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Herein, in a one-pot method, the reduced graphene oxide layers with the assistance of multiwalled carbon nanotubes were decorated to provide a suitable space for the in situ growth of CoNi2S4, and the porphyrins were incorporated into the layers as well to increase the sensitivity of the prepared nanostructure. The prepared nanocomposite can establish π–π interactions between the genetic material and on the surface of porphyrin rings. Also, hydrogen bonds between genetic domains and the porphyrin’ nitrogen and the surface hydroxyl groups are probable. Furthermore, the potential donor–acceptor relationship between the d7 transition metal, cobalt, and the genetic material provides a suitable way to increase the interaction and gene loading , and transfections. The reason for this phenomenon was optimized to increase the EGFP by up to 17.9%. Furthermore, the sensing ability of the nanocomposite towards H2O2 was investigated. In this regard, the limit of detection of the H2O2 obtained 10 µM. Also, the in situ biosensing ability in the HEK-293 and PC12 cell lines was evaluated by the addition of PMA. The nanocomposite showed the ability to detect the released H2O2 after adding the minimum amount of 120 ng/mL of the PMA.

Herein, the NH2-UiO-66 metal organic framework (MOF) has been green synthesized with the assistance of high gravity to provide a suitable and safe platform for drug loading. The NH2-UiO-66 MOF was characterized using a field-emission scanning electron microscope, transmission electron microscope (TEM), X-ray diffraction, and zeta potential analysis. Doxorubicin was then encapsulated physically on the porosity of the green MOF. Two different stimulus polymers, p(HEMA) and p(NIPAM), were used as the coating agents of the MOFs. Doxorubicin was loaded onto the polymer-coated MOFs as well, and a drug payload of more than 51% was obtained, which is a record by itself. In the next step, pCRISPR was successfully tagged on the surface of the modified MOFs, and the performance of the final nanosystems were evaluated by the GFP expression. In addition, successful loadings and internalizations of doxorubicin were investigated via confocal laser scanning microscopy. Cellular images from the HeLa cell line for the UiO-66@DOX@pCRISPR and GMA-UiO-66@DOX@pCRISPR do not show any promising and successful gene transfections, with a maximum EGFP of 1.6%; however, the results for the p(HEMA)-GMA-UiO-66@DOX@pCRISPR show up to 4.3% transfection efficiency. Also, the results for the p(NIPAM)-GMA-UiO-66@DOX@pCRISPR showed up to 6.4% transfection efficiency, which is the first and superior report of a MOF-based nanocarrier for the delivery of pCRISPR. Furthermore, the MTT assay does not shown any critical cytotoxicity, which is a promising result for further biomedical applications. At the end of the study, the morphologies of all of the nanomaterials were screened after drug and gene delivery procedures and showed partial degradation of the nanomaterial. However, the cubic structure of the MOFs has been shown in TEM, and this is further proof of the stability of these green MOFs for biomedical applications.

With significant advancements in research technologies, and an increasing global population, microfluidic and nanofluidic systems (such as point-of-care, lab-on-a-chip, organ-on-a-chip, etc) have started to revolutionize medicine. Devices that combine micron and nanotechnologies have increased sensitivity, precision and versatility for numerous medical applications. However, while there has been extensive research on microfluidic and nanofluidic systems, very few have experienced wide-spread commercialization which is puzzling and deserves our collective attention. For the above reasons, in this article, we review research advances that combine micro and nanotechnologies to create the next generation of nanomaterial-based microfluidic systems, the latest in their commercialization success and failure and highlight the value of these devices both in industry and in the laboratory.

The therapeutic effects of carotenoids as dietary supplements to control or even treat some specific diseases including diabetic retinopathy, cardiovascular diseases, bacterial infections, as well as breast, prostate, and skin cancer are discussed in this review and also thoughts on future research for their widespread use are emphasized. From the stability standpoint, carotenoids have low bioavailability and bioaccessibility owing to their poor water solubility, deterioration in the presence of environmental stresses such as oxygen, light, and high heat as well as rapid degradation during digestion. Nanoencapsulation technologies as wall or encapsulation materials have been increasingly used for improving food product functionality. Nanoencapsulation is a versatile process employed for the protection, entrapment, and the delivery of food bioactive products including carotenoids from diverse environmental conditions for extended shelf lives and for providing controlled release. Therefore, we present here, recent (mostly during the last five years) nanoencapsulation methods of carotenoids with various nanocarriers. To us, this review can be considered as the first highlighting not only the potential therapeutic effects of carotenoids on various diseases but also their most effective nanodelivery systems.HighlightsBioactive compounds are of deep interest to improve food properties.Carotenoids (such as β-carotene and xanthophylls) play indispensable roles in maintaining human health and well-being.A substantial research effort has been carried out on developing beneficial nanodelivery systems for various carotenoids.Nanoencapsulation of carotenoids can enhance their functional properties.Stable nanoencapsulated carotenoids could be utilized in food products.

A Zn-Rich (GaN)1−x(ZnO)x nanostructure was synthesized with the assistance of a high-gravity technique in order to reduce the reaction time and temperature. The synthesized inorganic nanomaterial has been applied in both drug and gene delivery systems, and as the first fully inorganic nanomaterial, it was investigated in a comprehensive cellular investigation as well. In order to increase the potential bioavailability, as well as the interactions with the pCRISPR, the nanomaterial was enriched with additional Zn ions. The nanomaterial and the final nanocarrier were characterized at each step before and after any biological analysis via FESEM, AFM, TEM, FTIR and XRD. The polymer coated nanosystems were fully characterized, and their sustained DOX delivery were investigated as well as the comprehensive cytotoxicity investigations on HEK-293, PC12, HepG2 and HeLa cell lines after 24, 48 and 72 h of treatment, which showed that the nanomaterial had acceptable and very good cell viability at a minimum concentration of 0.1 μg mL−1 and a maximum concentration of 10 μg mL−1. Also, after coating with chitosan and alginate, the relative cell viability on all of the cell lines increased in the range of 2.7% to 18.9%. In the next step, the nanosystems were tagged with pCRISPR to analyze the potential application in the co-delivery of drug and gene. The confocal laser scanning microscopy (CLSM) images of the 4′,6-diamidino-2-phenylindole (DAPI) stained DOX showed that the Zn-rich (GaN)1−x(ZnO)x nanosystem has lower cellular density than the chitosan and alginate coated nanosystems. However, all of them showed acceptable and suitable localization of DOX into the nanostructure and the into the cells after the drug delivery procedure, along with sustained behaviors at different pH values. Furthermore, the CLSM images of HEK-293 and HeLa cell lines showed the successful delivery of pCRISPR into the cells, and the enhanced green fluorescent protein (EGFP) reached up to 9.3% for the HeLa cell line, which is a record by itself. In addition, the exact morphologies of the nanosystems before and after drug and gene delivery procedures were investigated via FESEM and TEM, and the results showed that in the presence of polymer coating, the morphology of the substrates was intact.

