ROS mediated Cu[Fe(CN)5NO] nanoparticles for triple negative breast cancer: A detailed study in preclinical mouse model.

Triple negative breast cancer (TNBC) is an aggressive form of tumor, more prevalent in younger women resulting in poor survival rate (2nd in cancer deaths) because of its asymptomatic existence. The most popular and convenient approach for the treatment of TNBC is chemotherapy which is associated with several limitations. Considering the importance of nanotechnology in health care system, in the present manuscript, we have designed and developed a simple, efficient, cost effective, and ecofriendly method for the synthesis of copper nitroprusside analogue nanoparticles (Cu[Fe(CN)5NO] which is abbreviated as CuNPANP that may be the potential anti-cancer nanomedicine for the treatment of TNBC. Copper (present in CuNPANP) is used because of its affordability, nutritional value and various biomedical applications. The CuNPANP are thoroughly characterized using several analytical techniques. The in vitro cell viability (in normal cells) and the ex vivo hemolysis assay reveal the biocompatible nature of CuNPANP. The anti-cancer activity of the CuNPANP is established in TNBC cells (MDA-MB-231 and 4T1) through several in vitro assays along with plausible mechanisms. The intraperitoneal administration of CuNPANP in orthotopic breast tumor model by transplanting 4T1 cells into the mammary fat pad of BALB/c mouse significantly inhibits the growth of breast carcinoma as well as increases the survival time of tumor-bearing mice. These results altogether potentiate the anti-cancer efficacy of CuNPANP as a smart therapeutic nanomedicine for treating TNBC in near future after bio-safety evaluation in large animals.

Toxicity study of pro-angiogenic casein manganese oxide nanoparticles: an in vitro and in vivo approach.

Recently, we have demonstrated casein manganese oxide nanoparticles (CMnNP) that exhibit pro-angiogenic property established through different in vitro and in vivo experiments. The CMnNP was explored for therapeutic angiogenesis for treatment of wounds and recovery of hindlimb ischemia in pre-clinical mouse prototypical. It is well known that to translate any therapeutic nanoparticle for future clinical applications, their biosafety evaluation in small and large animals is essential. Herein, in the current study, the biosafety and bioavailability of the CMnNP have been explored by a systematic toxicity profiling study in C57BL/6J mice model. Initially, the in vitro cytotoxic effects of CMnNP were validated in RAW 264.7 cells. Later, the CMnNP was administered intraperitoneally with different doses (50, 300, and 2000 mg/kg b.wt./day) at different time points of exposure (acute: 2 weeks, sub-chronic: 4 weeks as well as chronic exposure: 8 and 20 weeks) with reference to the maximum tolerable dose (MTD) of CMnNP as per the OECD guidelines. The blood hematological and serum biochemical parameters of CMnNP treatment groups indicate negligible changes similar to untreated group. The histopathological examination of CMnNP-treated vital organs (lung, spleen, liver, brain, kidney, and heart) illustrates no major changes even at higher doses. Further, the biodistribution and excretion study depicts normal clearance of CMnNP. Additionally, the serum cytokine levels were normal in the therapeutic dose of CMnNP. The results altogether indicate that the non-toxic nature of CMnNP makes them useful as future therapeutic angiogenic agent for the treatment of various diseases where angiogenesis plays an important role.

Silver nitroprusside nanoparticles for breast cancer therapy: in vitro and in vivo approach.

The advancement of nanotechnology has led to the experimental development of cancer therapeutics, which may overcome the shortcomings of commercially available drugs and facilitate improved clinical outcomes. Recently, several metal nanoparticles, especially silver, have been evaluated by scientists globally as useful chemotherapeutic agents due to their multi-functionality and well-recognized biological activity. Herein, we developed silver nitroprusside nanoparticles (abbreviated as AgNNPs) with slight modifications in the reaction conditions and demonstrated their application for breast cancer therapy using in vitro assays and in vivo experiments in a mouse model. Initially, the modified AgNNPs were thoroughly characterized using several analytical techniques. AgNNPs were found to be biocompatible according to in vitro experiments in normal cell lines (HEK-293 and EA.hy926), which was further validated by a hemolysis assay (ex vivo experiment) using mouse red blood cells. In contrast, the cell viability assay using the MTT reagent showed the cytotoxic nature of the AgNNPs against several cancer cell lines (MDA-MB-231, 4T1, B16F10, and PANC-1). Their detailed anticancer activity was investigated using 4T1 (mouse specific) and MDA-MB-231 (human specific) cells through various in vitro assays. The nanoparticles inhibited the formation of blood vessels in the chick embryo model, highlighting their anti-angiogenic behavior. Furthermore, the administration of AgNNPs significantly inhibited orthotopic breast tumor growth (4T1; BALB/c mice) and increased the survivability of the tumor-bearing mice. Also, we demonstrated the plausible molecular mechanisms for the anti-cancer activity of AgNNPs through various in vitro assays and in vivo experiments. Overall, the results support that AgNNPs can be used as an alternative generalized nanomedicine for the treatment of breast and other cancers after proper biosafety evaluation in near future.

