- Email: [email protected]
Nanotechnology helps medicine: Nanoscale swimmers and their future applications
198 migration [3]. Due to the inherent ability to utilize the nucleotides and nucleosides as substrate autotaxin(E-NPP2) act as a positive regulator by terminating P2X and P2Y receptor signalling coupled to Ca2+-influx, Gi, Gs and Gq proteins [4]. LPC is a free or membrane bound form of lipid(s) which are converted to arachidonic acid (AA) by membrane bound phospholipase C and A2. AA is a substrate for the lipoxygenase pathway forming LTB4 (Leukotriene B4). LTB4 has been hypothesized as an essential metabolic intermediate in the extracellular nucleotide-induced overexpression of integrins [5]. In the context of the proposed hypotheses, it is essential to point out that both LPC-mediated signaling and extracellular nucleotide-induced signaling transpire via LTB4-mediated events converging on the mitogen activated protein kinases (MAPK) pathway. It is suggested that it is a cumulative effect that mediate the overexpression of the integrin(s) on the neutrophil membrane. Specific type of integrins has also been shown to mediate the signaling cascade via PI3Kinase, followed by one or more pathways converging on MAPKs for activation and secretion of autotaxin [6]. In summary, the ATX extracellularly attenuate the purine/pyrimidine signaling, but exacerbate inflammation by upregulating the integrins on neutrophil membrane via LTB4 for augmenting chemotaxis.
Correspondence
References [1] Clair T, Lee HY, Liotta LA, Stracke ML. Autotaxin is an exoenzyme possessing 50 -nucleotide phosphodiesterase/ATP pyrophosphatase and ATPase activities. J Biol Chem 1997;272:996–1001. [2] Tokumura A, Majima E, Kariya Y, Tominaga K, Kogure K, Yasuda K et al. Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase. J Biol Chem 2002;277:39436–42. [3] Mills GB, Moolenaar WH. The emerging role of lysophosphatidic acid in cancer. Nat Rev Cancer 2003;8:582–91. [4] Goding JW, Grobben B, Slegers H. Physiological and pathophysiological functions of the ecto-nucleotide pyrophosphatase/phosphodiesterase family. Biochim Biophys Acta 2003;1638:1–19. [5] Kannan S. Neutrophil chemotaxis: potential role of chemokine receptors in extracellular nucleotide induced Mac-1 expression. Med Hypotheses 2003;61:577–9. [6] Jauliac S, Lopez-Rodriguez C, Shaw LM, Brown LF, Rao A, Toker A. The role of NFAT transcription factors in integrinmediated carcinoma invasion. Nat Cell Biol 2002;4:540–544.
Subburaj Kannan DNA Repair and Drug Resistance Group Departments of Microbiology and Immunology School of Medicine University of Texas Medical Branch Galveston, TX 77555, US Tel.: +1 409 750 9060 E-mail address: [email protected] [email protected]
doi:10.1016/j.mehy.2005.01.001
Nanotechnology helps medicine: Nanoscale swimmers and their future applications Delivering materials towards their targets and performing very accurate manipulations using a safe and rapid method inside the human body has been challenging for years. The idea of using very small devices capable of moving within the biological fluids seemed promising, even before the word ‘‘nanotechnology’’ ever existed. To get moving, small living organisms use flagellum or whip-like drive. Unfortunately, molecular engineering of such devices are intricate. Recently, a simple nano-swimmer model is introduced [1], which proposes a sphere-end-rod device that swims like an earthworm by contracting and expanding in one dimension, and should be easy to manufacture as technical difficulties of such nanoscale construc-
tions are declining. It is not unreal to imagine such tools as the first generation of produced nano-swimmers. Combination of nano-computers with these devices can also be an important milestone: Nano-computers would be able to monitor the body conditions [2], and in case of any deficiencies nanoswimmers would be sent as messengers of the computers with the ability of functioning at the ailing site. One possible application of these swimmers might be in delivering drugs inside the body. For example, these swimmers may deliver cancerfighting agents directly to tumors. This might decrease the drug side-effects significantly, as the
Correspondence drugs will have a minimal interaction with other parts of body. It can be even possible to eliminate the tumor cells mechanically. These swimmers might be useful in transferring genes to target tissues at very high efficiencies if they carry encapsulated DNA segments. They might go through the target cell membranes with their forward–backward movement, and deliver the genes directly to the nucleus. This swimmer is perhaps a solution to some old problems in biology and medicine. Future therapeutic approaches are probably fascinating, less destructive and more efficient.
References [1] Najafi A, Golestanian R. Simple swimmer at low Reynolds number: three linked spheres. Phys Rev E 2004;69:062901.
199 [2] Yabrov A, Okunev Y. Medicine without drugs – a new direction for application of nanotechnology. Med Hypotheses 2004;63:149–154.
Zahra Ghalanbor Sayed-Amir Marashi Department of Biotechnology Faculty of Science University of Tehran Tehran, Iran Bijan Ranjbar Department of Bioscience Faculty of Science Tarbiat Modarres University Jalal-Al-Ahmad Highway Tehran Iran Tel.: +98 21 8009730 E-mail address: [email protected]
doi:10.1016/j.mehy.2005.01.023
Making cell-permeable recombinant telomerase (trans-telomerase) through fusion of its catalytic subunit (hTERT) with protein transduction domains (PTD): A possible strategy to overcome replicative senescence during ex vivo culture of primary explanted cells The ex vivo culture of explanted primary cells has numerous applications. In the therapeutic setting, this is most commonly utilized for: (1) extensive proliferation to achieve adequate cell numbers for transplantation i.e., in the case of relatively scarce adult stem cells; (2) exposure to various regimens of cytokines, growth factors or extracellular matrix substratum to modulate cellular function i.e., in tissue engineering; (3) genetic modification before placing it back to the same patient i.e., gene therapy. The nontherapeutic applications would include: (1) clinical diagnostic tests such as amniocentesis and chorionic villus biopsy (CVB); (2) in vitro toxicology testing; (3) basic scientific research in the life sciences.
