Insight into the Effect of Stabilizers on Anticancer and Antibacterial Activity of AgBiS2 Nanomaterial.

The near-infrared (NIR) light-absorbing AgBiS2 nanoparticles can be excited by single-wavelength light, which is the primary characteristic of a photo responsive platform. Chemical synthesis of nanomaterials inevitably requires long-chain organic surfactants or polymers to stabilize them in the nano regime. These stabilizing molecules barricade the interaction of nanomaterials with biological cells. We have produced stabilizer-free (sf-AgBiS2 ) and polymer-coated (PEG-AgBiS2 ) nanoparticles; and assessed their NIR mediated anticancer and antibacterial activity to evaluate the effect of stabilizers. sf-AgBiS2 showed better antibacterial activity against Gram-positive Staphylococcus aureus (S. aureus) and displayed excellent cytotoxicity against HeLa cells and live 3-D tumour spheroids compared to PEG-AgBiS2 both in presence and absence of NIR radiation. The photothermal therapy (PTT) results illustrated the tumour ablation ability of sf-AgBiS2 , which converted light into heat effectively up to 53.3 °C under NIR irradiation. This work demonstrates the importance of synthesizing stabilizer-free nanoparticles to produce safe and highly active PTT agents.

Magnesium-Catalyzed Dye-Embedded Polylactide Nanoparticles for the Effective Killing of Highly Metastatic B16F10 Melanoma Cells.

In the current research, dye-embedded polylactic acid (PLA) conjugate materials were synthesized using one-pot ring-opening polymerization (ROP), i.e., (dtHPLA) (2-[(2,4,6-trimethylphenyl) imino]-1(2H)-acenaphthylenone-reduced-PLA) and (dmHPLA) (monoiminoacenaphtheneone-reduced-PLA), and then, nanoparticles (NPs) were engineered in the size range of 150 ± 30 nm. P(dtHPLA) NPs were employed in the treatment of melanoma, an aggressive type of skin cancer, which mandates the development of novel techniques to enhance healing outcomes and eliminate adverse effects related to existing treatments. In addition to exhibiting strong intracellular absorption in the spheroid model, the P(dtHPLA) NPs exhibited a strong cytotoxic effect on B16F10 cells, which resulted in oxidative stress from the generation of reactive oxygen species (ROS) and cell death. Additionally, a live/dead experiment using P(dtHPLA) NPs revealed a notable reduction in cell viability.

Radiotherapy, photodynamic therapy, and cryoablation-induced abscopal effect: Challenges and future prospects.

Local therapy modalities such as radiation therapy, photodynamic therapy, photothermal therapy, and cryoablation have been used to treat localized tumors for decades. The discovery of the abscopal effect causes a paradigm shift where local therapy also causes systemic effects and leads to the remission of nonirradiated tumors. The abscopal effect of radiation therapy, alone or in combination with other treatments, has been extensively studied over the last six decades. However, the results are unsatisfactory in producing robust, reproducible, and long-lasting systemic effects. Although immunotherapy and radiation therapy are promising in producing the abscopal effect, the abscopal effect's mechanism is still unclear, owing to various factors such as irradiation type and dose and cancer type. This article reviews the research progress, clinical and preclinical evidence of the abscopal effect by various local therapies alone and in combination with chemotherapy and immunotherapy, case reports, and the current challenges in producing the abscopal effect by various local therapies, focusing on radiotherapy, photodynamic therapy, cryoablation, and the prospects for obtaining a robust, reproducible, and long-lasting abscopal effect.

An Isothiazolanthrone-Based Self-Assembling Anticancer Color-Changing Dye for Concurrent Imaging and Monitoring of Cell Viability.

