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Vedagopuram Sreekanth

Bio: Vedagopuram Sreekanth is an academic researcher from Harvard University. The author has contributed to research in topics: Bile acid & Lithocholic acid. The author has an hindex of 11, co-authored 22 publications receiving 267 citations. Previous affiliations of Vedagopuram Sreekanth include Brigham and Women's Hospital & Manipal University.

Papers
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Journal ArticleDOI
TL;DR: It is noticed that DOX-Gel nanocarriers are especially effective when injected during the early stage of tumor progression, and achieve a substantial decrease in tumor load in the long term.
Abstract: The majority of the localized drug delivery systems are based on polymeric or polypeptide scaffolds, as weak intermolecular interactions of low molecular weight hydrogelators (LMHGs, Mw <500 Da) are significantly perturbed in the presence of anticancer drugs. Here, we present l-alanine derived low molecular weight hydrogelators (LMHGs) that remain injectable even after entrapping the anticancer drug doxorubicin (DOX). These DOX containing nanoassemblies (DOX-Gel) showed promising anticancer activity in mice models. Subcutaneous injection of DOX-Gel near the tumor achieved a greater decrease in tumour load than by intravenous injection of DOX (DOX-IV), and local injection of DOX alone (DOX-Local) at the tumor site. We noticed that DOX-Gel nanocarriers are especially effective when injected during the early stage of tumor progression, and achieve a substantial decrease in tumor load in the long term.

74 citations

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TL;DR: These studies showed that bile acids provide a new scaffold for high drug loading and that their anticancer activities strongly depend on charge and hydrophobicity of lipid-drug conjugates.

40 citations

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TL;DR: In this paper, site-specific and multiple-site conjugation of a wide assortment of molecules on both the termini and internal sites of Cas9, creating a platform for endowing Cas9 with diverse functions, using this platform, Cas9 can be modified to more precisely incorporate exogenously supplied singlestranded oligonucleotide donor (ssODN) at the DNA break site.
Abstract: Genetically fusing protein domains to Cas9 has yielded several transformative technologies; however, the genetic modifications are limited to natural polypeptide chains at the Cas9 termini, which excludes a diverse array of molecules useful for gene editing. Here, we report chemical modifications that allow site-specific and multiple-site conjugation of a wide assortment of molecules on both the termini and internal sites of Cas9, creating a platform for endowing Cas9 with diverse functions. Using this platform, Cas9 can be modified to more precisely incorporate exogenously supplied single-stranded oligonucleotide donor (ssODN) at the DNA break site. We demonstrate that the multiple-site conjugation of ssODN to Cas9 significantly increases the efficiency of precision genome editing, and such a platform is compatible with ssODNs of diverse lengths. By leveraging the conjugation platform, we successfully engineer INS-1E, a β-cell line, to repurpose the insulin secretion machinery, which enables the glucose-dependent secretion of protective immunomodulatory factor interleukin-10. Cas9 fusions partners are often limited to natural polypeptide chains at the Cas9 termni. Here the authors present a platform for site-specific and multiple-site conjugation to both termini and internal sites of Cas9, and they apply this platform to efficiently engineer insulin-producing β cells.

29 citations

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TL;DR: Structural modification of the scaffold with library of a wide variety of substituents may lead to the development of novel selective anti-cancer agents in the future.

25 citations

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TL;DR: It is presented a new concept that fine-tuning of the charged head group modulates the specificity of amphiphiles against bacterial membranes to design more specific and potent antimycobacterial agents.
Abstract: Tuberculosis faces major challenges for its cure due to (a) long treatment period, (b) emergence of drug resistance bacteria, and (c) poor patient compliance. Disrupting the membrane integrity of mycobacteria as a therapeutic strategy has not been explored well as the rigid, waxy, and hydrophobic nature of mycobacterial lipids does not allow binding and penetration of charged amtimicrobial amphiphiles and peptides. Here, we present a new concept that fine-tuning of the charged head group modulates the specificity of amphiphiles against bacterial membranes. We show that hard-charged amphiphiles interact with mycobacterial trehalose dimycolates and penetrate through rigid mycobacterial membranes. In contrast, soft-charged amphiphiles specifically inhibit the growth of both E. coli and S. aureus via electrostatic interactions. These subtle variations between interactions of amphiphiles and bacterial membranes could be explored further to design more specific and potent antimycobacterial agents.

