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.

No abstract

Cancer therapy with theranostic nanoparticles having the dual properties of concurrent delivery of therapeutics and its tracking offers a huge prospect to overcome the limitations of conventional therapy. Delivery of the nontoxic prodrug, which converts into the toxic drug due to cellular stimuli, offers a great deal of scope in cancer therapy. The paracetamol dimer (PD) generally considered as nontoxic is encapsulated with fluorescent silver nanocluster (Ag NC) embedded composite nanoparticles where it acts as a prodrug. This is possibly converted to a toxic metabolite due to elevated reactive oxygen species (ROS), leading to apoptosis mediated cell death. Conjugation of folic acid with these composite NPs offers the credibility of distinguishing between two different cancer cell lines such as HeLa, which overexpresses folic acid receptors, and A549, which down-regulates its expression, probed by the fluorescence intensity of Ag NCs. Importantly, Ag NCs along with PD synergistically induce prodrug mediated targeted cell death at a much reduced concentration of silver. Thus, theranostic nanocarriers have been developed offering the dual property of therapy and imaging based on the differential uptake.

Gene expression controls and commands cellular functions of organisms and is considered to be the prime marker of human health. Conventional laboratory techniques use organic dyes as probes for diagnosis, which are mostly toxic, considered as environmental hazards and also known to be carcinogenic. On the other hand, there is a unique opportunity for the development of facile techniques for performing sensitive detection of polymerase chain reaction (PCR) products by biocompatible nanomaterials, especially useful for on-site analyses in a resource-limited location. We report a rapid (2 min) one-step green synthesis of highly luminescent gold nanoclusters on dsDNA, using a single heating and cooling cycle like in PCR. The luminescence intensity of nanoclusters was found to increase with the amount of dsDNA, offering a convenient way for quantification of the dsDNA (PCR products). The ability of the gold nanoclusters to act as powerful probe for DNA quantification was demonstrated in two different cancer cell lines, namely, HeLa and A549.

The NFkB overexpression triggers drug resistance in many types of cancer by up-regulating anti-apoptotic genes. IkBa, an endogenous protein and natural inhibitor of NFkB, blocks translocation of NFkB from cytoplasm to nucleus and thereby, sensitizes cancer cells to external stimuli. Herein, we have cloned a PCR amplified cDNA of IkBa, and expressed the recombinant GST tagged IkBa in Escherichia coli BL21 (DE3) cells. The recombinant GST-IkBa was purified by glutathione-agarose affinity chromatography and characterized by Western blot, MALDI-TOF, UV-Vis spectroscopy and circular dichroism spectroscopy. The GST-IkBa recombinant protein was encapsulated within polyvinyl alcohol (PVA)/polyvinyl pyrrolidone (PVP) hydrogel nanocarrier (NC) and then characterized by transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS) and zeta potential measurements. The pH-dependent protein release was performed in vitro to study the pH tunability of the hydrogel NCs. Furthermore, the therapeutic efficacy of GST-IkBa loaded hydrogel NCs was evaluated on HeLa (cervical carcinoma) cells by cytotoxicity assay and cell cycle analysis. TUNEL assay by flow cytometry confirmed apoptosis of HeLa cells. Administration of GST-IkBa by hydrogel NCs showed significant cell growth inhibition of drug resistant U87MG cells in combination with 5-FU. Our results essentially attributed the hydrogel NC-mediated administration of recombinant GST-IkBa as a novel recombinant protein therapeutic approach for cancer, which may further be regimented in combination therapy.