Infectious diseases (ID) are serious threats against the global health and socio-economic conditions. Vaccination usually plays a key role in disease prevention, however, insufficient efficiency or immunogenicity may be quite challenging. Using the advanced vectors for delivery of vaccines with suitable efficiency, safety, and immune-modulatory activity, and tunable characteristics could be helpful, but there are no systematic reviews confirming the capabilities of the vaccine delivery systems for covering various types of pathogens. Furthermore, high rates of the infections, transmission, and fatal ratio and diversity of the pathogens and infection mechanisms may negatively influence vaccine effectiveness. The absence of highly-effective antibiotics against the resistant strains of bacteria and longevity of antibiotic testing have provoked increasing needs towards the application of more accurate and specific theranostic strategies including the nanotechnology-based ones. Nanobionics which is based on the charge storage and transport in the molecular structures, could be of key value in the molecular diagnostic tests and highly-specific electro-analytical methods or devices. Such devices based on the early disease diagnostics might be of critical significance against various types of diseases. This article highlights the significance of nanobionics against ID.

In this study, electrospun Poly(vinyl alcohol)/Chitosan-g-Poly (N-vinyl imidazole) (PVA/CS-g-PNVIM) wound dressing containing Titanium dioxide/Curcumin (CUR) was prepared as a novel wound healing system with multifunctional properties, including wound closure, drug release, and antibacterial activity. The wound dressing nanofibers system's mechanical, structural, and biological properties were investigated using tensile testing, degradation, X-ray diffraction, Scanning electron microscopy, Fourier transformed infrared spectroscopy, drug release, and in vivo studies. The nanofiber dressing showed excellent mechanical and hydrolytic degradation stability. CS-g-PNVIM-based nanofibers showed excellent antibacterial activity against both Escherichia coli and Staphylococcus aureus in just 1 h with 90 % growth inhibition, with no cytotoxicity to normal fibroblast cells. The animal studies showed that the wound healing and tissue regeneration process by CS-g-PNVIM-based nanofibers were faster than the control group and was completed in 14 days. In conclusion, the CS-g-PNVIM-based nanofibers are potentially promising for biocompatible antibacterial wound dressing applications with proper exudate absorption.

The major current focus on treating rheumatoid arthritis is to put an end to long-term treatments and instead, specifically block widespread immunosuppression by developing antigen-specific tolerance, while also permitting an intact immune response toward other antigens to occur. There have been promising preclinical findings regarding adoptive Treg cells immunotherapy with a critically responsible function in the prevention of autoimmunity, tissue repair and regeneration, which make them an attractive candidate to develop effective therapeutic approaches to achieve this interesting concept in many human immune-mediated diseases, such as rheumatoid arthritis. Ex vivo or invivo manipulation protocols are not only utilized to correct Treg cells defect, but also to benefit from their specific immunosuppressive properties by identifying specific antigens that are expressed in the inflamedjoint. The methods able to address these deficiencies can be considered as a target for immunity interventions to restore appropriate immune function.

With continual rapid developments in the biomedical field and understanding of the important mechanisms and pharmacokinetics of biological molecules, controlled drug delivery systems (CDDSs) have been at the forefront over conventional drug delivery systems. Over the past several years, scientists have placed boundless energy and time into exploiting a wide variety of excipients, particularly diverse polymers, both natural and synthetic. More recently, the development of nano polymer blends has achieved noteworthy attention due to their amazing properties, such as biocompatibility, biodegradability and more importantly, their pivotal role in controlled and sustained drug release in vitro and in vivo. These compounds come with a number of effective benefits for improving problems of targeted or controlled drug and gene delivery systems; thus, they have been extensively used in medical and pharmaceutical applications. Additionally, they are quite attractive for wound dressings, textiles, tissue engineering, and biomedical prostheses. In this sense, some important and workable natural polymers (namely, chitosan (CS), starch and cellulose) and some applicable synthetic ones (such as poly-lactic-co-glycolic acid (PLGA), poly(lactic acid) (PLA) and poly-glycolic acid (PGA)) have played an indispensable role over the last two decades for their therapeutic effects owing to their appealing and renewable biological properties. According to our data, this is the first review article highlighting CDDSs composed of diverse natural and synthetic nano biopolymers, blended for biological purposes, mostly over the past five years; other reviews have just briefly mentioned the use of such blended polymers. We, additionally, try to make comparisons between various nano blending systems in terms of improved sustained and controlled drug release behavior.

Dual-targeted drug delivery system has established their reputation as potent vehicles for cancer chemotherapies. Herein, gemcitabine (Gem) was conjugated to human serum albumin (HSA) via dithiodipropionic anhydride to fabricate Gem-HSA nanoparticles. It was hypothesized that this system can enhance the low stability of Gem and can improve its intracellular delivery. Furthermore, folate was applied as targeting agent on HSA nanoparticles for increasing the tumor selectivity of Gem. To evaluate the structural properties of synthesized products, 1 H NMR and FT-IR were performed. Moreover, HPLC was implemented for confirming the conjugation between HSA and Gem. Nanoparticles have shown spherical shape with negative charge. The release rate of Gem was dependent to the concentration of glutathione and pH. Folate-targeted HSA nanoparticles have shown higher cytotoxicity, cellular uptake, and apoptosis induction on folate receptor overexpressing MDA-MB-231 cells in comparison to non-targeted nanoparticles. Finally, it is considered that the developed dual-targeted nanoparticles would be potent in improving the stability and efficacy of intracellular delivery of Gem and its selective delivery to cancer cells.

Uncontrolled distribution of nanoparticles (NPs) within the body can significantly decrease the efficiency of drug therapy and is considered among the main restrictions of NPs application. ...

