Shazid Md. Sharker

Target delivery of β-cyclodextrin/paclitaxel complexed fluorescent carbon nanoparticles: externally NIR light and internally pH sensitive-mediated release of paclitaxel with bio-imaging

The development of cooperative drug delivery systems that can detect and target the disease site, with rapid trigger controlled drug release (internally and externally), is widely expected to change the landscape of future drug carriers. In this study a drug delivery system was developed for the cancer-targeted release of chemotherapeutic agents inside living cells. This system is an environment sensitive (pH), and external photothermally remote controlled, cooperative image-guided drug delivery matrix. Partially carbonized fluorescence hyaluronic acid (HA-FCN) was conjugated with boronic acid (BA) to promote the formation of boronate ester with diol groups of β-cyclodextrin (CD) [HA-FCN-CD]. The pH influence mediated release of paclitaxel (PTX) from the CD cavity of HA-FCN-CD was utilized for targeted cancer bioimaging. This active-target delivery system (HA-FCN-CD-PTX) was found to show optical absorption properties similar to those of the near infrared (NIR) light sensitive carbonized material. This system exploits acidity for triggered drug release and rapid generation of mild photothermal heat to trigger burst release of PTX. Cooperative guided bioimaging that employs both internal pH responsive and external NIR controlled drug carriers is a promising method for chemotherapeutic release that can be adjusted according to physiological needs.

In Vitro and In Vivo Tumor Targeted Photothermal Cancer Therapy Using Functionalized Graphene Nanoparticles

Despite the tremendous progress that photothermal therapy (PTT) has recently achieved, it still has a long way to go to gain the effective targeted photothermal ablation of tumor cells. Driven by this need, we describe a new class of targeted photothermal therapeutic agents for cancer cells with pH responsive bioimaging using near-infrared dye (NIR) IR825, conjugated poly(ethylene glycol)-g-poly(dimethylaminoethyl methacrylate) (PEG-g-PDMA, PgP), and hyaluronic acid (HA) anchored reduced graphene oxide (rGO) hybrid nanoparticles. The obtained rGO nanoparticles (PgP/HA-rGO) showed pH-dependent fluorescence emission and excellent near-infrared (NIR) irradiation of cancer cells targeted in vitro to provide cytotoxicity. Using intravenously administered PTT agents, the time-dependent in vivo tumor target accumulation was exactly defined, presenting eminent photothermal conversion at 4 and 8 h post-injection, which was demonstrated from the ex vivo biodistribution of tumors. These tumor environment responsive hybrid nanoparticles generated photothermal heat, which caused dominant suppression of tumor growth. The histopathological studies obtained by H&E staining demonstrated complete healing from malignant tumor. In an area of limited successes in cancer therapy, our translation will pave the road to design stimulus environment responsive targeted PTT agents for the safe eradication of devastating cancer.

Functionalized biocompatible WO3 nanoparticles for triggered and targeted in vitro and in vivo photothermal therapy.

We report on dopamine-conjugated hyaluronic acid (HA-D), a mussel-inspired facile capping material that can modify tungsten oxide (WO3) nanoparticles to be both biocompatible and targetable, allowing precise delivery (WO3-HA) to a tumor site. Near-infrared (NIR) irradiated WO3-HA showed a rapid and substantial rise in photothermal heat to complete in vitro thermolysis of malignant MDAMB and A549 cancer cellsbut was found to be relatively less sensitive to normal MDCK cells. A long-term in vivo investigation of ~10 nm HA thickness on WO3 (WO3-HA) nanoparticles demonstrated efficient photo-thermal conversion with time-dependent tumor target accumulation. This long-termin vivo survival study ofWO3-HA showed promising biocompatibility, with a complete recovery from malignant tumor. Due to the importance of keeping simplicity in the design of therapeutic nanoparticles, we therefore expect that this facile scheme (HA-D) would contribute to the biocompatible development of versatile metallic nanoparticles for photothermal applications.

