Biocompatible polymer-coated magneto-fluorescent super nanoparticles for the homing of mesenchymal stem cells.

Stem cell plays an important role in the clinical field. However, the effective delivery of stem cells to the targeted site relies on the efficient homing of the cells to the site of injury. In view of that, fluorescent magnetic nanoparticles stick out due to their wide range of enabling functions including cellular homing and tracking. The present study unravels the synthesis of polymer-coated biocompatible and fluorescent magnetic nanoparticles (FMNPs) by a single-step hydrothermal synthesis method. Importantly, the facile method developed the biological super nanoparticles consisting of the magnetic core, which is surrounded by the fluorescent nanodot-decorated polymeric shell. The synthesized particles showed an amorphous nature, and superparamagnetic properties, with efficient fluorescence properties of emission at the blue range (Ì´ 410 nm). The FMNP labeling showed the mesenchymal stem cell (MSC) homing to the desired site in the presence of an external magnetic field. The in-house synthesized nanoparticles showed significant cytocompatibility and hemocompatibility in vitro as well as in vivo conditions owing to their surface coating. This unprecedented work advances the efficient internalization of FMNPs in MSCs and their enhanced migration potential provides a breakthrough in stem cell delivery for therapeutic applications. STATEMENT OF SIGNIFICANCE: The bi-modal fluorescent magnetic nanoparticles hold a promising role in the biomedical field for mesenchymal stem cell homing and tracking. Hence, in this study, for the first time, we have synthesized the fluorescent magnetic nanoparticle with polymer coating via an easy single-step method. The nanoparticle with a polymer coat enhanced the biocompatibility and effortless internalization of the nanoparticle into mesenchymal stem cells without hampering the native stem cell properties. Furthermore, the enhanced migration potential of such magnetized stem cells and their homing at the target site by applying an external magnetic field opened up avenues for the smart delivery of mesenchymal stem cells at complex sites such as retina for the tissue regeneration.

Synthon Approach in Crystal Engineering to Modulate Physicochemical Properties in Organic Salts of Chlorpropamide.

The formulation of drug with improved bioavailability is always challenging and indispensable in the field of pharmaceutics. The control of intermolecular interactions via crystal engineering approach and solid-state molecular recognition results in the formation of active drug molecules with modulated pharmacological benefits. Therefore, with the aim to improve the solubility and dissolution rate of the drug chlorpropamide (CPA), the mechanochemical liquid-assisted grinding (LAG) of the drug with several pharmaceutically accepted excipients was performed. This contributed to the discovery of six novel solid phases, namely salts, salt cocrystals and salt cocrystal hydrate─the salt of CPA with 3, 4-diaminopyridine (DAP); salt and salt cocrystal (SC) polymorph (Z″=3) with 1, 4-diazabicyclo [2.2.2] octane (DABCO); a salt, SC polymorph (Z″=9), and a SC hydrate (Z″=9) with piperazine (PIP). The formation of these salts and salt cocrystals are mainly guided by the strong hydrogen bonds with tunable strength having high electrostatic contribution. This attractive interaction brings the donor and the acceptor atoms close to each other for a facile proton transfer. Furthermore, the conformational constraints on the drug molecules, provided by the excipients via strong and directional hydrogen bonds, are quite impressive as this leads to the identification and characterization of "new conformational isomers" for the CPA molecules. The new crystalline phases exhibit enhanced intrinsic dissolution rate in comparison to that of the pure drug, the magnitude being 7, 131, and 120 folds for CPADAP, CPADABCO_II, and CPAPIP_III, respectively. Furthermore, it is interesting to note that the order of solubility is enhanced by 2.7-, 3-, and 7-fold, respectively, for the abovementioned salts. This also mirrors the trends in the magnitude of the binding energy, the higher magnitude being reflected in the lower solubility. Additionally, the in vivo experiments performed in SD rats results in the enhancement of the magnitude of the pharmacokinetic properties, when compared to the pristine drug. The concentration of the drug in CPADABCO_II and CPAPIP_III formulations exhibits 6- and 4-fold increments, respectively. Indeed, these results corroborate to the trends observed in the structural characterization, intermolecular energy calculations, solubility, and in vitro dissolution assessments.

