Colloidal Synthesis of Carbon Dot-ZnSe Nanoplatelet Van der Waals Heterostructures for Boosting Photocatalytic Generation of Methanol-Storable Hydrogen.

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.

Adipose Tissue Targeting Ultra-Small Hybrid Nanoparticles for Synergistic Photodynamic Therapy and Browning Induction in Obesity Treatment.

Photodynamic therapy (PDT), as a means of locally and rapidly inducing adipocyte death via light illumination, in combination with adipose browning induction, a more gradual and widespread effect that could transform white adipose tissue into thermogenic adipose tissue, manifests a promising approach to combat obesity. Herein, adipose-targeting ultra-small hybrid nanoparticles (Pep-PPIX-Baic NPs) composed of an adipose-targeting peptide, Fe3+, a photosensitizer (protoporphyrin IX), and a browning agent (baicalin) are introduced. Pep-PPIX-Baic NPs have been designed to simultaneously enhance the photodynamic effect and induce browning. After intravenous injection in obese mice, the hybrid nanoparticles can specifically accumulate in white adipose tissues, especially those rich in blood supply, and drive adipose reduction owing to the synergy of the PDT effect and baicalin browning induction. Overall, Pep-PPIX-Baic NPs exhibited superior anti-obesity potential through PDT synergistic with adipose browning induction. The designed multifunctional adipose-targeting hybrid nanoparticles present a prospective nanoplatform for obesity treatment.

Lipid polymer hybrid nanoparticles: a custom-tailored next-generation approach for cancer therapeutics.

Lipid-based polymeric nanoparticles are the highly popular carrier systems for cancer drug therapy. But presently, detailed investigations have revealed their flaws as drug delivery carriers. Lipid polymer hybrid nanoparticles (LPHNPs) are advanced core-shell nanoconstructs with a polymeric core region enclosed by a lipidic layer, presumed to be derived from both liposomes and polymeric nanounits. This unique concept is of utmost importance as a combinable drug delivery platform in oncology due to its dual structured character. To add advantage and restrict one's limitation by other, LPHNPs have been designed so to gain number of advantages such as stability, high loading of cargo, increased biocompatibility, rate-limiting controlled release, and elevated drug half-lives as well as therapeutic effectiveness while minimizing their drawbacks. The outer shell, in particular, can be functionalized in a variety of ways with stimuli-responsive moieties and ligands to provide intelligent holding and for active targeting of antineoplastic medicines, transport of genes, and theragnostic. This review comprehensively provides insight into recent substantial advancements in developing strategies for treating various cancer using LPHNPs. The bioactivity assessment factors have also been highlighted with a discussion of LPHNPs future clinical prospects.

Mitochondrion-targeted carboxymethyl chitosan hybrid nanoparticles loaded with Coenzyme Q10 protect cardiac grafts against cold ischaemia‒reperfusion injury in heart transplantation.

