RESUMEN

The current opioid epidemic is one of the most profound public health crises facing the United States. Despite that it has been under the spotlight for years, available treatments for opioid use disorder (OUD) and overdose are limited to opioid receptor ligands such as the agonist methadone and the overdose reversing drugs such as naloxone. Vaccines are emerging as an alternative strategy to combat OUD and prevent relapse and overdose. Most vaccine candidates consist of a conjugate structure containing the target opioid attached to an immunogenic carrier protein. However, conjugate vaccines have demonstrated some intrinsic shortfalls, such as fast degradation and poor recognition by immune cells. To overcome these challenges, we proposed a lipid-PLGA hybrid nanoparticle (hNP)-based vaccine against oxycodone (OXY), which is one of the most frequently misused opioid analgesics. The hNP-based OXY vaccine exhibited superior immunogenicity and pharmacokinetic efficacy in comparison to its conjugate vaccine counterpart. Specifically, the hNP-based OXY vaccine formulated with subunit keyhole limpet hemocyanin (sKLH) as the carrier protein and aluminum hydroxide (Alum) as the adjuvant (OXY-sKLH-hNP(Alum)) elicited the most potent OXY-specific antibody response in mice. The induced antibodies efficiently bound with OXY molecules in blood and suppressed their entry into the brain. In a following dose-response study, OXY-sKLH-hNP(Alum) equivalent to 60 µg of sKLH was determined to be the most promising OXY vaccine candidate moving forward. This study provides evidence that hybrid nanoparticle-based vaccines may be superior vaccine candidates than conjugate vaccines and will be beneficial in treating those suffering from OUD.

Asunto(s)

Nanopartículas , Oxicodona , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Animales , Oxicodona/farmacocinética , Oxicodona/inmunología , Oxicodona/administración & dosificación , Oxicodona/química , Nanopartículas/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Lípidos/química , Ratones , Femenino , Vacunas/farmacocinética , Vacunas/inmunología , Vacunas/administración & dosificación , Ratones Endogámicos BALB C

RESUMEN

Introduction: RNA interference (RNAi) stands as a widely employed gene interference technology, with small interfering RNA (siRNA) emerging as a promising tool for cancer treatment. However, the inherent limitations of siRNA, such as easy degradation and low bioavailability, hamper its efficacy in cancer therapy. To address these challenges, this study focused on the development of a nanocarrier system (HLM-N@DOX/R) capable of delivering both siRNA and doxorubicin for the treatment of breast cancer. Methods: The study involved a comprehensive investigation into various characteristics of the nanocarrier, including shape, diameter, Fourier transform infrared (FT-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS), encapsulation efficiency, and drug loading. Subsequently, in vitro and in vivo studies were conducted on cytotoxicity, cellular uptake, cellular immunofluorescence, lysosome escape, and mouse tumor models to evaluate the efficacy of the nanocarrier in reversing tumor multidrug resistance and anti-tumor effects. Results: The results showed that HLM-N@DOX/R had a high encapsulation efficiency and drug loading capacity, and exhibited pH/redox dual responsive drug release characteristics. In vitro and in vivo studies showed that HLM-N@DOX/R inhibited the expression of P-gp by 80%, inhibited MDR tumor growth by 71% and eliminated P protein mediated multidrug resistance. Conclusion: In summary, HLM-N holds tremendous potential as an effective and targeted co-delivery system for DOX and P-gp siRNA, offering a promising strategy for overcoming MDR in breast cancer.

