and DMBA+NE-CaNP groups. The mean latency periods for occurrence of mammary tumor were significantly (P ≤ 0.05) increased in the DMBA+NE and DMBA+NE-CaNP groups compared to the DMBA group. The mean latency period in the DMBA+NE-CaNP group was significantly (P ≤ 0.05) higher than the DMBA+NE group. The mean tumor frequency, volume and weight were significantly (P ≤ 0.05) decreased in the DMBA+NE-CaNP group. Histopathologically, the number of benign lesions was found highest (47.54%) in DMBA+NE-CaNP group rats. The relative percent reduction in malignancy as compared to the DMBA group was 42.86% and 54.29% in the DMBA+NE and DMBA+NE-CaNP groups respectively. In conclusion, the neem leaf extract loaded calcium phosphate nanoparticles were found to have better anti-carcinogenic potential by significantly reducing the incidence, frequency, weight, volume, malignancy and increased the tumor latency period of DMBA induced mammary tumors in female Sprague-Dawley rats as compared to rats treated with neem extract alone. Findings of the present study suggested that the neem leaf extract loaded calcium phosphate nanoparticles (NE-CaNP) has immense anticancer potential in terms of reduction in tumor burden and malignancy.