Rod-like mesoporous silica nanoparticles with pH-responsive amphiphilic hyperbranched polyester shells were prepared for doxorubicin (DOX) delivery. First, rod-shaped mesoporous silica nanoparticles (MSNs) were obtained, then hydrophobic hyperbranched polyester Boltorn H40 (H40) was grafted on their surface. The H40 coated MSNs were next treated with amine-functionalized polyethylene glycol (PEG) to achieve the hydrophilic and pH-responsive material denoted as PEG-H40-MSNs. The experimental results showed that PEG-H40-MSNs were successfully synthesized. BET analysis showed that rod MSNs exhibits a type IV standard isotherm. TEM revealed that the thin gray polymer layer was formed around the SBA-15 particle with a diameter of around 150 nm. DOX was effectively loaded, which can be released according to the ambient pH inside the cell as follow: at pH 7.4, only 9.7% of the DOX was released after 48 h; as the pH decreased to 5.5, the cumulative release reached to 49% at the same time. PEG-H40-MSNs showed less than 1.6% of hemolytic activity and a slight effect on the liver and kidney of treated mice were observed at a high disposal dosage implying negligible toxicities were caused by PEG-H40-MSNs in both in vitro hemolysis analysis and in vivo biochemical in mice. However, the in vitro cytotoxicity evaluation of the DOX-PEG-H40-MSNs showed that the cell cytotoxicity of both pure DOX and DOX-loaded PEG-H40-MSNs generally enhanced by increasing the concentration of DOX. Graphical abstract Schematic of cellular uptake and DOX release of PEG-H40-MSNs nanoparticle.

Mitochondria have been recognized as important targets in cancer therapy due to their role in the respiratory process of cells. One approach employed for mitochondrion targeting is conjugation of a delocalized cation such as triphenylphosphonium (TPP), with antineoplastic agents, for instance paclitaxel (PTX). In cell cytoplasm, TPP-PTX can come close to mitochondria due to its high positive charge, which has a strong tendency toward the enhanced negative charge of mitochondria. The esteric bond of TPP-PTX can break down in the acidic environment of tumor cells and release the PTX, which can act directly on mitochondria to kill tumor cells. TPP-PTX was synthesized in three steps: Succinic anhydride (SUC) reacted with PTX to achieve succinyl paclitaxel (SUC-PTX), which has an acid-labile esteric bond. Then 2-triphenylphosphonium ethylammonium (ATPP) was prepared by attaching 2-bromoethylammunium bromide to TPP. Finally, a TPP-PTX prodrug was synthesized by attaching these materials. The products of all steps were characterized by thin-layer chromatography (TLC), infrared spectroscopy (IR), and nuclear magnetic resonance (1H NMR, 13C NMR). The purity of the products was determined by HPLC methods. TPP-PTX, as a prodrug, was loaded in to human serum albumin (HSA) nanoparticles by a method inspired by nab-technology with 130–160 nm particle size distribution, PdI=0.166 and Zeta potential −12.6 mV.

BACKGROUND: Imatinib is a platelet-derived growth factor receptor (PDGFR) inhibitor with very low water solubility. Previous studies in atherosclerosis have shown that PDGFR activity has an egregious effect on vascular disease and progression of atherosclerosis. Specific ligands of atherosclerotic plaques can be used for targeting of nanoparticles. Studies in atherosclerosis proved that stabilin-2 is a glycoprotein which exists abundantly in atherosclerotic plaques and it is produced from both macrophages and endothelial cells. OBJECTIVES: The objective of this study is the targeting drug delivery to atherosclerotic plaques by using imatinib-loaded nanoparticles modified by S2P peptide. METHODS: The imatinib-loaded nanoparticles were fabricated through a modified emulsion/solvent evaporation technique. After fabricating PLGA nanoparticles, maleimide PEG was used as linker between PLGA nanoparticles and S2P peptide. Because of presence cysteine in both side of S2P peptide, maleimide formed a thiolether linkage by thiol group of cysteine. Then the physicochemical analysis like H-NMR, FT-IR, DSC, SEM, particle size, zeta potential, and drug release were studied. RESULTS: Stabilin-2 peptide with sequence of CRTLTVRKC is a specific ligand to stabilin-2, so it was synthesized for using as the targeting agent for atherosclerosis. S2P peptide conjugation to the surface of nanoparticles was proved by H-NMR and FT-IR, and the percentage of S2P peptide in nanoparticles was 1.3%. The final nanoparticles were spherical and their size were 183 nm. The loading capacity of the imatinib-loaded nanoparticles was 5.05%. The sustained release profile was observed for peptide targeted nanoparticles. CONCLUSION: The chosen method was simple, reproducible, and specific in peptide conjugation of nanoparticles for targeting delivery to atherosclerotic regions. [Figure: see text]

For effective treatment of infected bone, it is essential to use local drug delivery systems with the ability to deliver both antibiotics and osteoinductive factors. Herein, a pH-sensitive silk fibroin (SF)/sodium alginate (SA) hydrogel scaffolds containing teicoplanin (TEC) and phenamil (PM) loaded SF nanoparticles (PMSFNPS) are introduced for treating chronic osteomyelitis. The TEC and PM showed a sustained- and pH-sensitive release behavior from SF/SA hydrogel. The higher release rate was seen in an alkaline pH in comparison to neutral and acidic pH during 10 days. The eluted TEC maintained its antibacterial activity of75 % during 35 days and in three different pH values (5.5, 7.4, and 8.5). The cellular study indicated that the scaffolds containing PMSFNPs could promote the cell viability, ALP activity, and matrix mineralization. Moreover, the in vivo effectiveness of hydrogel scaffolds were analyzed with radiography, histological and Immunohistochemistry evaluations. The lower infection and higher regeneration were observed in methicillin-resistant Staphylococcus aureus (MRSA) infected rat bone treated with hydrogel scaffold containing PMSFNPs and TEC compared to other groups. Consequently, this dual-drug delivery system could be a hopeful approach for effective treatment of chronic bone infection.

Super-paramagnetic iron oxide nanoparticles (SPIONs) are known as promising theranostic nano-drug carriers with magnetic resonance imaging (MRI) properties. Applying the herbaceous components with cytotoxic effects as cargos can suggest a new approach in the field of cancer-therapy. In this study mesoporous silica coated SPIONs (mSiO2@SPIONs) containing curcumin (CUR) and silymarin (SIL) were prepared and evaluated on breast cancer cell line, MCF-7.Nanoparticles (NPs) were formulated by reverse microemulsion method and characterized by DLS, SEM and VSM. The in vitro drug release, cellular cytotoxicity, and MRI properties of NPs were determined as well. The cellular uptake of NPs by MCF-7 cells was investigated through LysoTracker Red staining using confocal microscopy.The MTT results showed that the IC50 of CUR + SIL loaded mSiO2@SPIONs was reduced about 50% in comparison with that of the free drug mixture. The NPs indicated proper MRI features and cellular uptake through endocytosis.In conclusion the prepared formulation may offer a novel theranostic system for breast cancer researches.

