Soundarapandian Kannan

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.

Fabrication of a pH responsive DOX conjugated PEGylated palladium nanoparticle mediated drug delivery system: an in vitro and in vivo evaluation

Efficient delivery of therapeutics into tumor cells to increase the intracellular drug concentration is one of the key issues in cancer therapy. In this work, we designed pH responsive PEGylated palladium nanoparticles (PdNPs) as an anticancer drug nanocarrier system for effective drug delivery. The synthesis of the nanocarrier involved conjugation of doxorubicin (DOX) to the surface of PEGylated PdNPs via a hydrazone interaction. The nanoparticles were characterized by UV-spectroscopy, Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), zeta potential, Fourier transmission Infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and Nuclear Magnetic Resonance (NMR). The drug release behavior was subsequently studied at different pH conditions. The results showed a sustained release of DOX preferentially at the desired endosomal pH (5.5). The biological activity of the DOX conjugated PEGylated PdNPs was studied by an MTT assay, fluorescence microscopy, and apoptosis. Intracellular-uptake studies revealed preferential uptake of these NPs into HeLa cancer cells. The in vitro apoptosis study revealed that the DOX conjugated PEGylated PdNPs caused significant death to the HeLa cells. Further, blank PEGylated PdNPs displayed low toxicity and good biocompatibility. DOX conjugated PEGylated PdNPs had the strongest anti-tumor efficacy against HeLa tumor xenograft models in vivo. These findings demonstrated that PEGylated PdNPs were deemed as a potential drug nanocarrier for cancer therapy.

Synergistic effect of chemo-photothermal for breast cancer therapy using folic acid (FA) modified zinc oxide nanosheet.

Modern therapies for malignant breast cancer in clinics are not efficacious and often result in deprived patient compliance owing to squat therapeutic effectiveness and strong systemic side effects. In order to overcome this, we combined chemo-photothermal targeted therapy of breast cancer within one novel multifunctional drug delivery system. Folic Acid-functionalized polyethylene glycol coated Zinc Oxide nanosheet (FA-PEG-ZnO NS), was successfully synthesized, characterized and introduced to the drug delivery field for the first time. A doxorubicin (DOX)-loaded FA-PEG-ZnO NS based system (DOX-FA-PEG-ZnO NS) showed stimulative effect of heat, pH responsive and sustained drug release properties. Cytotoxicity experiments confirmed that combined therapy mediated the maximum rate of death in breast cancer cells compared to that of single chemotherapy or photothermal therapy. In vivo toxicity evaluation showed that the DOX-FA-PEG-ZnO NS contains minimum systemic toxicity in the mice model system. The findings of the present study provided an ideal drug delivery system for breast cancer therapy due to the advanced chemo-photothermal synergistic targeted therapy and good drug release properties of DOX-FA-PEG-ZnO NS, which could effectively avoid frequent and invasive dosing and improve patient compliance. Thus, functionalized-ZnO NS could be used as a novel nanomaterial for selective chemo-photothermal therapy.

Fabrication of divalent ion substituted hydroxyapatite/gelatin nanocomposite coating on electron beam treated titanium: mechanical, anticorrosive, antibacterial and bioactive evaluations

The key property in the fabrication of a biomaterial is to facilitate the replacement and/or regeneration of damaged tissues and organs. To obtain such a biomaterial, we fabricated a triple mineral (strontium, magnesium and zinc) substituted hydroxyapatite/gelatin (M-HAP/Gel) nanocomposite coating on electron beam treated titanium (Ti) metal. The influence of gelatin concentration in M-HAP was studied to investigate its effect on morphological changes, crystallinity, mechanical and anticorrosion properties. The M-HAP/Gel nanocomposite coating (with 3 wt% gelatin) on treated Ti resulted in better mechanical and anticorrosion properties as a consequence of the electron beam treatment of Ti. A reduced number of bacterial colonies were observed for the M-HAP/Gel composite against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) microbes which evidences a lower chance of implant failure after implantation. Moreover, the cell proliferation assay, live/dead staining of MT3C3-E1 cells and cell viability of fibroblast stem cells on the resultant nanocomposite revealed that the M-HAP/Gel composite will definitely be an effective implant material for better cell growth in orthopedic applications.