BACKGROUND: Heart transplantation (HT) has been approved as an optimal therapeutic regimen for patients with terminal-stage cardiac failure. However, cold ischaemia‒reperfusion (I/R) injury remains an unavoidable and outstanding challenge, which is a major factor in early graft dysfunction and an obstacle to long-term survival in HT. Cold I/R injury induces cardiac graft injury by promoting mitochondrial dysfunction and augmenting free radical production and inflammatory responses. We therefore designed a mitochondrion-targeted nanocarrier loaded with Coenzyme Q10 (CoQ10) (CoQ10@TNPs) for treatment of cold I/R injury after cardiac graft in a murine heterotopic cardiac transplantation model. METHODS: Hybrid nanoparticles composed of CaCO3/CaP/biotinylated-carboxymethylchitosan (CaCO3/CaP/BCMC) were synthesized using the coprecipitation method, and the mitochondria-targeting tetrapeptide SS31 was incorporated onto the surface of the hybrid nanoparticles through biotin-avidin interactions. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis were used for characterisation. In vitro, the hypoxia-reoxygenation model of H9c2 cells was employed to replicate in vivo cold I/R injury and treated with CoQ10@TNPs. The impact of CoQ10@TNPs on H9c2 cell injury was assessed by analysis of oxidative damage and apoptosis. In vivo, donor hearts (DHs) were perfused with preservation solution containing CoQ10@TNPs and stored in vitro at 4 °C for 12 h. The DHs were heterotopically transplanted and analysed for graft function, oxidative damage, apoptosis, and inflammatory markers 1 day post-transplantation. RESULTS: CoQ10@TNPs were successfully synthesized and delivered CoQ10 to the mitochondria of the cold ischaemic myocardium. In vitro experiments demonstrated that CoQ10@TNPs was taken up by H9c2 cells at 4 °C and localized within the mitochondria, thus ameliorating oxidative stress damage and mitochondrial injury in cold I/R injury. In vivo experiments showed that CoQ10@TNPs accumulated in DH tissue at 4 °C, localized within the mitochondria during cold storage and improved cardiac graft function by attenuating mitochondrial oxidative injury and inflammation. CONCLUSIONS: CoQ10@TNPs can precisely deliver CoQ10 to the mitochondria of cold I/R-injured cardiomyocytes to effectively eliminate mitochondrial reactive oxygen species (mtROS), thus reducing oxidative injury and inflammatory reactions in cold I/R-injured graft tissues and finally improving heart graft function. Thus, CoQ10@TNPs offer an effective approach for safeguarding cardiac grafts against extended periods of cold ischaemia, emphasizing the therapeutic potential in mitigating cold I/R injury during HT. These findings present an opportunity to enhance existing results following HT and broaden the range of viable grafts for transplantation.

Self-assembled Gallic acid loaded lecithin-chitosan hybrid nanostructured gel as a potential tool against imiquimod-induced psoriasis.

Increased thickness of the skin and hyperproliferation of keratinocyte cell is the main obstacle in the treatment of psoriasis. Gallic Acid (GA) has shown efficacious results against the hyperproliferation of keratinocytes while lipid-polymer loaded hybrid nanoparticles (LPHNs) have an edge over lipidic and polymeric nanoparticles considering drug loading, controlled release, stability, and retention. The LPHNs were optimized using Box-Behnken method and was further characterized by FTIR, DSC and Zetasizer. The optimized preparation demonstrated a size of 170.5 ± 0.087 nm and a PDI of 0.19 ± 0.0015, respectively. The confocal study has suggested that the hybrid nanosystem enhanced the drug penetration into the deeper layer with a higher drug release of 79 ± 0.001% as compared to the gallic acid-loaded gel. In addition, the formulation significantly reduced PASI score and splenomegaly without causing any serious irritation. The morphological study of the spleen suggested that the prepared formulation has well controlled the disease compared to the marketed formulation while maintaining a normal level of immune cells after treatment. Hence GALPHN could be accepted as one of the excellent vehicles for the topical conveyance of GA (gallic acid) due to enhanced penetration, and good retention, along with fewer side effects and higher efficacy of the GALPHN gel against imiquimod (IMQ) induced psoriasis.

Bioactive fatty acid analog-derived hybrid nanoparticles confer antibody-independent chemo-immunotherapy against carcinoma.

Typical chemo-immunotherapy against malignant carcinoma, is characterized by the combined application of chemotherapeutic agents and monoclonal antibodies for immune checkpoint blockade (ICB). Temporary ICB with antibodies would not depress tumor intrinsic PD-L1 expression and potential PD-L1 adaptive upregulation during chemotherapy, thus exerting limited immunotherapy efficacy. Herein, we developed novel polymer-lipid hybrid nanoparticles (2-BP/CPT-PLNs) for inducing PD-L1 degradation by inhibiting palmitoylation with bioactive palmitic acid analog 2-bromopalmitate (2-BP) to replace PD-L1 antibody (αPD-L1) for ICB therapy, thus achieving highly efficient antitumor immune via immunogenic cell death (ICD) induced by potentiated chemotherapy. GSH-responsive and biodegradable polymer-prodrug CPT-ss-PAEEP10 assisted as a cationic helper polymer could help to stabilize 2-BP/CPT-PLNs co-assembled with 2-BP, and facilitate the tumor site-specific delivery and intracellular release of water-insoluble camptothecin (CPT) in vivo. 2-BP/CPT-PLNs would reinforce cytotoxic CD8+ T cell-mediated antitumor immune response via promoting intratumoral lymphocytes cells infiltration and activation. 2-BP/CPT-PLNs significantly prevented melanoma progression and prolonged life survival of mice beyond the conventional combination of irinotecan hydrochloride (CPT-11) and αPD-L1. Our work first provided valuable instructions for developing bioactive lipid analogs-derived nanoparticles via lipid metabolism intervention for oncotherapy.