Asunto(s)

Neoplasias de la Mama , Doxorrubicina , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Liposomas , ARN Interferente Pequeño , Animales , Doxorrubicina/farmacología , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/administración & dosificación , Femenino , Liposomas/química , Ratones , Resistencia a Antineoplásicos/efectos de los fármacos , Humanos , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/química , ARN Interferente Pequeño/farmacocinética , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Células MCF-7 , Ratones Endogámicos BALB C , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Nanopartículas/química , Liberación de Fármacos , Antibióticos Antineoplásicos/farmacología , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/farmacocinética , Ensayos Antitumor por Modelo de Xenoinjerto

RESUMEN

Antigen delivery via respiratory mucosal surfaces is an interesting needle-free option for vaccination. Nonetheless, it demands for the design of especially tailored formulations. Here, lipid/poly(lactic-co-glycolic) acid (PLGA) hybrid nanoparticles (hNPs) for the combined delivery of an antigen, ovalbumin (Ova), and an adjuvant, synthetic unmethylated cytosine-phosphate-guanine oligodeoxynucleotide (CpG) motifs, is developed. A panel of Ova/CpG-loaded lipid@PLGA hNPs with tunable size and surface is attained by exploiting two lipid moieties, 1,2 distearoil-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol) (DSPE-PEG) and monophosphoryl lipid A (MPLA), with or without polyethyleneimine (PEI). It is gained insights on the lipid@PLGA hNPs through a combination of techniques to analytically determine the specific moiety on the surface, the spatial distribution of the components and the internal structure of the nanoplatforms. The collected results suggest that PEI plays a role of paramount importance not only in promoting in vitro antigen escape from lysosomes and enhancing antigen cross-presentation, but also in determining the arrangement of the moieties in the final architecture of the hNPs. Though multicomponent PEI-engineered lipid@PLGA hNPs turn out as a viable strategy for delivery of antigens and adjuvant to the respiratory mucosa, tunable nanoparticle features are achievable only through the optimal selection of the components and their relative amounts.

RESUMEN

In the present work, a simple intelligence-based computation of artificial neural networks with the Levenberg-Marquardt backpropagation algorithm is developed to analyze the new ferromagnetic hybrid nanofluid flow model in the presence of a magnetic dipole within the context of flow over a stretching sheet. A combination of cobalt and iron (III) oxide (Co-Fe2O3) is strategically selected as ferromagnetic hybrid nanoparticles within the base fluid, water. The initial representation of the developed ferromagnetic hybrid nanofluid flow model, which is a system of highly nonlinear partial differential equations, is transformed into a system of nonlinear ordinary differential equations using appropriate similarity transformations. The reference data set of the possible outcomes is obtained from bvp4c for varying the parameters of the ferromagnetic hybrid nanofluid flow model. The estimated solutions of the proposed model are described during the testing, training, and validation phases of the backpropagated neural network. The performance evaluation and comparative study of the algorithm are carried out by regression analysis, error histograms, function fitting graphs, and mean squared error results. The findings of our study analyze the increasing effect of the ferrohydrodynamic interaction parameter ß to enhance the temperature and velocity profiles, while increasing the thermal relaxation parameter α decreases the temperature profile. The performance on MSE was shown for the temperature and velocity profiles of the developed model about 9.1703e-10, 7.1313ee-10, 3.1462e-10, and 4.8747e-10. The accuracy of the artificial neural networks with the Levenberg-Marquardt algorithm method is confirmed through various analyses and comparative results with the reference data. The purpose of this study is to enhance understanding of ferromagnetic hybrid nanofluid flow models using artificial neural networks with the Levenberg-Marquardt algorithm, offering precise analysis of key parameter effects on temperature and velocity profiles. Future studies will provide novel soft computing methods that leverage artificial neural networks to effectively solve problems in fluid mechanics and expand to engineering applications, improving their usefulness in tackling real-world problems.