Iron Oxide@PEDOT-Based Recyclable Photothermal Nanoparticles with Poly(vinylpyrrolidone) Sulfobetaines for Rapid and Effective Antibacterial Activity.

Growing microbial resistance that renders antibiotic treatment vulnerable has emerged, attracting a great deal of interest in the need to develop alternative antimicrobial treatments. To contribute to this effort, we report magnetic iron oxide (Fe3O4) nanoparticles (NPs) coated with catechol-conjugated poly(vinylpyrrolidone) sulfobetaines (C-PVPS). This negatively charged Fe3O4@C-PVPS is subsequently encapsulated by poly(3,4-ethylenedioxythiophene) (PEDOT) following a layer-by-layer (LBL) self-assembly method. The obtained Fe3O4@C-PVPS:PEDOT nanoparticles appear to be novel NIR-irradiated photothermal agents that can achieve effective bacterial killing and are reusable after isolation of the used particles using external magnetic fields. The recyclable Fe3O4@C-PVPS:PEDOT NPs exhibit a high efficiency in converting photothermal heat for rapid antibacterial effects against Staphylococcus aureus and Escherichia coli. In this study, antibacterial tests for repeated uses maintained almost 100% antibacterial efficiency during three cycles and provided rapid and effective killing of 99% Gram-positive and -negative bacteria within 5 min of near-infrared (NIR) light exposure. The core-shell nanoparticles (Fe3O4@C-PVPS:PEDOT) exhibit the required stability, and their paramagnetic nature means that they rapidly convert photothermal heat sufficient for use as NIR-irradiated antibacterial photothermal sterilizing agents.

Light Controllable Surface Coating for Effective Photothermal Killing of Bacteria

Although the electronic properties of conducting films have been widely explored in optoelectronic fields, the optical absorption abilities of surface-coated films for photothermal conversion have been relatively less explored in the production of antibacterial coatings. Here, we present catechol-conjugated poly(vinylpyrrolidone) sulfobetaine (PVPS) and polyaniline (PANI) tightly linked by ionic interaction (PVPS:PANI) as a novel photothermal antibacterial agent for surface coating, which can absorb broadband near-infrared (NIR) light. Taking advantage of the NIR light absorption, this coating film can release eminent photothermal heat for the rapid killing of surface bacteria. The NIR light triggers a sharp rise in photothermal heat, providing the rapid and effective killing of 99.9% of the Gram-positive and -negative bacteria tested within 3 min of NIR light exposure when used at the concentration of 1 mg/mL. Although considerable progress has been made in the design of antibacterial coatings, the user control of NIR-irradiated rapid photothermal destruction of surface bacteria holds increasing attention beyond the traditional boundaries of typical antibacterial surfaces.

Photo- and pH-Tunable Multicolor Fluorescent Nanoparticle-Based Spiropyran- and BODIPY-Conjugated Polymer with Graphene Oxide

We report a stimuli-responsive fluorescent nanomaterial, based on graphene oxide coupled with a polymer conjugated with photochromic spiropyran (SP) dye and hydrophobic boron dipyrromethane (BODIPY) dye, for application in triggered target multicolor bioimaging. Graphene oxide (GO) was reduced by catechol-conjugated polymers under mildly alkaline conditions, which enabled to formation of functionalized multicolor graphene nanoparticles that can be induced by irradiation with UV light and by changing the pH from acidic to neutral. Investigation of these nanoparticles by using AFM, fluorescence emission, and in vitro cell and in vivo imaging revealed that they show different tunable colors in bioimaging applications and, more specifically, in cancer-cell detection. The stability, biocompatibility, and quenching efficacy of this nanocomposite open a different perspective for cell imaging in different independent colors, sequentially and simultaneously.