Heating Capacity and Biocompatibility of Hybrid Nanoparticles for Magnetic Hyperthermia Treatment.

Cancer is one of the deadliest diseases worldwide and has been responsible for millions of deaths. However, developing a satisfactory smart multifunctional material combining different strategies to kill cancer cells poses a challenge. This work aims at filling this gap by developing a composite material for cancer treatment through hyperthermia and drug release. With this purpose, magnetic nanoparticles were coated with a polymer matrix consisting of poly (L-co-D,L lactic acid-co-trimethylene carbonate) and a poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer. High-resolution transmission electron microscopy and selected area electron diffraction confirmed magnetite to be the only iron oxide in the sample. Cytotoxicity and heat release assays on the hybrid nanoparticles were performed here for the first time. The heat induction results indicate that these new magnetic hybrid nanoparticles are capable of increasing the temperature by more than 5 °C, the minimal temperature rise required for being effectively used in hyperthermia treatments. The biocompatibility assays conducted under different concentrations, in the presence and in the absence of an external alternating current magnetic field, did not reveal any cytotoxicity. Therefore, the overall results indicate that the investigated hybrid nanoparticles have a great potential to be used as carrier systems for cancer treatment by hyperthermia.

Selective Delivery of Tofacitinib Citrate to Hair Follicles Using Lipid-Coated Calcium Carbonate Nanocarrier Controls Chemotherapy-Induced Alopecia Areata.

Chemotherapy-induced alopecia (CIA) is one of the common side effects in cancer treatment. The psychological distress caused by hair loss may cause patients to discontinue chemotherapy, affecting the efficacy of the treatment. The JAK inhibitor, Tofacitinib citrate (TFC), showed huge potential in therapeutic applications for treating baldness, but the systemic adverse effects of oral administration and low absorption rate at the target site limited its widespread application in alopecia. To overcome these problems, we designed phospholipid-calcium carbonate hybrid nanoparticles (PL/ACC NPs) for a topical application to target deliver TFC. The results proved that PL/ACC-TFC NPs showed excellent pH sensitivity and transdermal penetration in vitro. PL/ACC NPs offered an efficient follicular targeting approach to deliver TFC in a Cyclophosphamide (CYP)-induced alopecia areata mouse model. Compared to the topical application of TFC solution, PL/ACC-TFC NPs significantly inhibited apoptosis of mouse hair follicles and accelerated hair growth. These findings support that PL/ACC-TFC NPs has the potential for topical application in preventing and mitigating CYP-induced Alopecia areata.

Hybrid Nanoplatforms Comprising Organic Nanocompartments Encapsulating Inorganic Nanoparticles for Enhanced Drug Delivery and Bioimaging Applications.

Organic and inorganic nanoparticles (NPs) have attracted significant attention due to their unique physico-chemical properties, which have paved the way for their application in numerous fields including diagnostics and therapy. Recently, hybrid nanomaterials consisting of organic nanocompartments (e.g., liposomes, micelles, poly (lactic-co-glycolic acid) NPs, dendrimers, or chitosan NPs) encapsulating inorganic NPs (quantum dots, or NPs made of gold, silver, silica, or magnetic materials) have been researched for usage in vivo as drug-delivery or theranostic agents. These classes of hybrid multi-particulate systems can enable or facilitate the use of inorganic NPs in biomedical applications. Notably, integration of inorganic NPs within organic nanocompartments results in improved NP stability, enhanced bioavailability, and reduced systemic toxicity. Moreover, these hybrid nanomaterials allow synergistic interactions between organic and inorganic NPs, leading to further improvements in therapeutic efficacy. Furthermore, these platforms can also serve as multifunctional agents capable of advanced bioimaging and targeted delivery of therapeutic agents, with great potential for clinical applications. By considering these advancements in the field of nanomedicine, this review aims to provide an overview of recent developments in the use of hybrid nanoparticulate systems that consist of organic nanocompartments encapsulating inorganic NPs for applications in drug delivery, bioimaging, and theranostics.

