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ABSTRACT: Biomedical nanotechnology is an evolving field having enormous potential to positively impact the health care system. Important biomedical applications of nanotechnology that may have potential clinical applications include targeted drug delivery, detection/diagnosis and imaging. Basic understanding of how nanomaterials, the building blocks of nanotechnology, interact with the cells and their biological consequences are beginning to evolve. Noble metal nanoparticles such as gold, silver and platinum are particularly interesting due to their size and shape dependent unique optoelectronic properties. These noble metal nanoparticles, particularly of gold, have elicited a lot of interest for important biomedical applications because of their ease of synthesis, characterization and surface functionalization. Furthermore, recent investigations are demonstrating another promising application of these nanomaterials as self-therapeutics. To realize the potential promise of these unique inorganic nanomaterials for future clinical translation, it is of utmost importance to understand a few critical parameters; (i) how these nanomaterials interact with the cells at the molecular level; (ii) how their biodistribution and pharmacokinetics influenced by their surface and routes of administration; (iii) mechanism of their detoxification and clearance and (iv) their therapeutic efficacy in appropriate disease model. Thus in this critical review, we will discuss the various clinical applications of gold, silver and platinum nanoparticles with relevance to above parameters. We will also mention various routes of synthesis of these noble metal nanoparticles. However, before we discuss present research, we will also look into the past. We need to understand the discoveries made before us in order to further our knowledge and technological development (318 references).
Chemical Society Reviews 03/2012; 41(7):2943-70. · 28.76 Impact Factor
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ABSTRACT: Gold nanoparticles can be used as a scaffold to elucidate the mechanism of endocytosis of cetuximab and its nanoconjugates, as well as the switching of endocytic pathways (caveolar versus pinocytotic) in pancreatic cancer cells, as demonstrated by P. Mukherjee and co-workers in their Communication (DOI: 10.1002/anie.201105432). Tailoring the mechanism of endocytosis may be useful for targeting specific intracellular pathways to minimize the side effects of pharmaceutical compounds.
Angewandte Chemie International Edition 12/2011; · 13.45 Impact Factor
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ABSTRACT: On the right path: The mechanisms of endocytosis of cetuximab (C225) and its nanoconjugates have been elucidated in a pancreatic cancer cell line. By using gold nanoparticles as a scaffold, it is possible to switch the pathway for endocytosis from a Dyn-2-dependent caveolar mechanism to Cdc42-dependent pinocytosis/phagocytosis. Tailoring endocytotic mechanisms may enable specific intracellular pathways to be targeted.
Angewandte Chemie International Edition 12/2011; 51(7):1563-7. · 13.45 Impact Factor
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Advanced Materials 11/2011; 23(43):5034-8. · 13.88 Impact Factor
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ABSTRACT: A simple synthesis of a targeted drug delivery system with enhanced cytotoxicity to (epidermal growth factor receptor) EGFR(+) cancer cells.
Chemical Communications 06/2011; 47(30):8530-2. · 6.17 Impact Factor
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ABSTRACT: Nanotechnology is an evolving field with enormous potential for biomedical applications. The growing interest to use inorganic nanoparticles in medicine is due to the unique size- and shape-dependent optoelectronic properties. Herein, we will focus on gold, silver and platinum nanoparticles, discussing recent developments for therapeutic applications with regard to cancer in terms of nanoparticles being used as a delivery vehicle as well as therapeutic agents. We will also discuss some of the key challenges to be addressed in future studies.
Pharmaceutical Research 02/2011; 28(2):237-59. · 4.09 Impact Factor
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ABSTRACT: Undoubtedly ovarian cancer is a vexing, incurable disease for patients with recurrent cancer and therapeutic options are limited. Although the polycomb group gene, Bmi-1 that regulates the self-renewal of normal stem and progenitor cells has been implicated in the pathogenesis of many human malignancies, yet a role for Bmi-1 in influencing chemotherapy response has not been addressed before. Here we demonstrate that silencing Bmi-1 reduces intracellular GSH levels and thereby sensitizes chemoresistant ovarian cancer cells to chemotherapeutics such as cisplatin. By exacerbating ROS production in response to cisplatin, Bmi-1 silencing activates the DNA damage response pathway, caspases and cleaves PARP resulting in the induction apoptosis in ovarian cancer cells. In an in vivo orthotopic mouse model of chemoresistant ovarian cancer, knockdown of Bmi-1 by nanoliposomal delivery significantly inhibits tumor growth. While cisplatin monotherapy was inactive, combination of Bmi-1 silencing along with cisplatin almost completely abrogated ovarian tumor growth. Collectively these findings establish Bmi-1 as an important new target for therapy in chemoresistant ovarian cancer.
PLoS ONE 01/2011; 6(3):e17918. · 4.09 Impact Factor
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ABSTRACT: Treatment with monoclonal antibody (mAbs) is a viable therapeutic option in cancer. Recently, these mAbs such as cetuximab, herceptin, etc., have been used as targeting agents to selectively deliver chemotherapeutics to cancerous cells. However, mechanisms of nanoparticles-mAbs interactions with the target cells and its effect on intracellular trafficking and mechanism are currently unknown. In this paper, we demonstrate that the distinct patterning and dynamics of anti-EGFR (epidermal growth factor receptor) antibody cetuximab (C225)- induced EGFR internalization in pancreatic cancer cells with variable receptor expression is altered upon nanoconjugation. Nanoconjugation uniformly enhanced C225-induced EGFR endocytosis in PANC-1, AsPC-1, and MiaPaca-2 cells, influenced its compartmentalization and regulated the involvement of dynamin-2 in the endocytic processes. Receptor endocytosis and its intracellular trafficking were monitored by confocal microscopy and transmission electron microscopy. The role of dynamin-2 in EGFR endocytosis was determined after overexpressing either wild-type dynamin-2 or mutant dynamin-2 in pancreatic cancer cells followed by tracking the receptor-antibody complex internalization by confocal microscopy. Significantly, these findings demonstrate that the nanoconjugation cannot be construed as an innocuous reaction involved in attaching the targeting agent to the nanoparticle, instead it may distinctly alter the cellular processes at the molecular level, at least antibody induced receptor endocytosis. This information is critical for successful design of a nanoparticle-based targeted drug delivery system for future clinical translation.
Proceedings of the National Academy of Sciences 08/2010; 107(33):14541-6. · 9.68 Impact Factor