We report the photophysical properties, self-assembly and biological evaluation of an isothiazolanthrone-based dye, 7-amino-6H-anthra[9,1-cd]isothiazol-6-one (AAT), which reveals anticancer properties and can be potentially used as dye for monitoring cell viability. The solvent-dependent photophysical studies suggest that the emission of AAT is sensitive to environment polarity due to which interesting changes in the colored emission may be observed owing to the charge transfer (CT) processes. AAT also self-assembles to tree-like branched morphologies and produce, a greenish emission inside the cells when imaged after short interval (15 mins) of incubation while a red fluorescence could be noted after 24 h. Interestingly, AAT also produce differential emission inside mouse normal cells as compared to its cancer cell lines since it possess anticancer activity. The experimental observations were also validated theoretically via computational modeling.

Alkaloid-rich fraction of Ervatamia coronaria sensitizes colorectal cancer through modulating AMPK and mTOR signalling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Ervatamia coronaria, a popular garden plant in India and some other parts of the world is known traditionally for its anti-inflammatory and anti-cancer properties. The molecular bases of these functions remain poorly understood. AIM OF THE STUDY: Efficacies of the existing therapies for colorectal cancer (CRC) are limited by their life-threatening side effects and unaffordability. Therefore, identifying a safer, efficient, and affordable therapeutic is urgent. We studied the anti-CRC activity of an alkaloid-rich fraction of E. coronaria leaf extracts (AFE) and associated underlying mechanism. MATERIALS AND METHODS: Activity guided solvant fractionation was adopted to identify the activity in AFE. Different cell lines, and tumor grown in syngeneic mice were used to understand the anti-CRC effect. Methodologies such as LCMS, MTT, RT-qPCR, immunoblot, immunohistochemistry were employed to understand the molecular basis of its activity. RESULTS: We showed that AFE, which carries about six major compounds, is highly toxic to colorectal cancer (CRC) cells. AFE induced cell cycle arrest at G1 phase and p21 and p27 genes, while those of CDK2, CDK-4, cyclin-D, and cyclin-E genes were downregulated in HCT116 cells. It predominantly induced apoptosis in HCT116p53+/+ cells while the HCT116p53-/- cells under the same treatment condition died by autophagy. Notably, AFE induced upregulation of AMPK phosphorylation, and inhibition of both of the mTOR complexes as indicated by inhibition of phosphorylation of S6K1, 4EBP1, and AKT. Furthermore, AFE inhibited mTOR-driven conversion of cells from reversible cell cycle arrest to senescence (geroconversion) as well as ERK activity. AFE activity was independent of ROS produced, and did not primarily target the cellular DNA or cytoskeleton. AFE also efficiently regressed CT26-derived solid tumor in Balb/c mice acting alone or in synergy with 5FU through inducing autophagy as a major mechanism of action as indicated by upregulation of Beclin 1 and phospho-AMPK, and inhibition of phospho-S6K1 levels in the tumor tissue lysates. CONCLUSION: AFE induced CRC death through activation of both apoptotic and autophagy pathways without affecting the normal cells. This study provided a logical basis for consideration of AFE in future therapy regimen to overcome the limitations associated with existing anti-CRC chemotherapy.

Biocompatible functionalized AuPd bimetallic nanoparticles decorated on reduced graphene oxide sheets for photothermal therapy of targeted cancer cells.