Core Shell Lipid-Polymer Hybrid Nanoparticles for Oral Bioavailability Enhancement of Ibrutinib via Lymphatic Uptake.

The purpose of this research was to develop ibrutinib (IBR)-loaded lipid-polymer hybrid nanoparticles (IBR-LPHNPs) to improve oral absorption by intestinal lymphatic uptake. IBR-LPHNPs were fabricated by nanoprecipitation method using poly(lactic-co-glycolic acid), lipoid S 100, and DSPE-MPEG 2000. The IBR-LPHNPs showed particle size of 85.27±3.82 nm, entrapment efficiency of 97.70±3.85%, and zeta potential of -24.9±3.08 mV respectively. Fourier transform infrared spectroscopy and differential scanning calorimetry study revealed compatibility between IBR and excipients. X-ray diffraction study showed the conversion of IBR into amorphous form. High-resolution transmission electron microscopic image displayed spherical-shaped, discrete layered polymeric core and lipid shell structure. The drug release from IBR-LPHNPs exhibited prolong release profile up to 48 h and was best fitted to Korsmeyer-Peppas model. Higher fluorescence intensity at the end of 2 h in the intestinal tissue confirmed the uptake of LPHNPs by Peyer's patches. The oral bioavailability of IBR was improved 22.52-fold with LPHNPs as compared to free IBR. The intestinal lymphatic uptake study in rats pretreated with cycloheximide confirmed the intestinal lymphatic uptake of IBR-LPHNPs. All the results conclusively showed that LPHNPs could be a promising approach to improve oral bioavailability of IBR.

Highlights on Cell-Penetrating Peptides and Polymer-Lipid Hybrid Nanoparticle: Overview and Therapeutic Applications for Targeted Anticancer Therapy.

Polymer-lipid hybrid nanoparticles (PLHNs) have been widely used as a vehicle for carrying anticancer owing to its unique framework of polymer and lipid combining and giving the maximum advantages over the lipid and polymer nanoparticle drug delivery system. Surface modification of PLHNs aids in improved targeting and active delivery of the encapsulated drug. Therefore, surface modification of the PLHNs with the cell-penetrating peptide is explored by many researchers and is explained in this review. Cell-penetrating peptides (CPPs) are made up of few amino acid sequence and act by disrupting the cell membrane and transferring the cargos into the cell. Ideally, we can say that CPPs are peptide chains which are cell specific and are biocompatible, noninvasive type of delivery vehicle which can transport siRNA, protein, peptides, macromolecules, pDNA, etc. into the cell effectively. Therefore, this review focuses on the structure, type, and method of preparation of PLHNs also about the uptake mechanism of CPPs and concludes with the therapeutic application of PLHNs surface modified with the CPPs and their theranostics.

Development and In Vitro Evaluation of Crizotinib-Loaded Lipid-Polymer Hybrid Nanoparticles Using Box-Behnken Design in Non-small Cell Lung Cancer.