Fabrication of Minerals Substituted Porous Hydroxyapaptite/Poly(3,4-ethylenedioxy pyrrole-co-3,4-ethylenedioxythiophene) Bilayer Coatings on Surgical Grade Stainless Steel and Its Antibacterial and Biological Activities for Orthopedic Applications

Current strategies of bilayer technology have been aimed mainly at the enhancement of bioactivity, mechanical property and corrosion resistance. In the present investigation, the electropolymerization of poly(3,4-ethylenedioxypyrrole-co-3,4-ethylenedioxythiophene) (P(EDOP-co-EDOT)) with various feed ratios of EDOP/EDOT on surgical grade stainless steel (316L SS) and the successive electrodeposition of strontium (Sr(2+)), magnesium (Mg(2+)) and cerium (Ce(3+)) (with 0.05, 0.075 and 0.1 M Ce(3+)) substituted porous hydroxyapatite (M-HA) are successfully combined to produce the bioactive and corrosion resistance P(EDOP-co-EDOT)/M-HA bilayer coatings for orthopedic applications. The existence of as-developed coatings was confirmed by Fourier transform-infrared spectroscopy (FT-IR), X-ray diffraction (XRD), proton nuclear magnetic resonance spectroscopy ((1)H NMR), high resolution scanning electron microscopy (HRSEM), energy dispersive X-ray analysis (EDAX) and atomic force microscopy (AFM). Also, the mechanical and thermal behavior of the bilayer coatings were analyzed. The corrosion resistance of the as-developed coatings and also the influence of copolymer (EDOP:EDOT) feed ratio were studied in Ringers solution by electrochemical techniques. The as-obtained results are in accord with those obtained from the chemical analysis using inductively coupled plasma atomic emission spectrometry (ICP-AES). In addition, the antibacterial activity, in vitro bioactivity, cell viability and cell adhesion tests were performed to substantiate the biocompatibility of P(EDOP-co-EDOT)/M-HA bilayer coatings. On account of these investigations, it is proved that the as-developed bilayer coatings exhibit superior bioactivity and improved corrosion resistance over 316L SS, which is potential for orthopedic applications.

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.

A correlation of fecal volatiles and steroid hormone profiles with behavioral expression during estrous cycle of goat, Capra hircus

Chemical signals (both volatile and non-volatile) form the major communication channels in animals. These signals are transferred mainly through excretory sources to facilitate inter-individual communication. In particular, the reproductive cycle of female mammals, including goats, exhibits significant changes in the constituents of their excretory products, and female mammals also express different behavioral patterns. We propose that feces is one of the important sources of chemo-signals in goats. However, the behavioral patterns and analysis of excretory sources based on chemical communication have not yet been studied in the Indian goat, Capra hircus. To validate our hypothesis, we analyzed the behavioral patterns and the volatiles and steroid hormone profiles in the feces samples of female goats during the estrous cycle. Here, we synchronized the estrous cycle in six female goats and obtained feces samples. The samples were extracted with dichloromethane and analyzed using gas chromatography-mass spectrometry. A portion of the sample was used for hormone assay to confirm the phases in the estrous cycle. Induction of she-goats into estrus was detected from the vaginal swelling, mucus discharge, restlessness, reduced milk secretion, bellowing, bleating, frequent urination, standing heat, allowing the male to mount, mounting on other females and teasing of males. The repeated male behaviors viz., flehmen, mounting, penile protrusion, body rubbing, dominance over other males and finally coitus with estrus female by male goats were observed. Analysis of volatiles revealed a total of twenty-four compounds combining all the phases in the estrous cycle. Among those, some of the volatile compounds and two antioxidants (ascorbic acid and vitamin E) were estrus-specific. Based on the fecal steroid analysis, higher level of estradiol during estrus and higher level of progesterone during post-estrus were observed. The behavioral patterns of female and male goats combined with qualitative differences in the volatile compounds and the two antioxidants rendered the estrus identifiable. Furthermore, the fecal steroid analysis also supported the detection of hormonal status during the estrous cycle. To the best of our knowledge, this is the first report correlating the behavior with volatiles and hormones in the feces samples from female Indian goats. It is concluded that the volatile pattern and hormone profile in feces, supported by specific behavioral patterns, should be considered a better modality of non-invasive estrus detection in goats.