RESUMEN

Exosome-nanoparticle hybrid nanoplatforms, can be prepared by combining exosomes with different types of nanoparticles. The main purpose of combining exosomes with nanoparticles is to overcome the limitations of using each of them as drug delivery systems. Using nanoparticles for drug delivery has some limitations, such as high immunogenicity, poor cellular uptake, low biocompatibility, cytotoxicity, low stability, and rapid clearance by immune cells. However, using exosomes as drug delivery systems also has its own drawbacks, such as poor encapsulation efficiency, low production yield, and the inability to load large molecules. These limitations can be addressed by utilizing hybrid nanoplatforms. Additionally, the use of exosomes allows for targeted delivery within the hybrid system. Exosome-inorganic/organic hybrid nanoparticles may be used for both therapy and diagnosis in the future. This may lead to the development of personalized medicine using hybrid nanoparticles. However, there are a few challenges associated with this. Surface modifications, adding functional groups, surface charge adjustments, and preparing nanoparticles with the desired size are crucial to the possibility of preparing exosome-nanoparticle hybrids. Additional challenges for the successful implementation of hybrid platforms in medical treatments and diagnostics include scaling up the manufacturing process and ensuring consistent quality and reproducibility across various batches. This review focuses on various types of exosome-nanoparticle hybrid systems and also discusses the preparation and loading methods for these hybrid nanoplatforms. Furthermore, the potential applications of these hybrid nanocarriers in drug/gene delivery, disease treatment and diagnosis, and cell/tissue imaging are explained.

Asunto(s)

Exosomas , Nanopartículas , Exosomas/metabolismo , Humanos , Animales , Nanopartículas/química , Sistemas de Liberación de Medicamentos/métodos

RESUMEN

Lung cancer is a leading cause of global cancer mortality, often treated with chemotherapeutic agents. However, conventional approaches such as oral or intravenous administration of drugs yield low bioavailability and adverse effects. Nanotechnology has unlocked new gateways for delivering medicine to their target sites. Lipid-polymer hybrid nanoparticles (LPHNPs) are one of the nano-scaled delivery platforms that have been studied to exploit advantages of liposomes and polymers, enhancing stability, drug loading, biocompatibility and controlled release. Pulmonary administration of drug-loaded LPHNPs enables direct lung deposition, rapid onset of action and heightened efficacy at low doses of drugs. In this manuscript, we will review the potential of LPHNPs in management of lung cancer through pulmonary administration.

---

[Box: see text].

RESUMEN

Anthracycline-based therapies exert endothelial damages through peroxidation and the production of proinflammatory cytokines, resulting in a high risk of cardiovascular complications in cancer patients. Hyaluronic acid-based hybrid nanoparticles (LicpHA) are effective pharmacological tools that can target endothelial cells and deliver drugs or nutraceuticals. This study aimed to prepared and characterized a novel LicpHA loaded with Rutin (LicpHA Rutin), a flavonoid with high antioxidant and anti-inflammatory properties, to protect endothelial cells against epirubicin-mediated endothelial damages. LicpHA Rutin was prepared using phosphatidylcholine, cholesterol, poloxamers, and hyaluronic acid by a modified nanoprecipitation technique. The chemical-physical characterization of the nanoparticles was carried out (size, zeta potential, morphology, stability, thermal analysis, and encapsulation efficiency). Cytotoxicity studies were performed in human endothelial cells exposed to epirubicin alone or in combination with Free-Rutin or LicpHA Rutin. Anti-inflammatory studies were performed through the intracellular quantification of NLRP-3, MyD-88, IL-1ß, IL-6, IL17-α, TNF-α, IL-10, and IL-4 using selective ELISA methods. Morphological studies via TEM and image analysis highlighted a heterogeneous population of LicpHA particles with non-spherical shapes (circularity equal to 0.78 ± 0.14), and the particle size was slightly affected by Rutin entrapment (the mean diameter varied from 179 ± 4 nm to 209 ± 4 nm). Thermal analysis and zeta potential analyses confirmed the influence of Rutin on the chemical-physical properties of LicpHA Rutin, mainly indicated by the decrease in the surface negative charge (from -35 ± 1 mV to -30 ± 0.5 mV). Cellular studies demonstrated that LicpHA Rutin significantly reduced cell death and inflammation when compared to epirubicin alone. The levels of intracellular NLRP3, Myd-88, and proinflammatory cytokines were significantly lower in epirubicin + LicpHA Rutin-exposed cells when compared to epirubicin groups (p < 0.001). Hyaluronic acid-based nanoparticles loaded with Rutin exerts significant vasculo-protective properties during exposure to anthracyclines. The overall picture of this study pushes towards preclinical and clinical studies in models of anthracycline-induced vascular damages.