The goal of the study was to produce, optimize, characterize, and compare crizotinib-loaded lipid-polymer hybrid nanoparticles (CL-LPHNPs), representing a novel contribution to the existing literature, and to determine their anticancer activity in non-small cell lung cancer cells (NSCLC). Box-Behnken design was used to investigate the effect of three independent variables: polymer amount (X1), soy phosphatidylcholine (X2), and DSPE-PEG (X3), on three responses: particle size (Y1), polydispersity index (Y2), and zeta potential (Y3). Different parameters were evaluated on the optimized LPHNP formulations such as encapsulation efficiency, drug release study, transmission electron microscopy (TEM) image analysis, and in vitro cell evaluations. The mean particle size of the optimized formulation is between 120 and 220 nm with a PDI< 0.2 and a zeta potential of -10 to -15 mV. The encapsulation efficiency values of crizotinib-loaded PLGA-LPHNPs (CL-PLGA-LPHNPs) and crizotinib-loaded PCL-LPHNPs (CL-PCL-LPHNPs) were 79.25±0.07% and 70.93±1.81%, respectively. Drug release study of CL-PLGA-LPHNPs and CL-PCL-LPHNPs showed a controlled and sustained release pattern as a result of core-shell type. Additionally, after 48 h, CL-PLGA-LPHNPs and CL-PCL-LPHNPs significantly reduced the viability of NCI-H2228 cells compared to free crizotinib. Moreover, CL-PLGA-LPHNPs and CL-PCL-LPHNPs exhibited a significant decrease in RAS, RAF, MEK, and ERK gene/protein expression levels after 48-h incubation. In conclusion, this pioneering study introduces lipid-polymer hybrid nanoparticles containing crizotinib as a novel treatment approach, uniting the advantages of a polymeric core and a lipid shell. The successful formulation optimization using Box-Behnken design yielded nanoparticles with adjustable size, remarkable stability, high drug loading, and a customizable drug release profile. Extensive investigations of key parameters, including particle size, PDI, ZP, TEM analysis, drug release, EE%, and in vitro evaluations, validate the potential of these nanoparticles. Moreover, the examination of two different polymers, PLGA and PCL, highlights their distinct impacts on nanoparticle performance. This research opens up new prospects for advanced therapeutic interventions with lipid-polymer hybrid nanoparticles.

Tuning the Electronic Properties of Platinum in Hybrid-Nanoparticle Assemblies for use in Hydrogen Evolution Reaction.

Platinum is the best electrocatalyst for the hydrogen evolution reaction (HER). Here, we demonstrate that by contact electrification of Pt nanoparticle satellites on a gold or silver core, the Fermi level of Pt can be tuned. The electronic properties of Pt in such hybrid nanocatalysts were experimentally characterized by X-ray photoelectron spectroscopy (XPS) and surface-enhanced Raman scattering (SERS) with the probe molecule 2,6-dimethyl phenyl isocyanide (2,6-DMPI). Our experimental findings are corroborated by a hybridization model and density functional theory (DFT) calculations. Finally, we demonstrate that tuning of the Fermi level of Pt results in reduced or increased overpotentials in water splitting.

Galvanic Restructuring of Exsolved Nanoparticles for Plasmonic and Electrocatalytic Energy Conversion.

There is a growing need to control and tune nanoparticles (NPs) to increase their stability and effectiveness, especially for photo- and electrochemical energy conversion applications. Exsolved particles are well anchored and can be re-shaped without changing their initial location and structural arrangement. However, this usually involves lengthy treatments and use of toxic gases. Here, the galvanic replacement/deposition method is used, which is simpler, safer, and leads to a wealth of new hybrid nanostructures with a higher degree of tailorability. The produced NiAu bimetallic nanostructures supported on SrTiO3 display exceptional activity in plasmon-assisted photoelectrochemical (PEC) water oxidation reactions. In situ scanning transmission electron microscopy is used to visualize the structural evolution of the plasmonic bimetallic structures, while theoretical simulations provide mechanistic insight and correlate the surface plasmon resonance effects with structural features and enhanced PEC performance. The versatility of this concept in shifting catalytic modes to the hydrogen evolution reaction is demonstrated by preparing hybrid NiPt bimetallic NPs of low Pt loadings on highly reduced SrTiO3 supports. This powerful methodology enables the design of supported bimetallic nanomaterials with tunable morphology and catalytic functionalities through minimal engineering.

Advances in Nanomedicine Design: Multidisciplinary Strategies for Unmet Medical Needs.

Globally, a rising burden of complex diseases takes a heavy toll on human lives and poses substantial clinical and economic challenges. This review covers nanomedicine and nanotechnology-enabled advanced drug delivery systems (DDS) designed to address various unmet medical needs. Key nanomedicine and DDSs, currently employed in the clinic to tackle some of these diseases, are discussed focusing on their versatility in diagnostics, anticancer therapy, and diabetes management. First-hand experiences from our own laboratory and the work of others are presented to provide insights into strategies to design and optimize nanomedicine- and nanotechnology-enabled DDS for enhancing therapeutic outcomes. Computational analysis is also briefly reviewed as a technology for rational design of controlled release DDS. Further explorations of DDS have illuminated the interplay of physiological barriers and their impact on DDS. It is demonstrated how such delivery systems can overcome these barriers for enhanced therapeutic efficacy and how new perspectives of next-generation DDS can be applied clinically.

