Photo-responsive nanoparticles for β-lapachone delivery in vitro

We reported a one-step encapsulation of indocyanine green (ICG) in ZIF-8 nanoparticles (NPs). The as-prepared ICG@ZIF-8 NPs possess an absorption band in the near infrared region and have the good photothermal conversion efficiency.     

Multifunctional hybrid nanoconjugates for efficient in vivo delivery of immunomodulating oligonucleotides and enhanced antitumor immunity

A winning combination: Multifunctional hybrid nanoconjugates (HNCs) based on polymer nanoparticles containing quantum dots (QDs) conjugated with CpG oligonucleotides (as a ligand for TLR9) and STAT3 siRNAs (to suppress the immune response) have been synthesized. These HNCs were shown to synergistically enhance the antitumor immune response in dendritic cells and in tumor-bearing mice.     

In vitro and in vivo evaluation of β-cyclodextrin-based nanosponges of telmisartan

Telmisartan (TEL) is a BCS Class II drug having dissolution rate limited bioavailability. The aim of work was to enhance the solubility of TEL so that bioavailability problems are solved. β-Cyclodextrin (β-CD) based nanosponges (NSs) were formed by cross-linking β-CD with carbonate bonds, which were porous as well as nanosized. Drug was incorporated by solvent evaporation method. The effect of ternary component alkalizer (NaHCO₃) on solubility of TEL was studied. In order to find out the solubilization efficiency of NS, phase solubility study was carried out. Saturation solubility and in vitro dissolution study of β-CD complex of TEL was compared with plain TEL and NS complexes of TEL. The NS and NS complexes of TEL were characterized by differential scanning calorimetry, powder X-ray diffraction, Fourier transform infrared spectroscopy, nuclear magnetic resonance and scanning electron microscope. It was found that solubility of TEL was increased by 8.53-fold in distilled water; 3.35-fold in 0.1 N HCl and 4.66-fold in phosphate buffer pH 6.8 by incorporating NaHCO₃ in drug–NS complex than TEL. It was found that the NaHCO₃ in NS based complex synergistically enhanced dissolution of TEL by modulating microenvironmental pH and by changing amorphization of the drug. The highest solubility and in vitro drug release was observed in inclusion complex prepared from NS and NaHCO₃. An increase of 54.4 % in AUC was seen in case the ternary NS complex whereas β-CD ternary complex exhibited an increase of 79.65 %.     

Functional mesoporous silica nanoparticles for photothermal-controlled drug delivery in vivo

Release me! A new class of photothermal-responsive [2]rotaxane-appended mesoporous silica nanoparticles (MSNPs) was developed. Remote-controlled movement of the α-cyclodextrin ring?(green) upon trans-cis isomerization of the azobenzene axle?(red) enables the loading and release of drugs on demand. Curcumin-loaded MSNPs were shown to release curcumin into zebrafish larvae upon treatment with visible light or heat.     

In vitro gene delivery mediated by lactosylated dendrimer (generation 3, G3)/��-cyclodextrin conjugates into hepatocytes

The purpose of this study is to evaluate in vitro gene delivery efficiency of polyamidoamine (PAMAM) starburst dendrimer (generation 3, G3) conjugates with ??-cyclodextrin (??-CDE (G3)) bearing lactose (Lac-??-CDE) with various degrees of substitution of the lactose moiety (DSL) as a novel hepatocyte-selective carrier. Lac-??-CDE (G3, DSL 1.2) was found to have much higher gene transfer activity than ??-CDE (G3), Lac-??-CDE (G2, DSL 2.6) and Lac-??-CDEs (G3, DSL 2.6, 4.1 and 6.1) in HepG2 cells, which are dependent on the expression of cell-surface asialoglycoprotein receptor (ASGP-R). Lac-??-CDE (G3, DSL 1.2) provided negligible cytotoxicity up to a charge ratio of 100 (carrier/pDNA) in HepG2 cells. These results suggest the potential use of Lac-??-CDE (G3, DSL 1.2) as a non-viral vector for gene delivery toward hepatocytes.     