24 citations


Cited by
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Journal ArticleDOI
TL;DR: Generally, injectable hydrogel-based drug delivery systems are found to be more efficacious than the conventional systemic chemotherapy in terms of cancer treatment.

284 citations

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TL;DR: The present article describes the structural, chemical, and biological features of imidazoles, an aromatic diazole and alkaloid with anticancer properties, which are available on the market.
Abstract: Cancer is a black spot on the face of humanity in this era of science and technology. Presently, several classes of anticancer drugs are available in the market, but issues such as toxicity, low efficacy and solubility have decreased the overall therapeutic indices. Thus, the search for new promising anticancer agents continues, and the battle against cancer is far from over. Imidazole is an aromatic diazole and alkaloid with anticancer properties. There is considerable interest among scientists in developing imidazoles as safe alternatives to anticancer chemotherapy. The present article describes the structural, chemical, and biological features of imidazoles. Several classes of imidazoles as anticancer agents based on their mode of action have been critically discussed. A careful observation has been made into pharmacologically active imidazoles with better or equal therapeutic effects compared to well-known imidazole-based anticancer drugs, which are available on the market. A brief discussion of the toxicities of imidazoles has been made. Finally, the current challenges and future perspectives of imidazole based anticancer drug development are conferred.

213 citations

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TL;DR: This review covers the main research published between early 2013 to mid-2015 and takes into account several previous reviews on the subject, with particular attention given to anticancer hybrids.
Abstract: Introduction: The hybridization of biologically active molecules is a powerful tool for drug discovery used to target a variety of diseases. It offers the prospect of better drugs for the treatment of a number of illnesses including cancer, malaria, tuberculosis and AIDS. Hybrid drugs can provide combination therapies in a single multi-functional agent and, by doing so, be more specific and powerful than conventional classic treatments. This research field is in great expansion and attracts many researchers worldwide.Area covered: This review covers the main research published between early 2013 to mid-2015 and takes into account several previous reviews on the subject. Its intention is to showcase the most recent advances reported towards the development of molecular hybrids in drug discovery. Particular attention is given to anticancer hybrids throughout the review.Expert opinion: Current advances show that molecular hybrids of biologically active molecules can lead to powerful therapeutics. Nat...

197 citations

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TL;DR: The lipid moiety in the conjugates can significantly enhance drug loading into hydrophobic components of delivery carriers and thus generate formulations with high drug loading and superior stability.
Abstract: Lipid–drug conjugates (LDCs) are drug molecules that have been covalently modified with lipids. The conjugation of lipids to drug molecules increases lipophilicity and also changes other properties of drugs. The conjugates demonstrate several advantages including improved oral bioavailability, improved targeting to the lymphatic system, enhanced tumor targeting, and reduced toxicity. Based on the chemical nature of drugs and lipids, various conjugation strategies and chemical linkers can be utilized to synthesize LDCs. Linkers and/or conjugation methods determine how drugs are released from LDCs and are critical for the optimal performance of LDCs. In this review, different lipids used for preparing LDCs and various conjugation strategies are summarized. Although LDCs can be administered without a delivery carrier, most of them are loaded into appropriate delivery systems. The lipid moiety in the conjugates can significantly enhance drug loading into hydrophobic components of delivery carriers and thus ge...

195 citations

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TL;DR: An overview on hydrogels loaded with anticancer drugs for the treatment of GBM recently used in preclinical and clinical studies, their advantages and major limitations for clinical translation is provided.

170 citations