Fast, efficient, and accurate detection of SARS-CoV-2 spike antigen is pivotal to control the spread and reduce the mortality of COVID-19. Nevertheless, the sensitivity of available nanobiosensors to detect recombinant SARS-CoV-2 spike antigen seems insufficient. As a proof-of-concept, MOF-5/CoNi

The aim of the present study was to investigate the therapeutic potential of budesonide- (BDS-) loaded hyaluronic acid nanoparticles (HANPs) for treatment of inflammatory bowel disease (IBD) using an acute model of colitis in rats. The therapeutic efficacy of BDS-loaded HANPs in comparison with an aqueous suspension of the drug with the same dose (30 μg/kg) was investigated 48 h following induction of colitis by intrarectal administration of acetic acid 4% in rats. Microscopic and histopathologic examinations were conducted in inflamed colonic tissue. Tissue concentration of tumor necrosis factor (TNF)-α was assessed by ELISA assay kit, while the activity of myeloperoxidase (MPO) was measured spectrophotometrically. Results from in vivo evaluations demonstrated that administrations of BDS-HANPs ameliorated the general endoscopic appearance, quite close to the healthy animals with no signs of inflammation and reduced the cellular infiltration, as well as the TNF-α level, and the MPO activity. It was found that delivery by BDS-loaded HANPSs alleviated the induced colitis significantly better than the same dose of the free drug. These data further suggest the potential of HANPs as a targeted drug delivery system to the inflamed colon mucosa.

Metal–organic frameworks (MOFs) have been widely used as porous nanomaterials for different applications ranging from industrial to biomedicals. An unpredictable one-pot method is introduced to synthesize NH2-MIL-53 assisted by high-gravity in a greener media for the first time. Then, porphyrins were deployed to adorn the surface of MOF to increase the sensitivity of the prepared nanocomposite to the genetic materials and in-situ cellular protein structures. The hydrogen bond formation between genetic domains and the porphyrin’ nitrogen as well as the surface hydroxyl groups is equally probable and could be considered a milestone in chemical physics and physical chemistry for biomedical applications. In this context, the role of incorporating different forms of porphyrins, their relationship with the final surface morphology, and their drug/gene loading efficiency were investigated to provide a predictable pattern in regard to the previous works. The conceptual phenomenon was optimized to increase the interactions between the biomolecules and the substrate by reaching the limit of detection to 10 pM for the Anti-cas9 protein, 20 pM for the single-stranded DNA (ssDNA), below 10 pM for the single guide RNA (sgRNA) and also around 10 nM for recombinant SARS-CoV-2 spike antigen. Also, the MTT assay showed acceptable relative cell viability of more than 85% in most cases, even by increasing the dose of the prepared nanostructures.

The objective of this study was to investigate the loading capacity and release profiles of curcumin (CUR), as a hydrophobic drug molecule, and doxorubicin hydrochloride (DOX), as a hydrophilic drug molecule, into hollow mesoporous silica nanoparticles (HMSNs) through a co-delivery system. The drug loading and release studies were conducted and analyzed by HPLC–UV. The hydrodynamic size and zeta potential of HMSNs were 206.8 nm and − 28.8 mV respectively. Drug loadings of DOX into HMSN-DOX NPs and HMSN-DOX-CUR NPs were 37.51 ± 2.07% and 18.57 ± 6.22% respectively, and the loading capacities of CUR in HMSN-CUR NPs and HMSN-DOX-CUR NPs were 61.57 ± 2.82% and 43.73 ± 8.3% respectively. The release study of DOX in phosphate buffer saline (PBS, pH = 7.4) showed that 10.36 ± 0.7% and 13.06 ± 0.26% of loaded DOX in HMSN-DOX NPs and HMSN-DOX-CUR NPs were released after 24 h, respectively, whereas 92.04 ± 3.89% and 95.53 ± 0.29% of the loaded CUR in HMSN-CUR NPs and HMSN-DOX-CUR NPs were released after 6 h in albumin 3%, pH = 7.4, respectively. The result of this study suggests that HMSNs can be used as a suitable candidate system for the delivery of hydrophilic drugs in cancer therapies, thanks to their ability to prevent premature drug release from NPs. On the other hand, the release study of CUR as a hydrophobic drug model suggests that the considered NPs may not be a suitable candidate for the delivery of such drugs in cancer therapies due to the rapid release of compounds in a simulated plasma model.

Gene therapy is regarded as a valuable strategy for efficient cancer treatment. However, the design of effective delivery systems that can deliver gene materials such as siRNA specifically to the tumour tissues plays a pivotal role in cancer therapy. For this reason, a targeted cationic liposome for melanoma treatment was developed. This system consists of cyclic RGD peptide conjugated to DSPE-PEG2000, cholesterol, DOTAP, and DSPC as cationic and neutral lipids, respectively. Cyclic RGD was selected based on speculation that cyclic RGD would effectively transport anti-signal transducer and activator of transcription 3 (STAT3) siRNA into melanoma cell via integrin receptors. The prepared liposomes provided excellent stability against electrolyte and serum nucleases. Targeted liposomes remarkably exhibited higher cellular internalisation in comparison with the non-targeted system in flow cytometry and confocal microscopy. Furthermore, incorporating peptide on the surface of liposomes resulted in considerably high cytotoxicity, a 2.1-times raise in apoptosis induction, and a significantly enhanced STAT3 gene suppression as compared with the corresponding non-targeted formulation on B16F10 murine melanoma cells. Whole-body imaging confirmed the more significant tumour accumulation of targeted liposomes in B16F10 melanoma xenograft tumour-bearing mice. Consequently, c-RGD peptide modified liposome suggests a promising option for specific siRNA delivery into melanoma cells.