Graphene, which is a unique 2D nanomaterials has received widespread attention for photothermal therapy (PTT) application. Here, we have designed the nanocomposite using polydopamine (PDA) functionalized reduced graphene oxide (rGO) nanosheets and bimetallic AuPd nanoparticles (NPs). The bimetallic AuPd nanoparticles decorated PDA functionalized rGO (AuPd-rGO/PDA) nanocomposite is synthesized by simple chemical reduction technique resulting in an average size of AuPd bimetallic nanostructure of 4.18 nm. The photothermal activity of the AuPd-rGO/PDA nanocomposite is explored under the irradiation of near infrared (NIR) laser sources of wavelength 915 nm. The temperature rises nearly 51 ± 3 °C within 3 min of irradiation NIR laser light resulting in the ablation of MDAMB-231 cancer cells up to concentration of 25 µg mL-1 of AuPd-rGO/PDA nanocomposite. This high performance of the ablation of cancer cells by photothermal therapy technique was facilitated using a low concentration of the nanocomposite by the synergistic effects of the bimetallic AuPd as well as rGO and PDA functionalization. The AuPd-rGO/PDA nanocomposite demonstrated the high biocompatibility towards normal healthy cell lines (L929) and exhibits survival efficiency of more than 85%. We also demonstrated the biocompatibility of the AuPd-rGO/PDA nanocomposite materials on the zebrafish embryos (Danio rerio). This work thus illustrates that the AuPd-rGO/PDA nanocomposite could behave as favourable nanoplatform for tumor therapeutics.

Ag and Au nanoparticles/reduced graphene oxide composite materials: Synthesis and application in diagnostics and therapeutics.

The exceptional electrical, thermal, optical and mechanical properties have made two dimensional sp2 hybridized graphene a material of choice in both academic as well as industrial research. In the last few years, researchers have devoted their efforts towards the development of graphene/polymer, graphene/metal nanoparticle and graphene/ceramic nanocomposites. These materials display excellent mechanical, electrical, thermal, catalytic, magnetic and optical properties which cannot be obtained separately from the individual components. Fascinating physical and chemical properties are displayed by noble metal nanomaterials and thus they represent model building blocks for modifying nanoscale structures for diverse applications extending from catalysis, optics to nanomedicine. Insertion of noble metal (Au, Ag) nanoparticles (NPs) into chemically derived graphene is thus of primary importance to open new avenues for both materials in various fields where the specific properties of each material act synergistically to provide hybrid materials with exceptional performances. This review attempts to summarize the different synthetic procedures for the preparation of Ag and Au NPs/reduced graphene oxide (rGO) composites. The synthesis processes of metal NPs/rGO composites are categorised into in-situ and ex-situ techniques. The in-situ approach consists of simultaneous reduction of metal salts and GO to obtain metal NPs/rGO nanocomposite materials, while in the ex-situ process, the metal NPs of desired size and shape are first synthesized and then transferred onto the GO or rGO matrix. The application of the Ag NPs and Au NPs/rGO composite materials in the area of biomedical (drug delivery and photothermal therapy) and biosensing are the focus of this review article.

Enhanced EPR directed and Imaging guided Photothermal Therapy using Vitamin E Modified Toco-Photoxil.

Herein we report synthesis, characterization and preclinical applications of a novel hybrid nanomaterial Toco-Photoxil developed using vitamin E modified gold coated poly (lactic-co-glycolic acid) nanoshells incorporating Pgp inhibitor d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a highly inert and disintegrable photothermal therapy (PTT) agent. Toco-Photoxil is highly biocompatible, physiologically stable PTT material with an average diameter of 130 nm that shows good passive accumulation (2.3% ID) in solid tumors when delivered systemically. In comparison to its surface modified counterparts such as IR780-Toco-Photoxil, FA-Toco-Photoxil or FA-IR780-Toco-Photoxil accumulation are merely ~0.3% ID, ~0.025% ID and ~0.005% ID in folate receptor (FR) negative and positive tumor model. Further, Toco-Photoxil variants are prepared by tuning the material absorbance either at 750 nm (narrow) or 915 nm (broad) to study optimal therapeutic efficacy in terms of peak broadness and nanomaterial's concentration. Our findings suggest that Toco-Photoxil tuned at 750 nm absorbance is more efficient (P = 0.0097) in preclinical setting. Toco-Photoxil shows complete passiveness in critical biocompatibility test and reasonable body clearance. High tumor specific accumulation from systemic circulation, strong photothermal conversion and a very safe material property in body physiology makes Toco-Photoxil a superior and powerful PTT agent, which may pave its way for fast track clinical trial in future.