Manoj Saxena

Bio: Manoj Saxena is an academic researcher from University of Puerto Rico, Río Piedras. The author has contributed to research in topics: Conjugate & Apoptosis. The author has an hindex of 6, co-authored 11 publications receiving 150 citations. Previous affiliations of Manoj Saxena include University of Puerto Rico & Birkbeck, University of London.

Unusual Synergism of Transferrin and Citrate in the Regulation of Ti(IV) Speciation, Transport, and Toxicity.

Abstract: Human serum transferrin (sTf) is a protein that mediates the transport of iron from blood to cells. Assisted by the synergistic anion carbonate, sTf transports Fe(III) by binding the metal ion in a closed conformation. Previous studies suggest sTf’s role as a potential transporter of other metals such as titanium. Ti is a widely used metal in colorants, foods, and implants. A substantial amount of Ti is leached into blood from these implants. However, the fate of the leached Ti and its transport into the cells is not known. Understanding Ti interaction with sTf assumes a greater significance with our ever increasing exposure to Ti in the form of implants. On the basis of in vitro studies, it was speculated that transferrin can bind Ti(IV) assisted by a synergistic anion. However, the role and identity of the synergistic anion(s) and the conformational state in which sTf binds Ti(IV) are not known. Here we have solved the first X-ray crystal structure of a Ti(IV)-bound sTf. We find that sTf binds Ti(IV) in...

Fueling a Hot Debate on the Application of TiO2 Nanoparticles in Sunscreen.

Abstract: Titanium is one of the most abundant elements in the earth’s crust and while there are many examples of its bioactive properties and use by living organisms, there are few studies that have probed its biochemical reactivity in physiological environments. In the cosmetic industry, TiO2 nanoparticles are widely used. They are often incorporated in sunscreens as inorganic physical sun blockers, taking advantage of their semiconducting property, which facilitates absorbing ultraviolet (UV) radiation. Sunscreens are formulated to protect human skin from the redox activity of the TiO2 nanoparticles (NPs) and are mass-marketed as safe for people and the environment. By closely examining the biological use of TiO2 and the influence of biomolecules on its stability and solubility, we reassess the reactivity of the material in the presence and absence of UV energy. We also consider the alarming impact that TiO2 NP seepage into bodies of water can cause to the environment and aquatic life, and the effect that it can have on human skin and health, in general, especially if it penetrates into the human body and the bloodstream.

Inducing cell death in vitro in cancer cells by targeted delivery of cytochrome c via a transferrin conjugate.

Abstract: One of the major drawbacks of many of the currently used cancer drugs are off-target effects. Targeted delivery is one method to minimize such unwanted and detrimental events. To actively target lung cancer cells, we have developed a conjugate of the apoptosis inducing protein cytochrome c with transferrin because the transferrin receptor is overexpressed by many rapidly dividing cancer cells. Cytochrome c and transferrin were cross-linked with a redox sensitive disulfide bond for the intra-cellular release of the protein upon endocytosis by the transferrin receptor. Confocal results demonstrated the cellular uptake of the cytochrome c-transferrin conjugate by transferrin receptor overexpressing A549 lung cancer cells. Localization studies further validated that this conjugate escaped the endosome. Additionally, an in vitro assay showed that the conjugate could induce apoptosis by activating caspase-3. The neo-conjugate not only maintained an IC50 value similar to the well known drug cisplatin (50 μM) in A549 cancer cells but also was nontoxic to the normal lung (MRC5) cells. Our neo-conjugate holds promise for future development to target cancers with enhanced transferrin receptor expression.

A ubiquitous metal, difficult to track: towards an understanding of the regulation of titanium(IV) in humans

Abstract: Despite the ubiquitous nature of titanium(iv) and several examples of its beneficial behavior in different organisms, the metal remains underappreciated in biology. There is little understanding of how the metal might play an important function in the human body. Nonetheless, a new insight is obtained regarding the molecular mechanisms that regulate the blood speciation of the metal to maintain it in a nontoxic and potentially bioavailable form for use in the body. This review surveys the literature on Ti(iv) application in prosthetics and in the development of anticancer therapeutics to gain an insight into soluble Ti(iv) influx in the body and its long-term impact. The limitation in analytical tools makes it difficult to depict the full picture of how Ti(iv) is transported and distributed throughout the body. An improved understanding of Ti function and its interaction with biomolecules will be helpful in developing future technologies for its imaging in the body.

Binary titanium alloys as dental implant materials-a review.

Abstract: Titanium (Ti) has been used for long in dentistry and medicine for implant purpose During the years, not only the commercially pure Ti but also some alloys such as binary and tertiary Ti alloys were used The aim of this review is to describe and compare the current literature on binary Ti alloys, including Ti-Zr, Ti-In, Ti-Ag, Ti-Cu, Ti-Au, Ti-Pd, Ti-Nb, Ti-Mn, Ti-Mo, Ti-Cr, Ti-Co, Ti-Sn, Ti-Ge and Ti-Ga, in particular to mechanical, chemical and biological parameters related to implant application Literature was searched using the PubMed and Web of Science databases, as well as google without limiting the year, but with principle key terms such as ' Ti alloy', 'binary Ti ', 'Ti-X' (with X is the alloy element), 'dental implant' and 'medical implant' Only laboratory studies that intentionally for implant or biomedical applications were included According to available literatures, we might conclude that most of the binary Ti alloys with alloying <20% elements of Zr, In, Ag, Cu, Au, Pd, Nb, Mn, Cr, Mo, Sn and Co have high potential as implant materials, due to good mechanical performance without compromising the biocompatibility and biological behaviour compare to cp-Ti

Development of L-Asparaginase Biobetters: Current Research Status and Review of the Desirable Quality Profiles

Abstract: L-Asparaginase (ASNase) is a vital component of the first line treatment of acute lymphoblastic leukemia (ALL), an aggressive type of blood cancer expected to afflict over 53,000 people worldwide by 2020. More recently, ASNase has also been shown to have potential for preventing metastasis from solid tumors. The ASNase treatment is, however, characterized by a plethora of potential side effects, ranging from immune reactions to severe toxicity. Consequently, in accordance with Quality-by-Design (QbD) principles, ingenious new products tailored to minimize adverse reactions while increasing patient survival have been devised. In the following pages, the reader is invited for a brief discussion on the most recent developments in this field. Firstly, the review presents an outline of the recent improvements on the manufacturing and formulation processes, which can severely influence important aspects of the product quality profile, such as contamination, aggregation and enzymatic activity. Following, the most recent advances in protein engineering applied to the development of biobetter ASNases (i.e., with reduced glutaminase activity, proteolysis resistant and less immunogenic) using techniques such as site-directed mutagenesis, molecular dynamics, PEGylation, PASylation and bioconjugation are discussed. Afterwards, the attention is shifted toward nanomedicine including technologies such as encapsulation and immobilization, which aim at improving ASNase pharmacokinetics. Besides discussing the results of the most innovative and representative academic research, the review provides an overview of the products already available on the market or in the latest stages of development. With this, the review is intended to provide a solid background for the current product development and underpin the discussions on the target quality profile of future ASNase-based pharmaceuticals.