Microvascular complications are among the major outcomes of patients with type II diabetes mellitus, which are the consequences of impaired physiological functioning of small blood vessels and angiogenic responses in these patients. Overproduction and accumulation of methylglyoxal (MGO), a highly reactive dicarbonyl byproduct of glycolysis pathway, has been acclaimed as the main inducer of impaired angiogenic responses and microvascular dysfunction in diabetic patients with uncontrolled hyperglycemia. Hence, an effective approach to overcome diabetes-associated microvascular complications is to neutralize the deleterious activity of enhanced the concentration of MGO in the body. Owing to the glycation inhibitory activity of

Enhanced understanding of bio-nano interaction requires recognition of hidden factors such as protein corona, a layer of adsorbed protein around nano-systems. This study compares the biological identity and fingerprint profile of adsorbed proteins on PLGA-based nanoparticles through nano-liquid chromatography-tandem mass spectrometry. The total proteins identified in the corona of nanoparticles (NPs) with different in size, charge and compositions were classified based on molecular mass, isoelectric point and protein function. A higher abundance of complement proteins was observed in modified NPs with an increased size, while NPs with a positive surface charge exhibited the minimum adsorption for immunoglobulin proteins. A correlation of dysopsonin/opsonin ratio was found with cellular uptake of NPs exposed to two positive and negative Fc receptor cell lines. Although the higher abundance of dysopsonins such as apolipoproteins may cover the active sites of opsonins causing a lower uptake, the correlation of adsorbed dysopsonin/opsonin proteins on the NPs surface has an opposite trend with the intensity of cell uptake. Despite the reduced uptake of corona-coated NPs in comparison with pristine NPs, the dysopsonin/opsonin ratio controlled by the physicochemistry properties of NPs could potentially be used to tune up the cellular delivery of polymeric NPs. (C) 2019 Elsevier Inc. All rights reserved.

Purpose This paper aims to simulate the steady laminar mixed convection incompressible viscous and electrically conducting hybrid nanofluid (CuO-Cu/blood) flow near the plane stagnation-point over a horizontal porous stretching sheet along with an external magnetic field and induced magnetic field effects that can be applicable in the biomedical fields like the flow dynamics of the micro-circulatory system and especially in drug delivery. Design/methodology/approach The basic partial differential equations (PDEs) are altered to a set of dimensionless ordinary differential equations (ODEs) with the help of suitable similarity variables which are then solved numerically using bvp4c scheme from MATLAB. Inasmuch as validation results have shown a good agreement with previous reports, the present novel mass-based algorithm can be used in this problem with great confidence. Governing parameters are both nanoparticle masses, base fluid mass, empirical shape factor of both nanoparticles, suction/injection parameter, magnetic parameter, reciprocal magnetic Prandtl number, Prandtl number, heat source parameter, mixed convection parameter, permeability parameter and frequency ratio. The effect of these parameters on the flow and heat transfer characteristics of the problem is discussed in detail. Findings It is shown that the use of CuO and Cu hybrid nanoparticles can reduce the hemodynamics effect of the capillary relative to pure blood case. Moreover, as the imposed magnetic field enhances, the velocity of the blood decreases. Besides, when the blade shapes for both nanoparticles are taken into account, the local heat transfer rate is maximum that is also compatible with experimental observations. Originality/value An innovative mass-based model of CuO-Cu/blood hybrid nanofluid has been applied. The novel attitude to one-phase hybrid nanofluid model corresponds to considering nanoparticles mass as well as base fluid mass to computing the solid equivalent volume fraction, the solid equivalent density and also solid equivalent specific heat.

Fulfilling the purpose of developing a NP with theragnostic capabilities, the current study describes the synthesis of an aptamer-functionalized PEG-coated SPION/mesoporous silica core-shell nanoparticle for concurrent cancer targeted therapy and magnetic resonance imaging. SPIONs were synthesized according to a thermal decomposition method and served as cores for SPION/mesoporous silica core/shell nanoparticles (MMSNs). Doxorubicin was then successfully loaded in MMSNs which were then coated with di-carboxylic acid functionalized polyethylene glycol (PEG-MMSNs). AS1411 aptamers were at the end covalently attached to NPs (APT-PEG-MMSNs). The mean diameter of synthesized NPs was about 89 nm and doxorubicin encapsulation efficacy was ≈67.47%. Results of MTT based cell cytotoxicity assay demonstrated a significantly higher toxicity profile for APT-PEG-MMSNs against MCF7 cells compared to non-decorated MMSNs, while no significant differences were spotted against NIH-3T3 cells. Meanwhile, formation of protein corona around APT-PEG-MMSNs in biological medium significantly attenuated observed cytotoxicity against MCF7 cell line. Examining NPs uptake by MCF7 cells using confocal laser scanning microscopy also confirmed superiority of APT-PEG-MMSNs over PEG-MMSNs. Finally, APT decorated NPs induced highest signal intensity reduction in T

Background: Curcumin, a bioactive component with multiple characteristics, has been shown to have many therapeutic effects. However, there are several limitations regarding the use of curcumin such as instability, low solubility, poor bioavailability, and rapid elimination. Different approaches have been used to solve these problems. Materials and methods: In this study, surface-modified nanosuspension (NS) is investigated as a novel brain delivery system. Two different methods were used for the preparation of nanosuspensions with two different stabilizers. The surface of the nanosuspensions was coated with D-α-tocopheryl polyethylene glycol 1,000 succinate (TPGS) and Tween 80 using physical adsorption. Curcumin NSs were prepared using two different top-down techniques by high-pressure homogenizer and probe sonicator. A validated sensitive and selective high-performance liquid chromatography method using fluorescence detection was used for the determination and quantification of curcumin. Pharmacokinetics and biodistribution of curcumin NSs and solutions after intravenous administration in rats were studied. Results: Higher levels of curcumin in the brain were detected when Tween 80-coated NS was used compared with the curcumin solution and TPGS coated NS (TPGS-NS) (P-value

Bio-nano interface investigation models are mainly based on the type of proteins present on corona, bio-nano interaction responses and the evaluation of final outcomes. Due to the extensive diversity in correlative models for investigation of nanoparticles biological responses, a comprehensive model considering different aspects of bio-nano interface from nanoparticles properties to protein corona fingerprints appeared to be essential and cannot be ignored. In order to minimize divergence in studies in the era of bio-nano interface and protein corona with following therapeutic implications, a useful investigation model on the basis of RADAR concept is suggested. The contents of RADAR concept consist of five modules: 1- Reshape of our strategy for synthesis of nanoparticles (NPs), 2- Application of NPs selected based on human fluid, 3- Delivery strategy of NPs selected based on target tissue, 4- Analysis of proteins present on corona using correct procedures and 5- Risk assessment and risk reduction upon the collection and analysis of results to increase drug delivery efficiency and drug efficacy. RADAR grouping strategy for revisiting protein corona phenomenon as a key of success will be discussed with respect to the current state of knowledge.

