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Bioinert gold nanoparticles of various shapes and functionalities are widely accepted as contrast agents (CAs) for several modalities of imaging, viz., electron microscopy, computerized tomography (CT), X-ray and photoacoustic (PA) imaging. However, testing of novel compact-imaging probes for ocular diagnostic imaging is always challenging. Here, ultra-fast microwave oven synthesized gold nanocages (AuNcgs) were successfully demonstrated for high-contrast PA ocular imaging for the first time. Methods are described for the synthesis, characterization and application of quickly synthesized AuNcgs in diagnostic ocular imaging. PA and ultrasound (US) images were acquired using a commercial US imaging scanner integrated with a tunable nanosecond pulsed laser. This integrated hybrid-modality system is a combined PA and US platform for imaging which enabled acquiring of complementary structural and optical absorption-based information simultaneously. Initial experiments were conducted using tubings filled with solutions of different concentrations of quickly synthesized AuNcgs. Biological PA and US imagings were demonstrated using enucleated porcine eye samples. Based on the acquired results, it is envisaged that AuNcgs can be employed as a high strength PA CA to potentially diagnose ocular disease like uveal melanoma in the near future. MOE (Min. of Education, S’pore) Accepted version

Gold nanocages (AuNcgs) are well-studied, hollow, metallic nanostructures that have fascinated researchers in the fields of nanotechnology, materials science, photoelectronics, biotechnology, and medical science for the last decade. However, the time-consuming synthesis of AuNcgs has limited their widespread use in materials science and nano-biotechnology. A novel, ultra-fast, simple, and highly convenient method for the production of AuNcgs using microwave heating is demonstrated herein. This quick method of AuNcg synthesis requires mild laboratory conditions for large-scale production of AuNcgs. The microwave heating technique offers the advantage of precise mechanical control over the temperature and heating power, even for the shortest reaction period (i.e., seconds). Microwave-synthesized AuNcgs were compared with conventionally synthesized AuNcgs. Structural maneuver studies employing the conventionally produced AuNcgs revealed the formation of screw dislocations and a shift in the lattice plane. Detailed characterization of the microwave-generated AuNcgs was performed using high resolution transmission electron microscopy (HRTEM), scanning electron microscopy (SEM), X-ray powder diffraction (XRD), and spectroscopic techniques.

Despite aggressive surgical resections and combinatorial chemoradiations, certain highly malignant populations of tumor cells resurrect and metastasize. Mixed-grade cancer cells fail to respond to standard-of-care therapies by developing intrinsic chemoresistance and subsequently result in tumor relapse. Macroautophagy is a membrane trafficking process that underlies drug resistance and tumorigenesis in most breast cancers. Manipulating cellular homeostasis by a combinatorial nanotherapeutic model, one can evaluate the crosstalk between type I and type II cell death and decipher the fate of cancer therapy. Here, we present a multi-strategic approach in cancer targeting to mitigate the autophagic flux with subcellular toxicity via lysosome permeation, accompanied by mitochondrial perturbation and apoptosis. In this way, a nanoformulation is developed with a unique blend of a lysosomotropic agent, an immunomodulating sulfated-polysaccharide, an adjuvant chemotherapeutic agent, and a monoclonal antibody as a broad-spectrum complex for combinatorial nanotherapy of all breast cancers. To the best of our knowledge, this manuscript illustrates for the first time the applications of advanced microscopic techniques such as electron tomography, three-dimensional rendering and segmentation of subcellular interactions, and fate of the multifunctional therapeutic gold nanocages specifically targeted toward breast cancer cells.

Morusin, a water-insoluble prenylated flavonoid is known for its numerous medicinal properties. It manifests its anticancer potential by suppression of genes involved in tumor progression. However, poor solubility of the drug results in low bioavailability and rapid degradation thus hindering its clinical utilization. In order to overcome this, we have synthesized a niosome system composed of non-ionic surfactant span 60 and cholesterol using a thin-layer evaporation technique to improve the aqueous-phase solubility of the drug. Highly cytocompatible niosomes of 479 nm average size with smooth and uniform spherical morphology were synthesized in a facile manner. Unlike free morusin, nanomorusin was found to be freely dispersible in aqueous media. Having an extremely high drug entrapment efficiency (97%), controlled and sustained release of morusin resulting in enhanced therapeutic efficacy was observed in cancer cell lines of 4 different lineages. The results demonstrate that the morusin-niosome system is a promising strategy for enhanced anti-cancer activity against multiple cancer types and could be an indispensable tool for future targeted chemotherapeutic strategies.

A multifunctional nanoparticle based on carboxymethyl cellulose was developed. Folate group was attached to nanoparticle for specific recognition of cancerous cells and 5FU was encapsulated for delivering cytotoxicity. The whole system was able to track by the semiconductor quantum dots that were attached to the nanoparticle. The multifunctional nanoparticle was characterized by UV-VIS spectra, PL spectra, FTIR, TEM, SEM etc and was targeted to human breast cancer cell, MCF7. The biocompatibility of nanoparticle without drug and cytotoxicity rendered by nanoparticle with drug was studied with MCF7 and L929 cell lines. The epifluorescent images suggest that the folate-conjugated nanoparticles were more internalized by folate receptor positive cell line, MCF7 than the noncancerous L929 cells.

Extensive cancer research in the past few decades has identified the existence of a rare subpopulation of stem cells in the grove of cancer cells. These cells are known as the cancer stem cells marked by the presence of surface biomarkers, multi-drug resistance pumps and deregulated self-renewal pathways (SRPs). They have a crucial role in provoking cancer cells leading to tumorigenesis and its progressive metastasis. Cancer stem cells (CSCs) are much alike to normal stem cells in their self-renewal mechanisms. However, deregulations in the SRPs are seen in CSCs, making them resistant to conventional chemotherapeutic agents resulting in the tumor recurrence. Current treatment strategies in cancer fail to detect and differentiate the CSCs from their non-tumorigenic progenies owing to absence of specific biomarkers. Now, it has become imperative to understand complex functional biology of CSCs, especially the signaling pathways to design improved treatment strategies to target them. It is hopeful that the SRPs in CSCs offer a promising target to alter their survival strategies and impede their tumorigenic potential. However, there are many perils associated with the direct targeting method by conventional therapeutic agents such as off targets, poor bioavailability and poor cellular distribution. Recent evidences have shown an increased use of small molecule antagonists directly to target these SRPs may lead to severe side-effects. An alternative to solve these issues could be an appropriate nanoformulation. Nanoformulations of these molecules could provide an added advantage for the selective targeting of the pathways especially Hedgehog, Wnt, Notch and B-cell-specific moloney murine leukemia virus integration site 1 in the CSCs while sparing the normal stem cells. Hence, to achieve this goal a complete understanding of the molecular pathways corroborate with the use of holistic nanosystem (nanomaterial inhibition molecule) could possibly be an encouraging direction for future cancer therapy.