Investigating the potential of tetrahydropyridinyl chalcones as useful agents against breast carcinoma: An in vitro and in vivo study

N-Benzyltetrahydropyridinyl-4,6-dimethoxy phenyl-substituted 2′-hydroxychalcones SJC1–15 were synthesized using Claisen–Schmidt condensation, their structures confirmed by spectral analysis, and their anticancer activity evaluated. To support their biological activity, physicochemical parameters such as lipophilicity and oxidation potential were determined. To assess their relative cytotoxicity, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed using MCF-7, T-47D, MDA MB-231, HepG₂, and Vero cell lines. The cytotoxicity of the chalcones was found to vary with the nature of the ring B substituents. The lipophilicity of the cytotoxic compounds expressed in terms of distribution coefficient was found to lie in the range of 2.4–4.2. Further evaluation of their antioxidant potential revealed antioxidant activity by 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical scavenging assay and irreversible electrochemical reaction with oxidation potential in the range of 0.879–1.048 V. Of the 15 chalcones, SJC4, 5, 9 were selected for further in vitro studies using MCF-7. The compounds exhibited significant apoptotic effect and caused cell cycle arrest at G0/G1 and G2/M phase. Among them, two of the O-alkylated chalcones (SJC5, 9) showing promising activity against hormone-responsive breast cancer cells were evaluated for their in vivo anticancer activity using 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumor model. Three-week treatment with the test compounds at oral dosage of 100 mg kg^?1 per day significantly improved elevated tumor parameters compared with tumor control. Treatment with chalcone SJC5 (a 2,4,5-trimethoxy derivative) exhibited anticancer effects similar to those of doxorubicin (2 mg kg^?1 per week, i.p.) and was free from toxic effects observed with doxorubicin treatment.     

Bioevaluation of 99mTc(CO)3–Guanine in vitro and in vivo

The aim of this study is to examine biological behaviour of radiolabeled guanine with [Tc(CO)₃]⁺ core in vitro and in vivo. In vitro biological behavior of ^99mTc(CO)₃–Gua was evaluated on Lung (A-549), Breast (MCF-7), Colonic (Caco) carcinoma cell lines and normal human bronchial epithelial (NHBE). ^99mTc(CO)₃–Gua compound showed high uptake on A-549 cell line when compared to NHBE cell line. Biodistribution characteristics of ^99mTc(CO)₃–Gua was evaluated using New Zeland Rabbits. Scintigraphic results showed that a high level of radioactivity was observed in the lungs and liver shortly after administration of the ^99mTc(CO)₃–Gua and excretion takes place via both renal and hepatobiliary route. It was concluded that ^99mTc(CO)₃–Gua could be used as a nucleotide radiopharmaceutical for imaging purposes.     

Imageable antigen-presenting gold nanoparticle vaccines for effective cancer immunotherapy in vivo

Delivery tracking: Goldnanoparticles (AuNPs) were functionalized with a red fluorescent protein (RFP, pink shapes in picture) as model antigen and an oligonucleotide (CpG) that stimulates the immune response. These functionalized AuNPs were used as cancer vaccines in a tumor model, where they enabled efficient delivery of an antigen to target sites, tracking of the vaccines using noninvasive clinical imaging, and cancer prevention and therapy.     

The screening and evaluating of chitosan/β-cyclodextrin nanoparticles for effective delivery mitoxantrone hydrochloride

The complex of chitosan and β-cyclodextrin (CS-CMβ-CD) has been widely used as drug carrier because it binds the advantages of GCH and β-CDs. But further investigation is still needed to improve their delivery performance before CS-β-CD derivatives can be used as clinical cancer-drug carriers. The aim of the study is to screen suitable carriers of the deviants of chitosan and β-cyclodextrin by evaluating the delivery performance of several carriers towards anticancer drugs. Three kinds of GCS _n -CM _m β-CD polymers made of different amount of glycol chitosan (GCS) and carboxymethyl-β-cyclodextrin (CMβ-CD) were synthesized and GCS_7.5-CM_3-7β-CD was chosen to deliver the drugs due to its better properties. GCS_7.5-CM_3-7β-CD polymers have better cell adhesion performance than GCS, help to directional drug delivery. Then, mitoxantrone hydrochloride (MAH) was used as a model drug to evaluate the loading and releasing properties of GCS_7.5-CM_3-7β-CD polymers. GCS_7.5-CM_3-7β-CD polymers could encapsulate MAH with higher loading efficiency and provide pH sensitive MAH release. The amount of MAH released in acidic medium (pH 5.0) was greater than that in weakly basic medium (pH 7.4). The MAH-loaded nanoparticles shows similar inhibition ability as free MAH to HCT116 cell lines, indicate that MAH can be release from the carrier and kill the cancer cells. In addition, the blank GCS_7.5-CM_3-7β-CD nanoparticles show good biocompatibility to the cell. That is to say, GCS_7.5-CM_3-7β-CD polymers not only have the ability to targeting drug delivery but also can realize pH sensitive release, which make them perspective in cancer pharmaceutical application.     