Photothermal conversion upon near-infrared irradiation of fluorescent carbon nanoparticles formed from carbonized polydopamine

Fluorescence and photothermal conversion mediated by near-infrared radiation (NIR) is reported for carbonized polydopamine nanoparticles. Carbonized polydopamine demonstrated excitation-dependent fluorescence emission, together with NIR-responsive photothermal conversion properties. The concentration-dependent photothermal heating from carbonized fluorescent carbon nanoparticles-polydopamine (FNP-pDA) induces hyperthermal killing of both cancer cell lines and bacteria in vitro. Although most of the dopamine moieties of polydopamine become dehydrated upon carbonization, the remaining dopamine-hydroxyl groups can confer adhesive properties. These fluorescent coatings are compatible with many substrates, and the surface passivation of FNP-pDA with polyethylene glycol improves quantum yield and extends fluorescence lifetimes. The novel infrared-responsive photothermal and fluorescent carbon nanoparticles reported here show promise for a range of potential biomedical and research applications.

Chemical and biological studies of Kalanchoe pinnata (Lam.) growing in Bangladesh

Abstract Objective To isolate compounds from K. pinnata and elucidate their structures and to explore preliminary antioxidant, antimicrobial, cytotoxic and thombolytic activities of extractives of the plant. Methods The methanol extract of whole plant of K. pinnata has been subjected to different chromatographic separation and purification processes to isolate the secondary metabolites. The structures of the isolated compounds have been elucidated by extensive NMR studies. The free radical scavenging activity of the crude extract and its different Kupchan fractions were determined on stable radical DPPH. In vitro antimicrobial activity was determined by the disk diffusion method. Cytotoxicity screening has been performed against Artemia salina . Total phenolics content, membrane stabilizing activity and thombolytic activities were assessed by following established protocol. Results The isolated compounds were identified as glut-5(6)-en-3-one, taraxerone, 3β-friedelanol, β-amyrin-3-acetate, 3,5,7,3′,5′-pentahydroxyflavone and β-sitosterol. The chloroform soluble fraction showed potent antioxidant activity of (IC 50 = 80.0 μg/mL) and significant cytotoxicity, while the crude extract demonstrated noticeable total polyphenol content (149.24 mg of GAE/gm of extractive), moderate membrane stabilizing activity and inhibition of clot lysis of blood. Conclusions The obtained results rationalize the folkloric use of the plant and can be further investigated to isolate the active compounds responsible for the biological activities.

Antinociceptive and bioactivity of leaves of Murraya paniculata (L.) Jack, Rutaceae

The results of antinociceptive and toxicological studies on the ethanol extract of the leaves of Murraya paniculata (L.) Jack, Rutaceae, are reported. The extract (250 and 500 mg/kg dosages) was found to produce a profound antinociceptive activity in a dose dependent manner. The extract showed considerable brine shrimp toxicity (LD50 = 32 μg/mL).

Determination of the binding sites of propranolol HCl on bovine serum albumin by direct and reverse procedures.

To characterize the binding site of propranolol hydrochloride, the free concentration of warfarin (site-I-specific probe) bound to BSA was measured upon the addition of propranolol hydrochloride. It was found that the free concentration of warfarin sodium was increased from 100% (as % of initial) to 552.35% when the ratio of propranolol to BSA was increased 1-6. In contrast, under the same experimental conditions, when diazepam was used as a site-II-specific probe, the increment of the free concentration of diazepam by propranolol was from 100% (as % of initial) to 415.42. From these data it is evident that the increment of free concentration of warfarin sodium is obviously greater than that of diazepam by propranolol. So it can be concluded that propranolol preferentially binds to site-I. Again as the displacement of diazepam is quite enough it can also be suggested that propranolol in addition to site-I also binds to site-II on the BSA molecule but to a lower extent. Again in the reverse experiment, the free concentration of propranolol was increased from 100% (as % of initial) to 476% when warfarin to BSA ratio was 1-6 as shown, on the other hand, the free concentration of propranolol was increased from 100% (as % initial) to 222.39% when the ratio of diazepam to BSA was also 1-6. From the data it is clear that the increment of propranolol due to displacement by warfarin (site-I probe) is higher than that of propranolol when displaced by diazepam (site-II probe). Thus this reverse experiment also agrees with the previous experiment.