Enhanced heat transfer characteristics of the mini hexagonal tube heat sink using hybrid nanofluids.

The thermal performance of different hybrid nanofluids on the mini hexagonal tube heat sink has been investigated experimentally. Al2O3/SiO2-DIW, Al2O3/CuO-DIW, and CuO/SiO2-DIW nanofluids have been used as the working fluids. The aggregate of 0.01 volume fraction of Al2O3, CuO, and SiO2nanoparticles for hybridizing ratios (80:20) has been considered to prepare deionized water-based hybrid nanofluids. The thermal performance of three different hybrid nanofluids inside the mini hexagonal tube heat sink has been assessed. The varying volumetric flow rates of 15-50 lph have been maintained on the hexagonal tube side and 50 lph on the mini passage side. Herein, the proposed hexagonal-shaped heat sink provides a larger heat contact surface to exchange the heat between the hybrid nanofluids and hot DIW. It is divulged that the increase in the volume flow rate of nanofluids promotes the higher Brownian motion, leading to an increase in convective heat transfer. Amongst three hybrid nanofluids, CuO/SiO2-DIW nanofluids have revealed a slight increase in pumping power while increasing the volume flow rate. From the experimental results, it is shown that the heat transfer coefficient, effectiveness, and Nusselt number have been improved by 54.5%, 42%, and 28.4%, respectively, for Al2O3/CuO-DIW nanofluids. Thus, Al2O3/CuO-DIW nanofluid can be deemed to be an efficient working fluid for the miniature heat sinks to accelerate the heat transfer rates.

EGF-functionalized lipid-polymer hybrid nanoparticles of 5-fluorouracil and sulforaphane with enhanced bioavailability and anticancer activity against colon carcinoma.

The present research work describes development of dual drug-loaded lipid-polymer hybrid nanoparticles (LPHNPs) of anticancer therapeutics for the management of colon cancer. The epidermal growth factor (EGF)-functionalized LPHNPs coloaded with 5-fluorouracil (FU) and sulforaphane (SFN) were prepared by one-step nanoprecipitation method. Box-Behnken design was applied for optimizing the material attributes and process parameters. The optimized LPHNPs revealed particle size 198 nm, polydispersity index 0.3, zeta potential -25.3 mV, and drug loading efficiency 19-20.3% for 5-FU and SFN, respectively. EGF functionalization on LPHNPs was confirmed from positive magnitude of zeta potential to 21.3 mV as compared with the plain LPHNPs. In vitro drug release performance indicated sustained and non-Fickian mechanism release nature of the drugs from LPHNPs. Anticancer activity evaluation in HCT-15 colon cancer cells showed significant reduction (p < 0.001) in the cell growth and cytotoxicity of the investigated drugs from various treatments in the order: EGF-functionalized LPHNPs > plain LPHNPs > free drug suspensions. Overall, the research work corroborated improved treatment efficacy of EGF-functionalized LPHNPs for delivering chemotherapeutic agents for the management of colon carcinoma.

Nanoparticle-mediated selective Sfrp-1 silencing enhances bone density in osteoporotic mice.