Smart rose flower like bioceramic/metal oxide dual layer coating with enhanced anti-bacterial, anti-cancer, anti-corrosive and biocompatible properties for improved orthopedic applications

Metallic implants suffer from numerous problems such as stress shielding, poor prolonged osseointegration and corrosion under in vivo environments. Such problems are often faced by bone cancer patients as they receive orthopedic implants after cancerous bone resection. Unfortunately, there are no orthopedic materials developed so far that simultaneously increase healthy bone growth as takes place in traditional orthopedic implant applications, while inhibiting cancerous bone growth. Based on these issues, the long-term objective of this study was to introduce a new implant material in an integrated way. Hence we have fabricated a selenium (Se), and manganese (Mn) substituted flower like hydroxyapatite (HAP) coating on zirconium oxide (ZrO2) coated AZ91 magnesium alloy. The flower like Se,Mn-HAP/ZrO2 dual layer coating on the AZ91 magnesium alloy was characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), high-resolution scanning electron microscopy (HRSEM) and energy dispersive X-ray (EDX) analysis. Also, the mechanical properties of the dual layer coating were evaluated using adhesion and Vickers micro-hardness tests. The effect of the dual layer coating on the corrosion behavior of the AZ91 magnesium alloy was also investigated in simulated body fluid (SBF) using electrochemical studies. The cell–material interaction of the dual layer coating was observed in vitro with human osteosarcoma MG63 cells for cell proliferation at 1, 4 and 7 days of incubation and in vivo in Wistar rats for 14 and 28 days of implantation. From the results it was found that the dual layer coated AZ91 Mg alloy has an optimal structure and morphology, as indicated by SEM, showing a desired surface for the osteoblast adhesion, viability and proliferation. The new ceramic coating has induced an increased adhesion strength and microhardness, improved corrosion resistance, enhanced osteoblast proliferation and inhibited the growth of cancerous cells. Therefore, based on these results, we propose a new dual layer coated AZ91 Mg alloy which satisfies the requirements in bone cancer treatment and signifies progress in the field of implant materials.

Bioformulation of silver nanoparticles as berberine carrier cum anticancer agent against breast cancer

Development of a nano-drug cum nano-carrier in a single platform seems to be conquered by almost a missionary fanaticism towards unraveling more and more about the bioavailability and anticancer activity at the molecular level. The present work mainly focuses on the bioformulation of silver nanoparticles (AgNPs) as a carrier for berberine (BBR) and tests whether biogenic AgNPs elicit anticancer activity against breast cancer. Biogenic AgNPs and BBR loaded AgNPs are identified and characterized by spectroscopic and microscopic analysis. BBR tethers AgNPs through electrostatic interaction. The current investigation proves that the BBR loaded AgNP complex exhibits a dose-dependent cytotoxicity against MCF-7 and MDA-MB-231 breast cancer cell lines. Obviously, AO/EtBr and DAPI staining evidenced an induction of apoptosis. Meanwhile, western blot analysis suggested that BBR loaded AgNPs persuaded the activation of p53 and Bax by down regulating Bcl-2 expression. The in vivo study further encourages our in vitro data that showed a significant suppression of tumor growth and insignificant toxicity in vital organs. Hemolysis assay and histopathological studies confirmed the biocompatibility of the BBR loaded AgNPs. Altogether, our findings demonstrated that BBR could be easily loaded to biogenic AgNPs and can serve as a potential anticancer agent for breast cancer.