Genetic Analysis for Resistance to Sclerotinia Stem Rot, Yield and Its Component Traits in Indian Mustard [Brassica juncea (L.) Czern & Coss.].

Understanding the mode of gene action that controls seed yield and Sclerotinia stem rot resistance in Indian mustard is critical for boosting yield potential. In a line × tester mating design, ten susceptible lines and four resistant testers were used to conduct genetic analysis. The significance of general combining ability (GCA) and specific combining ability (SCA) variances revealed that both additive and non-additive gene actions were involved in the inheritance of Sclerotinia stem rot resistance and yield attributing traits. In addition to 1000-seed weight and number of primary and secondary branches/plant, the genotypes RH 1569 (line) and DRMR 2035 (tester) appeared to be the strongest general combiners for Sclerotinia stem rot resistance. RH 1657 × EC 597317 was the only cross among several that demonstrated a significant desired SCA value for Sclerotinia rot resistance. Regarding SCA effects for yield and component traits, the cross RH 1658 × EC 597328 performed best, with a non-significant but acceptable negative SCA effect for resistance. DRMR 2035, RH 1222-28, RH 1569, RH 1599-41, RH 1657, RH 1658, and EC 597328 are promising genotypes to use as parents in future heterosis breeding and for obtaining populations with high yield potential and greater resistance to Sclerotinia stem rot disease in Indian mustard, based on GCA effects of parents, per se performance, and SCA effects of hybrids. Days to 50% flowering, number of primary branches/plant, main shoot length, and 1000-seed weight all had a high genotypic coefficient of variability (GCV), broad-sense heritability (h2bs), and genetic advance as percent of the mean (GAM) values, as well as significant and desirable correlations and direct effects on seed yield. As a result, these traits have been recognized as the most critical selection criterion for Indian mustard breeding programs.

Rapid tumor inhibition via magnetic hyperthermia regulated by caspase 3 with time-dependent clearance of iron oxide nanoparticles.

Among conventional cancer therapies, radio-frequency magnetic hyperthermia (MHT) has widely been investigated for use with magnetic nanoparticles (MNPs). However, the majority of in vivo biodistribution studies have tested very low MNP dosages (equivalent to magnetic resonance imaging (MRI) applications) to check for clearance rate; which is far below the clinical dose of MHT. Due to this poor validation in preclinical scenarios, quite a few MNPs already in clinical use were later discontinued, on grounds of unexpected clinical outcomes in terms of inflammation, and prolonged clearance in vivo. By exploiting an economical method of synthesis, we have developed chitosan-coated Fe3O4 nanoparticles with high heating efficiency performance. Their anti-tumor response was evaluated in an ectopic tumor model of C6 glioblastoma by MHT. The intratumoral injection of MNPs on days 1 and 7 resulted in rapid tumor inhibition rate of 69.4% within 8 days, with complete inhibition within 32 days, and no recurrence recorded over a 5-month follow-up. Notably, the MNP-mediated MHT therapy achieved the highest degree of therapeutic efficacy required for complete tumor ablation by combining controlled temperature range (<44 °C), reduced MNP dosage; much lower than in most reported studies, and AMF parameters (time of exposure and frequency) within the clinical safety limit. Periodic body weight measurements confirmed negligible adverse side effects in rats. The anti-tumor activity was validated by severe apoptosis (TUNEL, cleaved Caspase-3), reduced proliferation (Ki 67) and disrupted vasculature (CD 31) in the Fe3O4-MHT-treated group. Real-time gene expression of pro-inflammatory cytokines (IL-6, TNF-α, IL-1α, IL-1ß) confirmed the intratumoral activation of IL-6, suggesting the role of immunomodulation in triggering the adaptive immune response for faster tumor regression in the treated group. In addition, the biodistribution and clearance rate of MNPs monitored using ICP-OES confirmed their time-dependent biodegradation via excretion (urine, feces), phagocytosis (liver) and circulatory system (blood), with negligible deposition in other major organs (kidney, heart, lungs). Although we could not show complete clearance of our MNPs within the time frame tested, future studies should focus on combining MHT with immunotherapy, and target tumors at a much-reduced iron dose, consequently improving in vivo clearance rate, and hence overcoming the limitations of MHT in clinical therapy.