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Treatment of persistent biofilm infections has turned out to be a formidable challenge even with broad-spectrum antibiotic therapies. In this direction, intelligent micromachines may serve as active mechanical means to dislodge such deleterious bacterial communities. Herein, we have designed biocompatible micromotors from tea buds, namely, T-Budbots, which shows the capacity to be magnetically driven on a biofilm matrix and remove or fragment biofilms with precision, as a part of the proposed non-invasive "Kill-n-Clean" strategy. In a way, we present a bactericidal robotic platform decorated with magnetite nanoparticles aimed at clearing in vitro biofilms present on the surfaces. We have also shown that the smart porous T-Budbots can integrate antibiotic ciprofloxacin due to electrostatic interaction on their surface to increase their antibacterial efficacy against dreadful pathogenic bacterial communities of Pseudomonas aeruginosa and Staphylococcus aureus . It is noteworthy that the release of this drug can be controlled by tuning the surrounding pH of the T-Budbots. For example, while the acidic environment of the biofilm facilitates the release of antibiotics from the porous T-Budbots, the drug release was rather minimal at higher pH. The work represents a first step in the involvement of a plant-based microbot exhibiting magneto-robotic therapeutic properties, providing a non-invasive and safe approach to dismantle harmful biofilm infections.

The increase in bacterial infection and antibiotic resistance has posed a severe threat to the human health. This threat has warranted an imperative demand for the development of a new and effective bactericidal material to eradicate the antibiotic-resistant pathogenic bacteria. In this work, we report the wash-free imaging of Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative) bacteria using cationic conjugated polyelectrolyte[9,9-bis(6'-methylimidazoliumbromide)hexyl-fluorene- co-4,7-(2,1,3-benzothiadiazole)] (PFBT-MI) based on aggregation-induced fluorescence resonance energy transfer (FRET). Cationic imidazolium group strapped on the polymer side chain not only increases its solubility in water but also helps in binding with the negatively charged bacterial membrane via electrostatic interactions to turn on its bright yellow emission. The change in the fluorescence color of conjugated polyelectrolyte in the presence of bacteria could be visualized very easily via naked eyes under a UV lamp (365 nm). Furthermore, the antibacterial activity of PFBT-MI against both S. aureus and E. coli was observed because of the amphiphilic nature of the conjugated polyelectrolyte which in turn is due to the presence of ionic functionality and conjugated polymer backbone that can intercalate very proficiently into the bacterial membrane, which disrupts the membrane integrity and thus results in toxicity. Morphologically, the membrane damage was perceived via field emission scanning electron microscopy (FESEM) images, which clearly indicated the disruption of cell membrane upon exposure to PFBT-MI. The PFBT-MI acts as an effective antibacterial agent, with a minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) value of (30 μM or 23.7 μg/mL) and (60 μM or 47.7 μg/mL) for S. aureus and for E. coli (60 μM or 47.7 μg/mL) and (100 μM or 79 μg/mL), respectively. Moreover, PFBT-MI shows less cytotoxicity against mammalian cells at concentration greater than MIC.

A phenylboronic acid templated gold nanocluster probe was developed to detect biomarker mucin by a noninvasive fluorescence-based method using a point-of-care smartphone-based fluorescence detection device. The gold nanocluster probe is able to detect mucin specifically. The same probe was applied for in vitro targeted bioimaging of HeLa and Hep G2 cancer cells, and it demonstrated specific therapeutic effects toward cancer cells as well as multicellular tumor spheroids imparting theranostic properties. The module is found to be more effective toward HeLa cells, and a pathway of cell death was established using flow-cytometry-based assays.

Transferrin (Tf)-templated luminescent blue copper nanoclusters (Tf-Cu NCs) are synthesized. They are further formulated into spherical Tf-Cu NC-doxorubicin nanoparticles (Tf-Cu NC-Dox NPs) based on electrostatic interaction with doxorubicin (Dox). The as-synthesized Tf-Cu NC-Dox NPs are explored for bioimaging and targeted drug delivery to delineate high therapeutic efficacy. Förster resonance energy transfer (FRET) within the Tf-Cu NC-Dox NPs exhibited striking red luminescence, wherein the blue luminescence of Tf-Cu NCs (donor) is quenched due to absorption by Dox (acceptor). Interestingly, blue luminescence of Tf-Cu NCs is restored in the cytoplasm of cancer cells upon internalization of the NPs through overexpressed transferrin receptor (TfR) present on the cell surface. Finally, gradual release of Dox from the NPs leads to the generation of its red luminescence inside the nucleus. The biocompatible Tf-Cu NC-Dox NPs displayed superior targeting efficiency on TfR overexpressed cells (HeLa and MCF-7) as compared to the cells expressing less TfR (HEK-293 and 3T3-L1). Combination index (CI) revealed synergistic activity of Tf-Cu NCs and Dox in Tf-Cu NC-Dox NPs. In vivo assessment of the NPs on TfR positive Daltons lymphoma ascites (DLA) bearing mice revealed significant inhibition of tumor growth rendering prolonged survival of the mice.

Phthalocyanines and their main group and metal complexes are important classes of organic semiconductor materials but are usually highly insoluble and so frequently need to be processed by vacuum deposition in devices. We report two highly soluble silicon phthalocyanine (SiPc) diester compounds and demonstrate their potential as organic semiconductor materials. Near-infrared (λ(EL) = 698-709 nm) solution-processed organic light-emitting diodes (OLEDs) were fabricated and exhibited external quantum efficiencies (EQEs) of up to 1.4%. Binary bulk heterojunction solar cells employing P3HT or PTB7 as the donor and the SiPc as the acceptor provided power conversion efficiencies (PCE) of up to 2.7% under simulated solar illumination. Our results show that soluble SiPcs are promising materials for organic electronics.