Osteoporosis (OP) is characterized by a loss in bone mass and mineral density. The stimulation of the canonical Wnt/ß-catenin pathway has been reported to promote bone formation, this pathway is controlled by several regulators as secreted frizzled-related protein-1 (Sfrp-1), antagonist of the pathway. Thus, Sfrp-1 silencing therapies could be suitable for enhancing bone growth. However, the systemic stimulation of Wnt/ß-catenin has been correlated with side effects. This work hypothesizes the administration of lipid-polymer NPs (LPNPs) functionalized with a MSC specific aptamer (Apt) and carrying a SFRP1 silencing GapmeR, could favor bone formation in OP with minimal undesired effects. Suitable SFRP1 GapmeR-loaded Apt-LPNPs (Apt-LPNPs-SFRP1) were administered in osteoporotic mice and their biodistribution, toxicity and bone induction capacity were evaluated. The aptamer functionalization of the NPs modified their biodistribution profile showing a four-fold increase in the bone accumulation and a ten-fold decrease in the hepatic accumulation compared to naked LPNPs. Moreover, the histological evaluation revealed evident changes in bone structure observing a more compact trabecular bone and a cortical bone thickness increase in the Apt-LPNPs-SFRP1 treated mice with no toxic effects. Therefore, these LPNPs showed suitable properties and biodistribution profiles leading to an enhancement on the bone density of osteoporotic mice.

A cationic cyclodextrin derivative-lipid hybrid nanoparticles for gene delivery effectively promotes stability and transfection efficiency.

Genetic medicines hold great promise for treatment of a number of diseases; however, the development of effective gene delivery carrier is still a challenge. The commonly used gene carrier liposomes and cationic polymers have limited their clinical application due to their respective disadvantages. Lipid-polymer hybrid nanoparticles (LHNPs) are novel drug delivery system that exhibit complementary characteristics of both polymeric nanoparticles and liposomes. In this account, we developed the α-cyclodextrin-conjugated generation-2 polyamidoamine dendrimers-lipids hybrid nanoparticles (CDG2-LHNPs) for gene delivery. The pDNA/CDG2-LHNPs was stable during 15 days of storage period both at 4 °C, 25 °C, and 37 °C, whereas the particle size of pDNA/CDG2 and pDNA/liposomes dramatically increased after storage at 4 °C for 8 h. CDG2-LHNPs showed significantly superior transfection efficiencies compared to either CDG2 or liposomes. The mechanism of high transfection efficiency of pDNA/CDG2-LHNPs was further explored using pharmacological inhibitors chlorpromazine, filipin, and cytochalasion D. The result demonstrated that cell uptake of pDNA/CDG2-LHNPs was mediated by clathrin-mediated endocytosis (CME), caveolae-mediated endocytosis (CvME), and macropinocytosis together. pDNA/CDG2-LHNPs were more likely be taken up by cells through CvME, which avoided lysosomal degradation to a large extent. Moreover, the liposome component of pDNA/CDG2-LHNPs increased its cell uptake efficiency, and the CDG2 polymer component increased its proton buffer capacity, so the hybrid nanoparticles taken up by CME could also successfully escape from the lysosome. CDG2-LHNPs with stability and high-transfection efficiency overcome the shortcomings of liposomes and polymers applied separately, and have great potential for gene drug delivery.

Hybrid Nanoparticles and Composite Hydrogel Systems for Delivery of Peptide Antibiotics.

The growing number of drug-resistant pathogenic bacteria poses a global threat to human health. For this reason, the search for ways to enhance the antibacterial activity of existing antibiotics is now an urgent medical task. The aim of this study was to develop novel delivery systems for polymyxins to improve their antimicrobial properties against various infections. For this, hybrid core-shell nanoparticles, consisting of silver core and a poly(glutamic acid) shell capable of polymyxin binding, were developed and carefully investigated. Characterization of the hybrid nanoparticles revealed a hydrodynamic diameter of approximately 100 nm and a negative electrokinetic potential. The nanoparticles demonstrated a lack of cytotoxicity, a low uptake by macrophages, and their own antimicrobial activity. Drug loading and loading efficacy were determined for both polymyxin B and E, and the maximal loaded value with an appropriate size of the delivery systems was 450 µg/mg of nanoparticles. Composite materials based on agarose hydrogel were prepared, containing both the loaded hybrid systems and free antibiotics. The features of polymyxin release from the hybrid nanoparticles and the composite materials were studied, and the mechanisms of release were analyzed using different theoretical models. The antibacterial activity against Pseudomonas aeruginosa was evaluated for both the polymyxin hybrid and the composite delivery systems. All tested samples inhibited bacterial growth. The minimal inhibitory concentrations of the polymyxin B hybrid delivery system demonstrated a synergistic effect when compared with either the antibiotic or the silver nanoparticles alone.