RESUMEN

Ivermectin (IVM), a drug originally used for treating parasitic infections, is being explored for its potential applications in cancer therapy. Despite the promising anti-cancer effects of IVM, its low water solubility limits its bioavailability and, consequently, its biological efficacy as an oral formulation. To overcome this challenge, our research focused on developing IVM-loaded lipid polymer hybrid nanoparticles (LPHNPs) designed for potential pulmonary administration. IVM-loaded LPHNPs were developed using the emulsion solvent evaporation method and characterized in terms of particle size, morphology, entrapment efficiency, and release pattern. Solid phase characterization was investigated by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). Using a Twin stage impinger (TSI) attached to a device, aerosolization properties of the developed LPHNPs were studied at a flow rate of 60 L/min, and IVM was determined by a validated HPLC method. IVM-loaded LPHNPs demonstrated spherical-shaped particles between 302 and 350 nm. Developed formulations showed an entrapment efficiency between 68 and 80% and a sustained 50 to 60% IVM release pattern within 96 h. Carr's index (CI), Hausner ratio (HR), and angle of repose (θ) indicated proper flowability of the fabricated LPHNPs. The in vitro aerosolization analysis revealed fine particle fractions (FPFs) ranging from 18.53% to 24.77%. This in vitro study demonstrates the potential of IVM-loaded LPHNPs as a delivery vehicle through the pulmonary route.

RESUMEN

Oral administration of BCS class IV anticancer agents has always remained challenging and frequently results in poor oral bioavailability. The goal of the current study was to develop hybrid nanoparticles (HNPs) employing cholesterol and poloxamer-407 to boost paclitaxel's (PTX) oral bioavailability. A series of HNPs with different cholesterol and poloxamer-407 ratios were developed utilizing a single-step nanoprecipitation technique. The PTX loaded HNPs were characterized systematically via particle size, zeta potential, polydispersity index, surface morphology, in vitro drug release, FTIR, DSC, XRD, acute oral toxicity analysis, hemolysis evaluation, accelerated stability studies, and in vivo pharmacokinetic analysis. The HNPs were found within the range of 106.6±55.60 - 244.5±88.24 nm diameter with the polydispersity index ranging from 0.20±0.03 - 0.51±0.11. SEM confirmed circular, nonporous, and smooth surfaces of HNPs. PTX loaded HNPs exhibited controlled release profile. The compatibility between the components of formulation, thermal stability, and amorphous nature of HNPs were confirmed by FTIR, DSC, and XRD, respectively. Acute oral toxicity analysis revealed that developed system have no deleterious effects on the animals' cellular structures. HNPs demonstrated notable cytotoxic effects and were hemocompatible at relatively higher concentrations. In vivo pharmacokinetic profile (AUC0-∞, AUMC0-∞, t1/2, and MRT0-∞) of the PTX loaded HNPs was improved as compared to pure PTX. It is concluded from our findings that the developed HNPs are hemocompatible, biocompatible and have significantly enhanced the oral bioavailability of PTX.

Asunto(s)

Disponibilidad Biológica , Portadores de Fármacos , Nanopartículas , Paclitaxel , Paclitaxel/farmacocinética , Paclitaxel/administración & dosificación , Paclitaxel/química , Paclitaxel/farmacología , Animales , Administración Oral , Portadores de Fármacos/química , Nanopartículas/química , Materiales Biocompatibles/química , Ratas , Tamaño de la Partícula , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/farmacocinética , Antineoplásicos Fitogénicos/farmacología , Masculino , Poloxámero/química , Hemólisis/efectos de los fármacos , Liberación de Fármacos , Colesterol/química