An NIR Fluorescence Turn-on and MRl Bimodal Probe for Concurrent Real-time in vivo Sensing and Labeling of β-Galactosidase

To realize sensing and labeling biomarkers is quite challenging in terms of designing multimodal imaging probes. In this study, we developed a novel β-galactosidase (β-gal) activated bimodal imaging probe that combines near-infrared (NIR) fluorescence and magnetic resonance imaging (MRI) to enable real-time visualization of activity in living organisms. Upon β-gal activation, Gal-Cy-Gd-1 exhibits a remarkable 42-fold increase in NIR fluorescence intensity at 717 nm, allowing covalent labeling of adjacent target enzymes or proteins and avoiding molecular escape to promote probe accumulation at the tumor site. This fluorescence reaction enhances the longitudinal relaxivity by approximately 1.9 times, facilitating high-resolution MRI. The unique features of Gal-Cy-Gd-1 enable real-time and precise visualization of β-gal activity in live tumor cells and mice. The probe's utilization aids in identifying in situ ovarian tumors, offering valuable assistance in the precise removal of tumor tissue during surgical procedures in mice. The fusion of NIR fluorescence and MRI activation through self-immobilizing target enzymes or proteins provides a robust approach for visualizing β-gal activity. Moreover, this approach sets the groundwork for developing other activatable bimodal probes, allowing real-time in vivo imaging of enzyme activity and localization.     

¹¹C-labeled analogs of indomethacin esters and amides for brain cyclooxygenase-2 imaging: radiosynthesis, in vitro evaluation and in vivo characteristics in mice

There is great potential in the use of positron emission tomography (PET) and suitable radiotracers for the study of cyclooxygenase type 2 (COX-2) enzyme in living subjects. In the present study, we prepared and evaluated five 11C-labeled ester and amide analogs derived from indomethacin as potential PET imaging agents for the in vivo visualization of the brain COX-2 enzyme. Five 11C-labeled COX-2 inhibitors, with different lipophilicities and moderate COX-2 inhibitory activity, were prepared by treatment of the corresponding O-desmethyl precursors with [11C]methyl triflate and purified by HPLC (radiochemical yields of 55-71%, radiochemical purity of >93%, and the specific activities of 22-331 GBq/μmol). In mice, radioactivity in the brain for all radiotracers was low, with very low brain-to-blood ratios. A clear inverse relationship was observed between brain uptake at 1 min postinjection and the lipophilicity (experimental log P?.?) of the studied 11C-radiotracers. Pretreatment of mice with cyclosporine A to block P-glycoproteins caused a significant increase in brain uptake of radioactivity following injection of the 11C-radiotracer compared to control. HPLC analysis showed that each radiotracer was rapidly metabolized, and a few metabolites, which were more polar than the original radiotracers, were found in both plasma and brain. No specific binding of the tracers towards the COX-2 enzyme in the brain was clearly revealed by in vivo blocking study. Further structural refinement of the tracer agent is necessary for better enhancement of brain uptake and for sufficient metabolic stability.     

Phytochemical and in vitro screening of some Ficus and Morus spp. for hypolipidaemic and antioxidant activities and in vivo assessment of Ficus mysorensis (Roth)

Phytochemical screening of air-dried leaves and fruit juice of certain Ficus and Morus spp. have been studied. In an in?vitro study, the ethanol and hexane extracts of the investigated plants were evaluated against hyperlipidaemia by estimating the rate limiting enzyme of cholesterol biothenysis; β-hydroxy-β-methylglutaryl coenzyme A reductase (HMG-CoA reductase). The antioxidant activity was evaluated by reduction of DPPH(-) free radical. Extra phytochemical screening of Ficus extracts was undertaken, which recorded potent hypolipidaemic and antioxidant activities. The more pronounced extract, Ficus mysorensis (hexane extract), was evaluated in?vivo by estimation of the lipid profile and certain antioxidant parameters in hypercholesterolemic rats. The hexane fraction was chromatographed and six isolated compounds were identified. Furthermore, its saponifiable fraction was identified by a MS/MS technique. In conclusion, F. mysorensis recorded hypolipidaemic and antioxidant effects. Detailed studies of the isolated compounds must be undertaken for an evaluation against hypercholesterolemia and free radical elevation.     

In vivo and in vitro emergence of simultaneous resistance to both β-lactam and aminoglycoside antibiotics in a strain of Serratia marcescens

In a patient with Serratia marcescens bacteraemia, a variant resistant to cefotaxime and amikacin was isolated in a blood culture under combined treatment with cefotaxime and amikacin. In addition, in vitro selection on cefotaxime and/or amikacin yielded resistant mutants from the sensitive parent strain. These mutants displayed the same type of cross-resistance as the clinical strain to all β-lactam and aminoglycoside antibiotics. The mechanisms for this resistance was a decrease in the permeability of the cell. To our knowledge, the isolation of such strains from blood cultures and the mechanism responsible for this ⪡ broad-spectrum resistance ⪢ have not been previously described.