Gold nanoconjugates reinforce the potency of conjugated cisplatin and doxorubicin.

Osteosarcoma or osteogenic sarcoma is the most common and prevalent cancerous tumor of bone and occurs especially in children and teens. Recent treatment strategy includes a combination of both chemotherapy and surgeries. Although, the use of single drug-based chemotherapy treatment remains unsatisfactory. Therefore, combinatorial therapy has emerged as a potential strategy for treatment with limited side- effects. Here, we evaluated the combinatorial anticancerous effect of cisplatin (CIS) and doxorubicin (DOX) bioconjugated bromelain encapsulated gold nanoparticles (B-AuNPs conjugated CIS and DOX) in the treatment of osteosarcoma. The synthesized B-AuNPs conjugated CIS and DOX were characterized by various characterization techniques like UV-vis spectroscopy, TEM, DLS and zeta potential to ensure the synthesis, size, shape, size distribution and stability. Drug loading efficiency bioconjugation of CIS and DOX was ensured by UV-vis spectroscopy. Bioconjugation of CIS and DOX was further confirmed using UV-vis spectroscopy, TEM, DLS, Zeta potential and FT-IR analysis. The combinatorial effect of CIS and DOX in B-AuNPs conjugated CIS and DOX showed highly improved potency against MG-63 and Saos-2 cells at a very low concentration where primary osteoblasts didn't show any cytotoxic effect. The apoptotic effect of B-AuNPs conjugated CIS and DOX on osteosarcoma and primary osteoblasts cells were analyzed by increased permeability of the cell membrane, condensed chromatin and deep blue fluorescent condensed nucleus. The results clearly showed that B-AuNPs conjugated CIS and DOX significantly improved the potency of both the chemotherapeutic drugs by delivering them specifically into the nucleus of cancer cells through caveolae-dependent endocytosis. Thus, the greater inhibitory effect of combinatorial drugs (B-AuNPs conjugated CIS and DOX) over single drug based chemotherapy would be of great advantage during osteosarcoma treatment.

Biogenic terbium oxide nanoparticles as the vanguard against osteosarcoma.

The synthesis of inner transition metal nanoparticles via an ecofriendly route is quite difficult. This study, for the first time, reports synthesis of terbium oxide nanoparticles using fungus, Fusarium oxysporum. The biocompatible terbium oxide nanoparticles (Tb2O3 NPs) were synthesized by incubating Tb4O7 with the biomass of fungus F. oxysporum. Multiple physical characterization techniques, such as UV-visible and photoluminescence spectroscopy, TEM, SAED, and zeta-potential were used to confirm the synthesis, purity, optical and surface characteristics, crystallinity, size, shape, distribution, and stability of the nanoemulsion of Tb2O3 NPs. The Tb2O3 NPs were found to inhibit the propagation of MG-63 and Saos-2 cell-lines (IC50 value of 0.102µg/mL) and remained non-toxic up to a concentration of 0.373µg/mL toward primary osteoblasts. Cell viability decreased in a concentration-dependent manner upon exposure to 10nm Tb2O3 NPs in the concentration range 0.023-0.373µg/mL. Cell toxicity was evaluated by observing changes in cell morphology, cell viability, oxidative stress parameters, and FACS analysis. Morphological examinations of cells revealed cell shrinkage, nuclear condensation, and formation of apoptotic bodies. The level of ROS within the cells-an indicator of oxidative stress was significantly increased. The induction of apoptosis at concentrations ≤IC50 was corroborated by 4',6-diamidino-2-phenylindole dihydrochloride (DAPI) staining (DNA damage and nuclear fragmentation). Flow-cytometric studies indicated that the response was dose dependent with a threshold effect.