Combination therapy of multiple drugs through a single system is exhibiting high therapeutic effects. We investigate nanocarrier mediated inhibitory effects of topotecan (TPT) and quercetin (QT) on triple negative breast cancer (TNBC) (MDA-MB-231) and multi drug resistant (MDR) type breast cancer cells (MCF-7) with respect to cellular uptake efficiency and therapeutic mechanisms as in vitro and in vivo. The synthesized mesoporous silica nanoparticle (MSN) pores used for loading TPT; the outer of the nanoparticles was decorated with poly (acrylic acid) (PAA)-Chitosan (CS) as anionic inner-cationic outer layer respectively and conjugated with QT. Subsequently, grafting of arginine-glycine-aspartic acid (cRGD) peptide on the surface of nanocarrier (CPMSN) thwarted the uptake by normal cells, but facilitated their uptake in cancer cells through integrin receptor mediated endocytosis and the dissociation of nanocarriers due to the ability to degrade of CS and PAA in acidic pH, which enhance the intracellular release of drugs. Subsequently, the released drugs induce remarkable molecular activation as well as structural changes in tumor cell endoplasmic reticulum, nucleus and mitochondria that can trigger cell death. The valuable CPMSNs may open up new avenues in developing targeted therapeutic strategies to treat cancer through serving as an effective drug delivery podium.

The increasing use of nano based-products induces the potential hazards from their manufacture, transportation, waste disposal and management processes. In this report, we emphasized the acute toxicity of silver nanoparticles (AgNPs) using freshwater fish Labeo rohita as an aquatic animal model. The AgNPs were synthesized using chemical reduction method and the formation of AgNPs was monitored by UV-Visible spectroscopy analysis. The functional groups, crystaline nature and morphological characterizations were carried out by fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and high resolution transmission electron microscopy (HRTEM) analysis. UV-Vis range was observed at 420 nm and XRD pattern showed that the particles are crystalline nature. HRTEM analysis revealed that the morphology of particles was spherical and size ranges between 50 and 100 nm. This investigation was extended to determine the potential acute toxicity, L. rohita was treated orally with the lethal concentration (LC 50 ) of AgNPs. The antioxidative responses were studied in the three major tissues such as gill, liver and muscle of L. rohita. The results of this investigation showed that increasing the concentration of AgNPs led to bioaccumulation of AgNPs in the major tissues. The haematological parameters showed significant alterations in the treated fish. The histological changes caused by chemically synthesized AgNPs demonstrated the damages in the tissues, primary lamella and blood vessels of L. rohita. The histological study also displayed the formation of vacuolation in liver and muscle when compared with untreated tissues (control) of L. rohita.

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