Biosynthesized Silver Nanoparticles for Cancer Therapy and In Vivo Bioimaging.

In the current communication, a simple, environmentally compatible, non-toxic green chemistry process is used for the development of silver nanoparticles (AgZE) by the reaction between silver nitrate (AgNO3) and the ethanolic leaf extract of Zinnia elegans (ZE). The optimization of AgZE is carried out using a series of experiments. Various physico-chemical techniques are utilized to characterize the nanomaterials. The cell viability assay of AgZE in normal cells (CHO, HEK-293T, EA.hy926, and H9c2) shows their biocompatible nature, which is supported by hemolytic assay using mouse RBC. Interestingly, the nanoparticles exhibited cytotoxicity towards different cancer cell lines (U-87, MCF-7, HeLa, PANC-1 and B16F10). The detailed anticancer activity of AgZE on human glioblastoma cell line (U-87) is exhibited through various in vitro assays. In vivo the AgZE illustrates anticancer activity by inhibiting blood vessel formation through CAM assay. Furthermore, the AgZE nanoparticles when intraperitoneally injected in C57BL6/J mice (with and without tumor) exhibit fluorescence properties in the NIR region (excitation: 710 nm, emission: 820 nm) evidenced by bioimaging studies. The AgZE biodistribution through ICPOES analysis illustrates the presence of silver in different vital organs. Considering all the results, AgZE could be useful as a potential cancer therapeutic agent, as well as an NIR based non-invasive imaging tool in near future.

Manganese-based advanced nanoparticles for biomedical applications: future opportunity and challenges.

Nanotechnology is the most promising technology to evolve in the last decade. Recent research has shown that transition metal nanoparticles especially manganese (Mn)-based nanoparticles have great potential for various biomedical applications due to their unique fundamental properties. Therefore, globally, scientists are concentrating on the development of various new manganese-based nanoparticles (size and shape dependent) due to their indispensable utilities. Although numerous reports are available regarding the use of manganese nanoparticles, there is no comprehensive review highlighting the recent development of manganese-based nanomaterials and their potential applications in the area of biomedical sciences. The present review article provides an overall survey on the recent advancement of manganese nanomaterials in biomedical nanotechnology and other fields. Further, the future perspectives and challenges are also discussed to explore the wider application of manganese nanoparticles in the near future. Overall, this review presents a fundamental understanding and the role of manganese in various fields, which will attract a wider spectrum of the scientific community.

Ag2[Fe(CN)5NO]-Fabricated Hydrophobic Cotton as a Potential Wound Healing Dressing: An In Vivo Approach.