RESUMEN

Solasonine (SS) and solamargine (SM) are alkaloids known for their antioxidant and anticancer properties, which can be further enhanced by encapsulating them in nanoparticles. This led to a study on the potential therapeutic benefits of SS and SM against bladder cancer when encapsulated in lipid-polymer hybrid nanoparticles (LPHNP). The LPHNP loaded with SS/SM were prepared using the emulsion and sonication method and their physical-chemical properties characterized. The biological effects of these nanoparticles were then tested in both 2D and 3D bladder cancer cell culture models, as well as in a syngeneic orthotopic mouse model based on the MB49 cell line and ethanol epithelial injury. The LPHNP-SS/SM had an average size of 130 nm, a polydispersity index of 0.22 and a positive zeta potential, indicating the presence of chitosan coating on the nanoparticle surface. The dispersion of LPHNP-SS/SM was found to be monodispersed with a span index of 0.539, as measured by nanoparticle tracking analysis (NTA). The recrystallization index, calculated from DSC data, was higher for the LPHNP-SS/SM compared to LPHNPs alone, confirming the presence of alkaloids within the lipid matrix. The encapsulation efficiency (EE%) was also high, with 91.08 % for SS and 88.35 % for SM. Morphological analysis by AFM and Cryo-TEM revealed that the nanoparticles had a spherical shape and core-shell structure. The study showed that the LPHNP-SS/SM exhibited mucoadhesive properties by physically interacting with mucin, suggesting a potential improvement in interaction with mucous membrane. Both the free and nanoencapsulated SS/SM demonstrated dose-dependent cytotoxicity against bladder cancer cell lines after 24 and 72 h of treatment. In 3D bladder cell culture, the nanoencapsulated SS/SM showed an IC50 two-fold lower than free SS/SM. In vivo studies, the LPHNP-SS/SM displayed an antitumoral effect at high doses, leading to a significant reduction in bladder volume compared to the positive control. However, there were observed instances of systemic toxicity and liver damage, indicated by elevated levels of transaminases (TGO and TGP). Overall, these results indicate that the LPHNPs effectively encapsulated SS/SM, showing high encapsulation efficiency and stability, along with promising in vitro and in vivo antitumoral effects against bladder cancer. Further evaluation of its systemic toxicity effects is necessary to ensure its safety and efficacy for potential clinical application.

Asunto(s)

Lípidos , Nanopartículas , Alcaloides Solanáceos , Neoplasias de la Vejiga Urinaria , Animales , Nanopartículas/química , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Línea Celular Tumoral , Lípidos/química , Alcaloides Solanáceos/administración & dosificación , Alcaloides Solanáceos/química , Alcaloides Solanáceos/farmacología , Polímeros/química , Ratones , Humanos , Femenino , Portadores de Fármacos/química , Antineoplásicos/química , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Tamaño de la Partícula , Supervivencia Celular/efectos de los fármacos , Ratones Endogámicos C57BL

Asunto(s)

Lípidos , Nanopartículas , Patentes como Asunto , Polímeros , Nanopartículas/química , Polímeros/química , Lípidos/química , Humanos , Portadores de Fármacos/química

RESUMEN

Overexpression of permeability-glycoprotein (P-gp) transporter leads to multidrug resistance (MDR) through cellular exclusion of chemotherapeutics. Co-administration of P-gp inhibitors and chemotherapeutics is a promising approach for improving the efficacy of therapy. Nevertheless, problems in pharmacokinetics, toxicity and solubility limit the application of P-gp inhibitors. Herein, we developed a novel all-in-one hybrid nanoparticle system to overcome MDR in doxorubicin (DOX)-resistant breast cancer. First, folic acid-modified DOX-loaded mesoporous silica nanoparticles (MSNs) were prepared and then loaded into PEGylated poly(lactic-co-glycolic acid) (PLGA) nanoparticles along with a P-gp inhibitor, elacridar. This hybrid nanoparticle system had high drug loading capacity, enabled both passive and active targeting of tumour tissues, and exhibited sequential and pH-triggered release of drugs. In vitro and in vivo studies in DOX-resistant breast cancer demonstrated the ability of the hybrid nanoparticles to reverse P-gp-mediated drug resistance. The nanoparticles were efficiently taken up by the breast cancer cells and delivered elacridar, in vitro. Biodistribution studies demonstrated substantial accumulation of the folate receptor-targeted PLGA/MSN hybrid nanoparticles in tumour-bearing mice. Moreover, deceleration of the tumour growth was remarkable in the animals administered with the DOX and elacridar co-loaded hybrid nanoparticles when compared to those treated with the marketed liposomal DOX (Caelyx®) or its combination with elacridar.