Overprescribing of antibiotics and injectable medicines is common in ambulatory care in many low- and middleincome countries. We evaluated the effects of three different interventions in improving physician prescribing. We conducted a four-armed randomized controlled trial with one-month and three- months follow-up. General physicians, pediatricians, and infectious disease specialists were included in this study if they had an outpatient office in Tehran, Iran. The study involved two behaviorally guided interventions: "new-design audit and feedback (NAF)"; "printed educational material (PEM)" and an existing intervention of "routinely conducted audit and feedback (RAF)". The theoretical framework underpinning the intervention was the theory of planned behavior. Main outcome measures were the percentage change in the proportion of prescriptions containing injectable dexamethasone; oral amoxicillin and cefixime. NAF reduced the proportion of prescriptions particularly those containing dexamethasone injectable and cefixime (1.64, 0.99 absolute percentage change, p = 0.006, p = 0.01 respectively). PEM reduced the proportion of prescriptions containing cefixime (0.93 absolute percentage change p = 0.04). Other primary outcomes had no significant differences. A secondary outcome measure showed overall prescribing of injectables also reduced (absolute risk reduction: 3%). Overally, the study provides strong evidence that using theoretical insights in the development of the intervention improved prescribing behavior that lasted at least three months after the intervention. The design, format, and presentation of messages in feedback forms significantly influence the impact of audit and feedback on physician prescribing. While the interventions were effective, the impacts on inappropriate prescribing were modest and limited. In settings with rampant problems of overprescribing, intensive interventions are required to substantially improve prescribing patterns. Graphical abstract Graphical abstract.

Lung cancer is the foremost reason of death from cancers with broad genetic and epigenetic diversity. Various strategies are clinically available for diagnosis and treatment of lung cancer. However, in many cases, the disease is diagnosed after malignancy that reduce the survival rate of lung cancer patients due to unsuccessful response to therapy. With the help of nanotechnology, various nanoparticulate systems including organic, inorganic, metallic, and polymeric nanoparticles have been developed for diagnosis and treatment of lung cancer. Each of these nanocarriers possess their own advantages and disadvantages. Combining the organic and inorganic components in a single hybrid nanosystem prepares a new generation of multifunctional nanoparticles with enhanced structural and biological properties. Such nanoparticles not only have beneficial features of all the bulk materials, but also can be tuned in terms of structural and functional moieties to provide carriers with improved diagnostic and therapeutic outcomes. Indeed, hybrid nanoparticles with the ability to incorporate multiple drugs, targeting agents, and photosensitive reagents opened new insights into developing more sensitive and specified systems for diagnosis and treatment of lung cancer compared with conventional nanocarriers. In this review, recent developments in designing different hybrid nanoparticles with diagnostic, therapeutic, and theranostic properties for lung cancer are explained in detail.

Recently, numerous bioconjugation procedures were developed to promote the pharmacokinetic and immunological properties of L-asparaginase (ASNase), an anti-leukemic enzyme. Here, compared with PEGylation, the influence of the protein conjugation with poly(HPMA) on enzyme stabilization was investigated. Poly(HPMA) synthesis was carried out via RAFT polymerization to obtain a well-defined polymer chain with pre-designed molecular weight (Mn = 5.5 kDa) and narrow polydispersity (PDI = 1.2). Poly(HPMA) was then activated with different coupling agents including carbonyldiimidazole, carboxydiimidazole and succinic anhydride, which were conjugated with the enzyme. SDS-PAGE analysis revealed that the highest conjugation degree was related to succinic anhydride. To determine the optimum bioconjugation condition, the impacts of succination degree and polymer : protein ratio were evaluated. Poly(HPMA)–ASNase at the succination ratio of 1.5 and the polymer : protein lysine molar ratio of 7 : 1, presented a conjugation degree and retained an enzyme activity of 42.4% and 47.8%, respectively. The kinetic parameters were also calculated, indicating no significant difference between poly(HPMA) and commercially available PEG conjugate. The results also showed that poly(HPMA) conjugates had superior stability at different pH and temperature and were resistant to proteolysis and freeze–thaw when compared with PEGylated or native ASNase. All in all, the results clearly show that the novel poly(HPMA) bioconjugation strategy has potential for biomedical applications of ASNase.

Although stem cell therapy is a major area of interest in tissue engineering, providing proper oxygen tension, good viability, and cell differentiation remain challenges in tissue-engineered scaffolds. In this study, an osteogenic scaffold was fabricated using the 3D bio-printing technique. The bio-ink contained alginate hydrogel, encapsulated human bone marrow-derived mesenchymal stem cells (hBM-MSCs), calcium peroxide nanoparticles (CPO NPs) as an oxygen generating biomaterial, and bone morphogenic protein-2 nanoparticles (BMP2 NPs) as an osteoinductive growth factor. CPO NPs were synthesized with the hydrolysis-precipitation method, and their concentrations in the bio-ink were optimized. Scaffolds containing CPO 3% (w/w) were preferred, because they generated sufficient oxygen gas for 20 days, increased mechanical strength after 20 days, and had sufficient stability. The CPO NPs effect on the viability of embedded hBM-MSCs under hypoxic conditions was analyzed. Live/Dead staining results represented a 22% improvement in CPO 3% scaffold viability on day 7. Therefore, CPO NPs constituted a promising survival factor. BMP2 NPs were prepared with the double emulsification technique. The incorporation of both BMP2 and CPO NPs resulted in the upregulation of Runt-related transcription factor 2, Collagen type I alpha 1, and the osteocalcin genes compared to internal references in osteogenic media. Overall, the proposed 3D bio-printed osteogenic scaffold in this study has moved scientific research one step forward toward successful stem cell therapy and helped improve host tissue healing by biological activity enhancement, especially for low oxygen pressure tissues.