There have been reports of different types of wound dressings for various functions and purposes. Cotton being one of the most widely used wound dressing material due to its non-toxic, biodegradable, and other properties is used for fabrication as well as in the form of scaffolds for faster and effective wound closure. Our research team has already demonstrated the role of silver nitroprusside nanoparticles (SNPNPs) for wound healing and antibacterial activity. In the current study, we have developed cotton fabric impregnated with SNPNPs (SNPCFs) which remain photo inert and displayed long-term antimicrobial activity due to the surface modification with the silver nitroprusside complex. These SNPCFs were characterized by various analytical techniques (XRD, FTIR, UV spectroscopy, TGA, TEM, FESEM, EDAX, ICP-OES). The fabricated cotton dressings with nanoparticles showed an improved water contact angle (113-130°) than that of bare cotton gauze (60°) and exhibited more antibacterial property in case of both Gram-negative bacteria (Klebsiella aerogenes and Escherichia coli) and Gram-positive bacteria (Pseudomonas aeruginosa and Bacillus subtilis) even after several washings. The biocompatible nature of SNPCFs was assessed by in vivo chorioallantoic membrane assay that showed no obstruction in the formation of blood vessels. The SNPCFs exhibited better wound healing activity compared to the bare cotton and AgCFs as observed in the C57BL6/J mouse. The histopathological investigation reveals increase in re-epithelialization and deposition of connective tissue. The macrophage (M2) counts in SNPCF-treated skin tissues were supportive of more wound healing activity than mice treated with cotton fabric impregnated with chemically synthesized silver nanoparticles. Based on biodistribution analysis using ICP-OES, the data illustrated that a significant amount of silver is absorbed in the skin tissues of mice as compared to the blood and kidney. Furthermore, the absence of silver from the vital organs (heart, liver, and kidney) corroborates our hypothesis that the SNPCFs can act excellently in treating wounds when topically applied over skin. Thereafter, all these results highlight a strong possibility that SNPCFs exemplify the potential as a new antimicrobial and wound healing agent in future times.

Improved delivery of doxorubicin using rationally designed PEGylated platinum nanoparticles for the treatment of melanoma.

Efficient delivery of chemotherapeutic drugs to tumor cells is one of the crucial issues for modern day cancer therapy. In this article, we report the synthesis of poly ethylene glycol (PEG) assisted colloidal platinum nanoparticles (PtNPs) by borohydride reduction method at room temperature. PtNPs are stable at room temperature for more than 2 years and are stable in serum and phosphate buffer (pH = 7.4) solution for one week. PtNPs show biocompatibility in different normal cell lines (in vitro) and chicken egg embryonic model (ex vivo). Further, we designed and fabricated PtNPs-based drug delivery systems (DDS: PtNPs-DOX) using doxorubicin (DOX), a FDA approved anticancer drug. Various analytical techniques were applied to characterize the nanomaterials (PtNPs) and DDS (PtNPs-DOX). This DDS exhibits inhibition of cancer cell (B16F10 and A549) proliferation, observed by different in vitro assays. PtNPs-DOX induces apoptosis in cancer cells observed by annexin-V staining method. Intraperitoneal (IP) administration of PtNPs-DOX shows substantial reduction of tumor growth in subcutaneous murine melanoma tumor model compared to control group with free drug. Up-regulation of tumor suppressor protein p53 and down regulation of SOX2 and Ki-67 proliferation markers in melanoma tumor tissues (as observed by immunofluorescence and western blot analysis) indicates probable molecular mechanism for the anticancer activity of DDS. Considering the in vitro and pre-clinical (in vivo) results in murine melanoma, it is believed that platinum nanoparticle-based drug delivery formulation could be exploited to develop an alternative therapeutic nanomedicine for cancer therapy in the near future.

Silver Prussian Blue Analogue Nanoparticles: Rationally Designed Advanced Nanomedicine for Multifunctional Biomedical Applications.

The development of simple, cost-effective, and advanced multifunctional technology is the need of the hour to combat cancer as well as bacterial infections. There have been reports of silver nanoparticles (AgNPs), silver salts, and Prussian blue (PB) being used for medicinal purposes which are clinically approved. In this context, in the present communication, we incorporated PB and silver salts (silver nitrate) to develop silver PB analogue nanoparticles (SPBANPs), a new nanomedicine formulation as a safer and effective mode of treatment strategy (2-in-1) for both cancer and bacterial infections. Considering all fundamental issues of nanomedicine, along with understanding of the biological impact of PB, we designed a simple, fast, efficient, cheap, and eco-friendly method for the synthesis of [poly(N-vinyl-2-pyrrolidone)]-stabilized silver hexacyanoferrate nanoparticles (silver PB analogue: Ag3[Fe(CN)6] abbreviated as SPBANPs). Various analytical tools were used to analyze and characterize the nanomaterials (SPBANPs). The SPBANPs were highly stable for several weeks in various phosphate buffers with a range of physiological pH conditions (pH = 6-8). The nanoparticles showed biocompatibility in vivo in C57BL6/J mice that encouraged us to screen the nanoparticles for various biomedical applications. The SPBANPs themselves exhibited remarkable inhibition of cancer cell proliferation (B16F10, A549, MCF-7, and SK-OV-3) in vitro. Substantial inhibition of melanoma tumor growth was observed in the C57BL6/J mouse model (aggressive murine melanoma model: B16F10) after intraperitoneal administration of the SPBANPs without any anticancer drug. Additionally, the SPBANPs exhibited excellent antibacterial activity in various Gram-negative (Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa) and Gram-positive (Bacillus subtilis) bacteria. Interestingly, this nanoformulation itself works as a drug delivery vehicle, as well as an anticancer and antibacterial agent. The in vitro and in vivo results together demonstrate that this biocompatible nanoformulation (SPBANPs) without an anticancer drug or antibiotic could be explored to develop as a multifunctional therapeutic agent (2-in-1) for the treatment of cancer and bacterial infections in the near future.