RESUMEN

In this study, for enhancing the resistance of probiotics to environmental factors, we designed a microgel beads delivery system loaded with synbiotics. Multiple droplets of W1/O/W2 emulsions stabilized with zein-apple pectin hybrid nanoparticles (ZAHPs) acted as the inner "egg," whereas a three-dimensional network of poly-L-lysine (PLL)-alginate-CaCl2 (Ca) crosslinked gel layers served as the outermost "box." ZAHPs with a mass ratio of 2:1 zein-to-apple pectin showed excellent wettability (three-phase contact angle = 89.88°). The results of the ζ-potentials and Fourier transform infrared spectroscopy demonstrate that electrostatic interaction forces and hydrogen bonding were the main forces involved in the formation of ZAHPs. On this basis, we prepared W1/O/W2 emulsions with other preparation parameters and observed their microstructures by optical microscopy and confocal laser scanning microscope. The multi-chambered structures of W1/O/W2 emulsions were successfully visualized. Finally, the W1/O/W2 emulsions were coated with PLL-alginate-Ca using the solution extrusion method. The results of the in vitro colonic digestion stage reveal that the survival rate of probiotics in the microgel beads was about 75.11%, which was significantly higher than that of the free. Moreover, probiotics encapsulated in microgel beads also showed positive storage stability. Apple pectin would serve as both an emulsifier and a prebiotic. Thus, the results indicate that the "egg-box" shaped microgel beads, designed on the basis of pH-sensitive and enzyme-triggered mechanisms, can enhance the efficiency of probiotics translocation in the digestive tract and mediate spatiotemporal controlled release.

RESUMEN

Despite the promising potential of Solanum plant glycoalkaloids in combating skin cancer, their clinical trials have been halted due to dose-dependent toxicity and poor water solubility. In this study, we present a rational approach to address these limitations and ensure colloidal stability of the nanoformulation over time by designing solid lipid-polymer hybrid nanoparticles (SLPH). Leveraging the biocompatible and cationic properties of polyaspartamides, we employed a new polyaspartamide derivative (P1) as a raw material for this class of nanostructures. Subsequently, we prepared SLPH through a one-step process involving hot-melt emulsification followed by ultrasonication. The physicochemical properties of the SLPH were thoroughly characterized using dynamic light scattering (DLS), ζ-potential analysis, nanoparticle tracking analysis (NTA), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), and transmission electron microscopy (TEM). The optimized formulation exhibited long-term stability over six months under low temperatures, maintaining a particle size around 200 nm, a polydispersity index (PdI) lower than 0.2, and a ζ-potential between +35-40 mV. Furthermore, we evaluated the cytotoxic effect of the SLPH against human cutaneous melanoma cells (SK-MEL-28) compared to human foreskin fibroblast cells (HFF-1). Encapsulation of glycoalkaloids into the nanoparticles (SLPH-GE) resulted in a two-fold greater selective cytotoxic profile for melanoma cells than glycoalkaloids-free (GE). The nanoparticles disrupted the stratum corneum barrier with a penetration depth of approximately 77 µm. These findings underscore the potential of the developed nanosystem as an effective glycoalkaloid carrier with suitable colloidal and biological properties for further studies in topical treatment strategies for cutaneous melanoma.