SN38 is the active metabolite of irinotecan with 1000-fold greater cytotoxicity compared to the parent drug. Despite the potential, its application as a drug is still seriously limited due to its stability concerns and low solubility in acceptable pharmaceutical solvents. To address these drawbacks here nanostructured lipid carrier (NLC) containing SN38 was prepared and its cytotoxicity against U87MG glioblastoma cell line was investigated. The formulations were prepared using hot ultrasonication and solvent evaporation/emulsification methods. NLCs with a mean size of 140 nm and particle size distribution (PDI) of 0.25 were obtained. The average loading efficiency was 9.5% and its entrapment efficiency was 81%. In order to obtain an accurate determination of released amount of SN38 a novel medium and extraction method was designed, which lead to an appropriate in vitro release profile of the drug from the prepared NLCs. The MTT test results revealed the significant higher cytotoxicity of NLCs on U87MG human glioblastoma cell line compared with the free drug. The confocal microscopy images confirmed the proper penetration of the nanostructures into the cells within the first 4 h. Consequently, the results indicated promising potentials of the prepared NLCs as a novel treatment for glioblastoma.

Indirubin can be applied as an anti-cancer drug for inhibition of brain tumors. However, its performance is reduced due to hydrophobicity. In this study, we synthesized cationic human serum albumin (CHSA) nanoparticle by a new hybrid approach for improvement the surface chemistry of albumin and investigate the amount of indirubin loaded CHSA nanoparticle. In this study, the generated mechanical force from a high-pressure homogenizer (HPH) was used to make nanoparticles with a certain size with narrow polydispersity. The results indicated that the size of indirubin loaded CHSA nanoparticles were 130 nm and their zeta potential were +9. Besides, the encapsulation efficiency and drug loading capacity were found to be 85% and 5.8 %, respectively. To the best to our knowledge, this is the first time that indirubin has been used in albumin nanoparticles. In this study, indirubin loaded CHSA nanoparticles was shown can be a potential candidate for drug delivery in the treatment of glioblastoma. Moreover, the cationized form allows the chemical agent to be transmitted to the brain.

The novel coronavirus pandemic has rapidly spread around the world since December 2019. Various techniques have been applied in identification of SARS-CoV-2 or COVID-19 infection including computed tomography imaging, whole genome sequencing, and molecular methods such as reverse transcription polymerase chain reaction (RT-PCR). This review article discusses the diagnostic methods currently being deployed for SARS-CoV-2 identification including optical biosensors and point-of-care diagnostics that are on the horizon. These innovative technologies may provide a more accurate, sensitive and rapid diagnosis of SARS-CoV-2 to manage the present novel coronavirus outbreak, and could be beneficial in preventing any future epidemics. Furthermore, the use of green synthesized nanomaterials in the optical biosensor devices could leads to sustainable and environmentally-friendly approaches for this crisis., Graphical abstract Image

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

In this work, three different samples of molybdenum disulfide (MoS2) nanoflakes, carbon nanoparticles and molybdenum disulfide/carbon (MoS2/C) nanocomposite were synthesized by one step hydrothermal method. The structural and optical properties of the samples were characterized by X-ray diffraction, transmission electron microscopy, energy-dispersive X-ray spectroscopy mapping, Raman, Fourier transform infrared, and Ultraviolet–visible spectroscopies. Photothermal experiment was also performed for these three samples after 10 min laser irradiation (808 nm, 1 W/cm2 power density) for 600 s. The photothermal results of samples indicated that the effect of the carbon content in nanocomposite has produced higher heat in MoS2/C sample than other samples. Then, in order to load drug, a potent anti-cancer drug doxorubicin (DOX) was loaded in MoS2/C-PEG up to 21% and the release of drug was evaluated by irradiation of near infrared (NIR) light. In the NIR irradiation, the amount of DOX released in pH 5 from nanocomposite was higher than pH 7.4. The drug release was found to enhance with NIR laser irradiation, which shows that the composites respond by pH or NIR irradiation for DOX release, so the release process could be controllable. The results of MTT assay showed that carbon nanoparticles, MoS2, and MoS2/C samples possess negligible cytotoxicity without irradiation NIR laser. Using NIR irradiation, the relative viabilities of Hela cells decreased when the concentration of samples increased. For DOX-loaded MoS2/C-PEG, results revealed that by increasing DOX loading the cell viability decreases especially under the NIR irradiation.

Alzheimer's disease (AD), the most common neurodegenerative disorder, is characterized by progressive cognitive impairment and memory loss. The mammalian target of rapamycin (mTOR) signaling pathway could regulate learning and memory. The effect of rapamycin (Rapa) on mTOR activity could slow or prevent the progression of AD by affecting various essential cellular processes. Previously, we prepared transferrin (Tf) decorated-nanostructured lipid carriers (NLCs) for rapamycin (150 ± 9 nm) to protect the drug from chemical and enzymatic degradation and for brain targeted delivery of rapamycin. Herein, the effect of Tf-NLCs compared to untargeted anionic-NLCs and free rapamycin, were studied in amyloid beta (Aβ) induced rat model of AD. Behavioral test revealed that the Rapa Tf-NLCs were able to significantly improve the impaired spatial memory induced by Aβ. Histopathological studies of hippocampus also showed neural survival in Rapa Tf-NLCs treated group. The immunosuppressive, and delayed wound healing adverse effects in the rapamycin solution treated group were abolished by incorporating the drug into NLCs. The Aβ induced oxidative stress was also reduced by Rapa Tf-NLCs. Molecular studies on the level of Aβ, autophagy (LC3) and apoptotic (caspase-3) markers, and mTOR activity revealed that the Rapa Tf-NLCs decreased the Aβ level and suppressed the toxic effects of Aβ plaques by modulating the mTOR activity and autophagy, and decreasing the apoptosis level. As a conclusion, the designed Tf-NLCs could be an appropriate and a safe brain delivery system for rapamycin and make this drug more efficient in AD for improving memory and neuroprotection.