Recent Development of Metal Nanoparticles for Angiogenesis Study and Their Therapeutic Applications.

Angiogenesis is a crucial biological process of development of blood vessels from pre-existing vasculature, which helps in several physiological functions including embryonic development, hair growth, ovulation, menstruation, tissue repair, and regeneration. Contrastingly, it is also imperative in various pathological conditions like cardiovascular/ischemic diseases, rheumatoid arthritis, cancers, ocular/retinal diseases, and others. These disease conditions are often treated by manipulating angiogenesis using different pro-angiogenic or antiangiogenic factors/molecules through either promoting or inhibiting this complex process, respectively. However, these conventional angiogenic treatment strategies fall short in attaining the desired therapeutic effect due to several limitations including low bioavailability, rapid clearance, high cost, nonspecificity, drug resistance and side effects. Therefore, it is high time for the advancement of different pro- and antiangiogenic materials that could overcome aforesaid limitations, followed by their effective use for the therapy of angiogenesis related diseases. Recently, nanotechnology has drastically advanced in various areas of biology and medicine including therapeutic angiogenesis. Globally, many research groups including ours explored various inorganic metal nanomaterials that could efficiently manipulate the angiogenesis process either by augmenting or inhibiting it. The extensive investigation of the mechanisms underlying nanomaterials-mediated manipulation of angiogenesis is also well-documented. In the present review article, we intend to introduce the recent developments of inorganic nanomedicine manipulating angiogenesis with major focus on pro-angiogenic nanomaterials and their therapeutic applications along with associated challenges and future directions.

Biosynthesized Gold Nanoparticles: In Vivo Study of Near-Infrared Fluorescence (NIR)-Based Bio-imaging and Cell Labeling Applications.

Near infrared (NIR) fluorescence imaging is a striking imaging modality for biomedical and clinical applications due to its deep tissue penetration and low phototoxicity. The major issue with NIR dyes is their non-specific distribution and requirement of tagging with biomolecules for specific tissue localization. Till now, there have been no imaging agents available that can distribute into a specific organ without the need for targeted ligands, which remains as an unmet clinical need. In the present study, we demonstrate that the Zinnia elegans plant extract (abbreviated as ZE) assisted synthesis of highly biocompatible gold nanoparticles (AuZE), leading to their non-invasive bio-imaging applications in the NIR region (red at 820 nm emission: NIR region). AuZE and ZE both exhibited green fluorescence at 350 nm excitation and red fluorescence in the NIR region (710 nm). We verified the source of this fluorescence, which originates from the fluorescent molecules present in the ZE extract. After intraperitoneal administration in C57BL6 mice, very interestingly, AuZE is distributed into the brain of C57BL6 mice without the need for any targeted ligand and exhibited bright red fluorescence in the NIR region (710 nm excitation, 820 nm emission) as evidenced by non-invasive imaging as well as ICPOES techniques. We further explored the activity of ZE and AuZE as cell labeling agents (B16F10 cells were pre-incubated with AuZE and implanted into mice, and the fluorescence was monitored), which could be applicable for graft transplantation biology. To the best of our knowledge, this is the first report that demonstrates the versatile applications of green synthesized gold nanoparticles using a ZE extract. Considering these exciting results and fruitful outcomes, the ZE and AuZE NPs would stand as an alternative imaging agent to commercially available NIR dyes and change the conventional fluorescence-based bio-imaging strategies. Therefore, the biosynthesized AuNPs open new directions for future research to explore these latest observations in the field of disease diagnosis and therapy.