Highly fluorescent red copper nanoclusters (Cu NCs) were synthesized in aqueous medium in the presence of dihydrolipoic acid and poly(vinylpyrrolidone) (PVP). The Cu NCs, in solid form, were stable, retained their optical properties for a month, and could be redispersed for use when required. The NCs in aqueous medium exhibited pH-tunable reversible optical properties. The PVP stabilized NCs, when converted into hydrogel by cross-linking with poly(vinyl alcohol), delivered anticancer drug to cervical cancer (HeLa) cells, thereby inducing apoptotic cell death. The red emission properties of the Cu NCs in the hydrogel were used for optical imaging as well as for flow cytometric probe of cellular uptake. Cell viability assay, Caspase3 assay, and cell cycle analyses demonstrated that the Cu NCs present in the hydrogel composite exhibited synergy of action, along with the drug, cisplatin, against HeLa cells.

Highly fluorescent copper nanoclusters (Cu NCs) have been synthesized using single-step reduction of copper sulfate by hydrazine in the presence of lysozyme. The fluorescence quantum yield was measured to be as high as 18%. The emission was also found to be dependent on the excitation wavelength. Mass spectrometric analyses indicated the presence of species corresponding to Cu2 to Cu9. Transmission electron microscopic analyses indicated the formation of agglomerated particles of average diameter of 2.3 nm, which were constituted of smaller particles of average diameter of 0.96 nm. They were found to be stable between pH 4 and 10 and in addition having excellent chemical and photostability. The noncytotoxic NCs were used to successfully label cervical cancer HeLa cells.

Advanced theranostic materials hold promise for targeted delivery of drugs, with the ability to follow the transport as well as its consequences. This should, ideally, be possible with minimum invasive surgery and having no or minimum cytotoxicity of the materials. It requires development of newer materials whose physical properties would allow for easy probe, which could carry the therapeutic molecules, which will be stable under physiological conditions, and at the same time would be able to permeate barriers to the target. We report the development of a composite consisting of highly fluorescent Au nanoclusters and the biopolymer chitosan, which could easily be converted into nanoparticles and would form a stable polyplex with suicide gene for induction of apoptosis in cervical cancer cells. The simultaneous red, green, and blue fluorescence from the nanoclusters provided convenient optical imaging and flow cytometry probes, without having to use additional dyes. Moreover, the colloidal nanocluster-polymer composite could be converted into solid film and be stored with the retention of optical properties. The pH tunable optical properties in the medium were also intact in the films that quickly dissolved in water with retention of properties.

We report herein the synthesis of a new composite consisting of Cu nanoparticles (NPs) and chitosan (CS), which has been found to be stable in the presence of molecular iodine and has also high antimicrobial activities. The composite could be obtained when aqueous CuSO(4) was treated with hydrazine in the presence of CS. The spherical Cu NPs present in the composite were of average diameters 8±4 nm. The NPs were unstable in atmospheric conditions leading to the formation of oxides of Cu. On the other hand, when molecular iodine was added to the medium following synthesis the NPs were rather stable. Studies of antibacterial property were carried out on Gram-negative green fluorescent expressing Escherichia coli bacteria & Gram-positive Bacillus cereus bacteria. The minimum inhibitory concentration (MIC) of the iodinated composite on Escherichia coli was found to be 130.8 μg/mL, which contained 21.5 μg/mL Cu NPs. This determined value of MIC for Cu NPs was much lower than those reported in the literature. Zeta potential (ζ) measurements supported an attractive interaction between iodinated CS-Cu NP composite and bacteria which was further supported by electron microscopic images. Electron microscopic and flow cytometric studies revealed that the iodinated CS-Cu NP composite was attached to the bacterial cell wall, which caused irreversible damage to the membrane, eventually leading to cell death. Mechanism of bactericidal action of the iodinated composite is discussed in light of our findings., (© 2012 American Chemical Society)

We report the development of a chitosan nanocarrier (NC)-based delivery of silver nanoparticles (Ag NPs) to mammalian cells for induction of apoptosis at very low concentrations of the NPs. The cytotoxic efficacy of the Ag NP-nanocarrier (Ag-CS NC) system in human colon cancer cells (HT 29) was examined by morphological analyses and biochemical assays. Cell viability assay demonstrated that the concentration of Ag NPs required to reduce the viability of HT 29 cells by 50% was 0.33 μg mL(-1), much less than in previously reported data. The efficient induction of apoptosis by Ag-CS NCs was confirmed by flow cytometry. Additionally, the characteristic nuclear and morphological changes during apoptotic cell death were investigated by fluorescence and scanning electron microscopy (SEM), respectively. The involvement of mitochondrial pathway of cell death in the Ag-CS NCs induced apoptosis was evident from the depolarization of mitochondrial membrane potential (ΔΨ(m)). Real time quantitative RT-PCR analysis demonstrated the up-regulation of caspase 3 expression which was further reflected in the formation of oligo-nucleosomal DNA "ladders" in Ag-CS NCs treated cells, indicating the important role of caspases in the present apoptotic process. The increased production of intracellular ROS due to Ag-CS NCs treatment indicated that the oxidative stress could augment the induction of apoptosis in HT 29 cells in addition to classical caspase signaling pathway. The use of significantly low concentration of Ag NPs impregnated in chitosan nanocarrier is a much superior approach in comparison to the use of free Ag NPs in cancer therapy.