Decorating photocatalysts with noble metal nanoparticles (e.g., Pt) often increases the catalysts&rsquo, photocatalytic activity and biomedical properties. Here, a simple and inexpensive method has been developed to prepare a Pt-Ag3PO4/CdS/chitosan composite, which was characterized and used for the visible light-induced photocatalytic and antibacterial studies. This synthesized composite showed superior photocatalytic activity for methylene blue degradation as a hazardous pollutant (the maximum dye degradation was observed in 90 min of treatment) and killing of Gram positive bacterial (Staphylococcus aureus and Bacillus cereus) as well as Gram negative bacteria (Klebsiella pneumoniae, Salmonella typhimurium, Escherichia coli, and Pseudomonas aeruginosa) under visible light irradiation. The antibacterial activity of CdS, CdS/Ag3PO4, and Pt-Ag3PO4/CdS/chitosan against E. coli, Pseudomonas aeruginosa, Salmonella typhimurium, Klebsiella pneumoniae, Staphylococcus aureus, and Bacillus cereus showed the zone of inhibition (mm) under visible light and under dark conditions at a concentration of 20 &micro, g mL&minus, 1. Furthermore, the cell viability of the CdS/chitosan, Ag3PO4, Ag3PO4/CdS/chitosan, and Pt-Ag3PO4/CdS/chitosan were investigated on the human embryonic kidney 293 cells (HEK-293), Henrietta Lacks (HeLa), human liver cancer cell line (HepG2), and pheochromocytoma (PC12) cell lines. In addition, the results indicated that the photodegradation rate for Pt-Ag3PO4/CdS/chitosan is 3.53 times higher than that of CdS and 1.73 times higher than that of the CdS/Ag3PO4 composite. Moreover, Pt-Ag3PO4/CdS/chitosan with an optimal amount of CdS killed large areas of different bacteria and different cells separately in a shorter time period under visible-light irradiation, which shows significantly higher efficiency than pure CdS and other CdS/Ag3PO4 composites. The superb performances of this composite are attributed to its privileged properties, such as retarded recombination of photoinduced electron/hole pairs and a large specific surface area, making Pt-Ag3PO4/CdS/chitosan a valuable composite that can be deployed for a range of important applications, such as visible light-induced photocatalysis and antibacterial activity.

Aims Exosomes hold great promise as bio-inspired delivery vehicles. Mesenchymal stem cells (MSCs) are recognized for their potential to yield huge quantities of exosomes. We aimed to investigate the potential use of modified exosomes derived from genetically modified dental pulp MSCs (DPSCs) as a carrier to deliver tumor suppressor miR-34a to repress proliferation of breast carcinoma cells. Materials and methods miR-34a-overexpressing DPSCs were prepared using XMIRXpress-34a lentivectors. The anticancer effects of the miR-34a-loaded exosomes were evaluated on breast carcinoma cells through apoptosis, migration, and invasion assays. Given the structural similarity between exosomes and liposomes, we compared the exosome-mediated miRNA delivery efficiency with that of liposomes. Key findings Our data demonstrated that genetically modified DPSCs were capable of secretion of exosomes enriched with therapeutic miRNAs and presented the feasibility of application of exosome-based vehicle for gene delivery. Significance We showed the potential of MSC-derived exosomes as a tool for delivery of miRNAs in vitro. Nevertheless, optimizing gene-loading approaches is required before exosomes can be intended as a miRNA carrier for therapeutic applications.

Introduction: Recent studies showed that rapamycin, as a mammalian target of rapamycin (mTOR) inhibitor, could have beneficial therapeutic effects for the central nervous system (CNS) related diseases. However, the immunosuppressive effect of rapamycin as an adverse effect, the low water solubility, and the rapid in vivo degradation along with the blood-brain barrier-related challenges restricted the clinical use of this drug for brain diseases. To overcome these drawbacks, a transferrin (Tf) decorated nanostructured lipid carrier (NLC) containing rapamycin was designed and developed. Methods: Rapamycin-loaded cationic and bare NLCs were prepared using solvent diffusion and sonication method and well characterized. The optimum cationic NLCs were physically decorated with Tf. For in vitro study, the MTT assay and intracellular uptake of nanoparticles on U-87 MG glioblastoma cells were assessed. The animal biodistribution of nanoparticles was evaluated by fluorescent optical imaging. Finally, the in vivo effect of NLCs on the immune system was also studied. Results: Spherical NLCs with small particle sizes ranging from 120 to 150 nm and high entrapment efficiency of more than 90%, showed ≥80% cell viability. More importantly, Tf-decorated NLCs in comparison with bare NLCs, showed a significantly higher cellular uptake (97% vs 60%) after 2 hours incubation and further an appropriate brain accumulation with lower uptake in untargeted tissue in mice. Surprisingly, rapamycin-loaded NLCs exhibited no immunosuppressive effect. Conclusion: Our findings proposed that the designed Tf-decorated NLCs could be considered as a safe and efficient carrier for targeted brain delivery of rapamycin which may have an important value in the clinic for the treatment of neurological disorders.

Retinoblastoma (Rb) is the most common intraocular malignancy in children that accounts for approximately 4% of all pediatric malignancies. Since chemotherapy is a widely practiced treatment for Rb, there is a growing interest in developing new and effective drugs to overcome systemic and local side effects of chemotherapy to improve the quality of life and increase the chances of survival. This study sought to fabricate thiolated chitosan nanoparticles containing topotecan (TPH-TCs-NPs) with a view of enhancing drug loading and release control. This research was also designed to assess the ability of TPH-TCs-NPs to improve cell association, increase treatment efficacy in retinoblastoma cells and xenograft-rat-model of retinoblastoma, and overcome current topotecan hydrochloride (TPH) intravitreal administration challenges, including stability loss and poor cellular uptake. Modified ionic gelation method was optimized to fabricate TPH-TCs-NPs and TPH-TMC-NPs (N-trimethyl chitosan nanoparticles containing TPH). We characterized the NPs and quantified topotecan loading and release against a free TPH standard. The efficacy of TPH-NPs was quantified in human retinoblastoma cells (Y79) by XTT and flow cytometry measurement. In addition, Y79 cells were injected intravitreally in both eyes of immunodeficient wistar albino rats to create a xenograft-rat-model to compare the antitumor effectiveness of TPH-NPs and TPH by intravitreal administration. TPH-NPs complexation was confirmed by EDX, FTIR, and DSC techniques. TPH-TCs-NPs and TPH-TMC-NPs had high encapsulation efficiency (85.23 ± 2 and 73.34 ± 2% respectively). TPH-TCs-NPs showed a mean diameter, polidispersity index, and zeta potential of 25±2 nm, 0.21 ± 0.03 and +12 ± 2 mV, respectively. As a function of dose, TCs and TMC NPs were more efficacious than free topotecan (IC50s 53.17 and 85.88 nM, relative to 138.30 nM respectively, P = 0.012). Kruskal-Wallis test showed a statistically significant difference between the groups. Additionally, a significant difference between the tumor control and TPH-TCs-NPs treated group in xenograft-rat-model ( Range of P-value: 0.026 to 0.035) was shown by Bonferroni post hoc test. The current investigation demonstrated enhanced efficacy and association of TPH-TCs-NPs relative to free TPH in retinoblastoma cells and tumor in vitro and in vivo.