Asunto(s)

Lípidos , Melanoma , Nanopartículas , Polímeros , Humanos , Nanopartículas/química , Lípidos/química , Melanoma/tratamiento farmacológico , Melanoma/patología , Polímeros/química , Polímeros/farmacología , Supervivencia Celular/efectos de los fármacos , Portadores de Fármacos/química , Tamaño de la Partícula , Alcaloides/química , Alcaloides/farmacología , Línea Celular Tumoral , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Antineoplásicos/farmacología , Antineoplásicos/química , Administración Tópica , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Propiedades de Superficie

RESUMEN

Methanol is not only a promising liquid hydrogen carrier but also an important feedstock chemical for chemical synthesis. Catalyst design is vital for enabling the reactions to occur under ambient conditions. This study reports a new class of van der Waals heterojunction photocatalyst, which is synthesized by hot-injection method, whereby carbon dots (CDs) are grown in situ on ZnSe nanoplatelets (NPLs), i.e., metal chalcogenide quantum wells. The resultant organic-inorganic hybrid nanoparticles, CD-NPLs, are able to perform methanol dehydrogenation through CH splitting. The heterostructure has enabled light-induced charge transfer from the CDs into the NPLs occurring on a sub-nanosecond timescale, with charges remaining separated across the CD-NPLs heterostructure for longer than 500 ns. This resulted in significantly heightened H2 production rate of 107 µmole·g-1·h-1 and enhanced photocurrent density up to 34 µA cm-2 at 1 V bias potential. EPR and NMR analyses confirmed the occurrence of α-CH splitting and CC coupling. The novel CD-based organic-inorganic semiconductor heterojunction is poised to enable the discovery of a host of new nano-hybrid photocatalysts with full tunability in the band structure, charge transfer, and divergent surface chemistry for guiding photoredox pathways and accelerating reaction rates.

RESUMEN

Theranostics, a method that combines targeted therapy and diagnostic imaging, has emerged as a viable route for enhancing cancer treatment, and hybrid nanoparticles (HNPs) are at the forefront of this field. Metallic, polymeric, lipid-based, and silica- based HNPs are studied for targeting and biocompatibility. Using HNPs, chemotherapeutic drugs, small interfering RNA, and therapeutic genes can be given precisely and controlled. This enhances therapeutic efficacy and reduces adverse effects. With fluorescence dyes, MRI contrast agents, and PET tracers, real-time therapy response monitoring is conceivable. A nano platform with therapeutic and diagnostic capabilities holds great promise for personalized medicine and precision oncology. The present study discusses HNPs' biocompatibility, stability, immunogenicity, and long-term biosafety, which are crucial to the clinical translation of cancer theranostics. Further, in this in- -depth investigation, we investigated the design, synthesis, and multifunctional activities of HNPs for use in cancer theranostics.

RESUMEN

Gene therapy holds significant promise as a therapeutic approach for addressing a diverse range of diseases through the suppression of overexpressed proteins and the restoration of impaired cell functions. Developing a nanocarrier that can efficiently load and release genetic material into cells remains a challenge. The primary goal of this study is to develop formulations aimed to enhance the therapeutic potential of GapmeRs through technological approaches. To this end, lipid-polymeric hybrid nanoparticles (LPHNPs) with PLGA, DC-cholesterol, and DOPE-mPEG2000 were produced by conventional single-step nanoprecipitation (SSN) and microfluidic (MF) methods. The optimized nanoparticles by SSN have a size of 149.9 ± 18.07 nm, a polydispersity index (PdI) of 0.23 ± 0.02, and a zeta potential of (ZP) of 29.34 ± 2.44 mV, while by MF the size was 179.8 ± 6.3, a PdI of 0.24 ± 0.01, and a ZP of 32.25 ± 1.36 mV. Furthermore, LPHNPs prepared with GapmeR-protamine by both methods exhibit a high encapsulation efficiency of approximately 90%. The encapsulated GapmeR is completely released in 24 h. The LPHNP suspensions are stable for up to 6 h in 10% FBS at pH 5.4 and 7.4. By contrast, LPHNPs remain stable in suspension in 4.5% albumin at pH 7.4 for 24 h. Additionally, LPHNPs were successfully freeze-dried using trehalose in the range of 2.5-5% as cryoprotectant The LPHNPs produced by MF and SSN increase, 6 and 12 fold respectively, GapmeR cell uptake, and both of them reduce by 60-70% expression of Tob1 in 48 h.Our study demonstrates the efficacy of the developed LPHNPs as carriers for oligonucleotide delivery, offering valuable insights for their scale up production from a conventional bulk methodology to a high-throughput microfluidic technology.

