Raju Vivek

Multifunctional HER2-Antibody Conjugated Polymeric Nanocarrier-Based Drug Delivery System for Multi-Drug-Resistant Breast Cancer Therapy

Nanotechnology-based medical approaches have made tremendous potential for enhancing the treatment efficacy with minimal doses of chemotherapeutic drugs against cancer. In this study, using tamoxifen (Tam), biodegradable antibody conjugated polymeric nanoparticles (NPs) was developed to achieve targeted delivery as well as sustained release of the drug against breast cancer cells. Poly(D,L-lactic-co-glycolic acid) (PLGA) NPs were stabilized by coating with poly(vinyl alcohol) (PVA), and copolymer polyvinyl-pyrrolidone (PVP) was used to conjugate herceptin (antibody) with PLGA NPs for promoting the site-specific intracellular delivery of Tam against HER2 receptor overexpressed breast cancer (MCF-7) cells. The Tam-loaded PVP-PLGA NPs and herceptin-conjugated Tam-loaded PVP-PLGA NPs were characterized in terms of morphology, size, surface charge, and structural chemistry by dynamic light scattering (DLS), Transmission electron microscopy (TEM), ζ potential analysis, 1H nuclear magnetic resonance (NMR), and Fourier transform infrared (FT-IR) spectroscopy. pH-based drug release property and the anticancer activity (in vitro and in vivo models) of the herceptin conjugated polymeric NPs were evaluated by flow cytometry and confocal image analysis. Besides, the extent of cellular uptake of drug via HER2 receptor-mediated endocytosis by herceptin-conjugated Tam-loaded PVP-PLGA NPs was examined. Furthermore, the possible signaling pathway of apoptotic induction in MCF-7 cells was explored by Western blotting, and it was demonstrated that drug-loaded PLGA NPs were capable of inducing apoptosis in a caspase-dependent manner. Hence, this nanocarrier drug delivery system (DDS) not only actively targets a multidrug-resistance (MDR) associated phenotype (HER2 receptor overexpression) but also improves therapeutic efficiency by enhancing the cancer cell targeted delivery and sustained release of therapeutic agents.

Corrigendum: Combinatorial nanocarrier based drug delivery approach for amalgamation of anti-tumor agents in breast cancer cells: an improved nanomedicine strategy

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.

Protein regulation and Apoptotic induction in human breast carcinoma cells (MCF-7) through lectin from G. beauts.

Lectins are proteins that show a variety of biological activities. Nevertheless, information on lectin from Gluttonous beauts and their anticancer activities are very limited. In this study, we purified a lectin from hemolymph of G. beauts and identified its molecular weight to be 66kDa. The effect of lectin at different concentrations (μg/mL) on the cell growth and apoptosis were evaluated against MCF-7 and MCF-10A cells, whereas cytotoxicity to the MCF-7 cells mediated by lectin was observed and the mechanism of action of the lectin in including apoptosis in cancer cells via the intrinsic pathway was also proposed. The MCF-7 cells were employed for in vitro studies on cytotoxicity, induction of apoptosis and apoptotic DNA fragmentation. In MCF-10A cells lectin did not show any adverse effect even at higher concentration. Cell cycle analysis also showed a significant cell cycle arrest on selected cells after lectin treatment. Western blotting suggested that lectin up regulates the apoptotic protein expression in MCF-7 cells while it down regulates the level of Bcl-2 expression.

Comparison of two silica based nonviral gene therapy vectors for breast carcinoma: evaluation of the p53 delivery system in Balb/c mice

Abstract Silica nanoparticles as a nonviral vector for in vivo gene therapy neither surface functionalized SiNp1 is neither “a cationic ion” nor a surface (encapsulation) nor SiNp2 (adsorption). p53 gene expression in the breast upon (i.v) administration. SiNp1 showed a 50- and 100-fold transfection activity, tumor growth inhibition, animal survival (80%), and high levels of p53 and Bax were detected in the sera of treated animals compared to SiNp2 or naked pCMV/p53, respectively. These results demonstrate for improvements in the both systems. This study suggests that nonviral vector systems will have important roles in achieving the impermanent gene transfer in vivo.

Biosynthesis of Silver Nanoscale Particles Using Spirulina platensis Induce Growth-Inhibitory Effect on Human Breast Cancer Cell Line MCF-7

A biological method was used to synthesize stable silver nanoparticles that were tested against MCF-7 cells are reported. The structure and percentage of synthesized nanoparticles was characterized by using ultraviolet spectrophotometry, X-Ray diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy methods. The zeta potential value of -36 mV revealed the stability of biosynthesized AgNPs. The in vitro screening of the AgNPs showed potential cytotoxic activity against human breast cancer cell and normal breast epithelial cells the inhibitory concentration (IC50) were found to be 20, 40, 60 and 80 μg/ml for AgNPs against MCF-7 and HBL-100 cells at 24 and 48 h incubation respectively. An induction of apoptosis was evidenced fluorescence microscopy. These results suggest that AgNPs may exert its anti proliferative effects on breast cancer cell line by suppressing its growth, arresting the G0/G1-phase, reducing DNA synthesis.

Targeted Nanotherapeutics Based on Cancer Biomarkers

This chapter aims to provide important combined information in the arena of nanotechnology use in therapeutic nanostructures. The principles of nanotechnological methods of drug delivery are divided into two main branches, including passive targeting, and actively targeted drug delivery. Passive drug delivery has some limitations, such as nonspecific uptake, and toxicity to the normal cells. Hence, the present chapter mainly concentrates on cancer cell-based targeted therapeutic nanostructures. This approach provides a number of advantages, such as increased lifespan, and minimizing nonspecific uptake, as well reducing toxicity to normal cells/tissues. Intriguingly, the development of targeted therapeutic nanostructure approaches based on nanoparticles concerns the identification of specific tumor cell surface biomarkers, and improving the efficacy of the cancer treatment. The main goal of this chapter is to provide collected information on biomarkers-targeted therapeutic nanostructures for cancer nanotherapy.