RESUMEN

The intended research aims to explore the convection phenomena of a hybrid nanofluid composed of gold and silver nanoparticles. This research is novel and significant because there is a lack of existing studies on the flow behavior of hybrid nanoparticles with important physical properties of blood base fluids, especially in the case of sidewall ruptured dilated arteries. The implementation of combined nanoparticles rather than unadulterated nanoparticles is one of the most crucial elements in boosting the thermal conduction of fluids. The research methodology encompasses the utilization of advanced bio-fluid dynamics software for simulating the flow of the nanofluid. The physical context elucidates the governing equations of momentum, mass, momentum, and energy in terms of partial differential equations. The results are displayed in both tabular and graphical forms to demonstrate the numerical and graphical solutions. The effect of physical parameters on velocity distribution is illustrated through graphs. Furthermore, the study's findings are unique and original, and these computational discoveries have not been published by any researcher before. The finding implies that utilizing hybrid nanoparticles as drug carriers holds great promise in mitigating the effects of blood flow, potentially enhancing drug delivery, and minimizing its impact on the body.

Asunto(s)

Hemodinámica , Nanopartículas del Metal , Humanos , Nanopartículas del Metal/química , Oro/química , Simulación por Computador , Arterias , Plata/química , Nanopartículas/química , Modelos Cardiovasculares , Hidrodinámica

RESUMEN

Hybrid polypyrrole (PPy) nanoparticles were prepared using a low-temperature oxidative polymerization process in an acidic solution with polyethyleneimine (PEI) as a template and amine source. The results showed that the nanoparticles have an amorphous structure in the X-ray diffractogram and exhibited good dispersibility in water, uniform size, and a specific conductivity ranging from 0.1 to 6.9 S/cm. The particle size could be tuned from 85 to 300 nm by varying the reactant concentration. Undoping the samples with sodium hydroxide (NaOH) solution altered the optical absorption properties and surface roughness of the particles. However, it did not affect the particle size. The nanoparticles also exhibited optical sensing properties based on their UV-vis absorption changes with the pH. Moreover, nanoparticles could have potential applications in gene delivery and bio-adsorption for contaminant removal. This work demonstrates a simple and effective method for preparing hybrid polypyrrole nanoparticles with controllable size, dispersibility, and conductivity for various nanotechnology, biotechnology, and environmental engineering purposes.

RESUMEN

The present study concerns the preparation of hybrid nanostructures composed of carbon dots (CDs) synthesized in our lab and a double-hydrophilic poly(2-dimethylaminoethyl methacrylate-co-oligo(ethylene glycol) methyl ether methacrylate) (P(DMAEMA-co-OEGMA)) random copolymer through electrostatic interactions between the negatively charged CDs and the positively charged DMAEMA segments of the copolymer. The synthesis of P(DMAEMA-co-OEGMA) copolymer was conducted through RAFT polymerization. Furthermore, the copolymer was converted into a strong cationic random polyelectrolyte through quaternization of the amine groups of DMAEMA segments with methyl iodide (CH3I), and it was subsequently utilized for the complexation with the carbon dots. The molecular, physicochemical, and photophysical characterization of the aqueous solution of the copolymers and their hybrid nanoparticles was conducted using dynamic and electrophoretic light scattering (DLS, ELS) and spectroscopic techniques, such as UV-Vis, fluorescence (FS), and FT-IR spectroscopy. In addition, studies of their aqueous solution using DLS and ELS showed their responsiveness to external stimuli (pH, temperature, ionic strength). Finally, the interaction of selected hybrid nanoparticles with iron (III) ions was confirmed through FS spectroscopy, demonstrating their potential application for heavy metal ions sensing.