However, a major bottleneck is the limited life span of primary explanted cells under in vitro culture conditions. Although there is a great deal of variability in this regard, depending on the particular cell lineage concerned, most would display some degree of senescence, after not more than fifty cycles of cell division within in vitro culture. One solution may be to immortalize the cells through chemical treatment, X-ray irradiation or recombinant DNA encoded oncogenes. However, this would obviously limit their therapeutic applications, due to the malignant nature of immortalized cells. Even with non-therapeutic applications such as in vitro toxicology testing and basic scientific research, there is a limited scope for the application of immortalized cells.
Correspondence
References [1] Clair T, Lee HY, Liotta LA, Stracke ML. Autotaxin is an exoenzyme possessing 50 -nucleotide phosphodiesterase/ATP pyrophosphatase and ATPase activities. J Biol Chem 1997;272:996–1001. [2] Tokumura A, Majima E, Kariya Y, Tominaga K, Kogure K, Yasuda K et al. Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase. J Biol Chem 2002;277:39436–42. [3] Mills GB, Moolenaar WH. The emerging role of lysophosphatidic acid in cancer. Nat Rev Cancer 2003;8:582–91. [4] Goding JW, Grobben B, Slegers H. Physiological and pathophysiological functions of the ecto-nucleotide pyrophosphatase/phosphodiesterase family. Biochim Biophys Acta 2003;1638:1–19. [5] Kannan S. Neutrophil chemotaxis: potential role of chemokine receptors in extracellular nucleotide induced Mac-1 expression. Med Hypotheses 2003;61:577–9. [6] Jauliac S, Lopez-Rodriguez C, Shaw LM, Brown LF, Rao A, Toker A. The role of NFAT transcription factors in integrinmediated carcinoma invasion. Nat Cell Biol 2002;4:540–544.
Subburaj Kannan DNA Repair and Drug Resistance Group Departments of Microbiology and Immunology School of Medicine University of Texas Medical Branch Galveston, TX 77555, US Tel.: +1 409 750 9060 E-mail address: [email protected] [email protected]
doi:10.1016/j.mehy.2005.01.001
Nanotechnology helps medicine: Nanoscale swimmers and their future applications Delivering materials towards their targets and performing very accurate manipulations using a safe and rapid method inside the human body has been challenging for years. The idea of using very small devices capable of moving within the biological fluids seemed promising, even before the word ‘‘nanotechnology’’ ever existed. To get moving, small living organisms use flagellum or whip-like drive. Unfortunately, molecular engineering of such devices are intricate. Recently, a simple nano-swimmer model is introduced [1], which proposes a sphere-end-rod device that swims like an earthworm by contracting and expanding in one dimension, and should be easy to manufacture as technical difficulties of such nanoscale construc-
tions are declining. It is not unreal to imagine such tools as the first generation of produced nano-swimmers. Combination of nano-computers with these devices can also be an important milestone: Nano-computers would be able to monitor the body conditions [2], and in case of any deficiencies nanoswimmers would be sent as messengers of the computers with the ability of functioning at the ailing site. One possible application of these swimmers might be in delivering drugs inside the body. For example, these swimmers may deliver cancerfighting agents directly to tumors. This might decrease the drug side-effects significantly, as the
Correspondence drugs will have a minimal interaction with other parts of body. It can be even possible to eliminate the tumor cells mechanically. These swimmers might be useful in transferring genes to target tissues at very high efficiencies if they carry encapsulated DNA segments. They might go through the target cell membranes with their forward–backward movement, and deliver the genes directly to the nucleus. This swimmer is perhaps a solution to some old problems in biology and medicine. Future therapeutic approaches are probably fascinating, less destructive and more efficient.
References [1] Najafi A, Golestanian R. Simple swimmer at low Reynolds number: three linked spheres. Phys Rev E 2004;69:062901.
199 [2] Yabrov A, Okunev Y. Medicine without drugs – a new direction for application of nanotechnology. Med Hypotheses 2004;63:149–154.
Zahra Ghalanbor Sayed-Amir Marashi Department of Biotechnology Faculty of Science University of Tehran Tehran, Iran Bijan Ranjbar Department of Bioscience Faculty of Science Tarbiat Modarres University Jalal-Al-Ahmad Highway Tehran Iran Tel.: +98 21 8009730 E-mail address: [email protected]
doi:10.1016/j.mehy.2005.01.023
Making cell-permeable recombinant telomerase (trans-telomerase) through fusion of its catalytic subunit (hTERT) with protein transduction domains (PTD): A possible strategy to overcome replicative senescence during ex vivo culture of primary explanted cells The ex vivo culture of explanted primary cells has numerous applications. In the therapeutic setting, this is most commonly utilized for: (1) extensive proliferation to achieve adequate cell numbers for transplantation i.e., in the case of relatively scarce adult stem cells; (2) exposure to various regimens of cytokines, growth factors or extracellular matrix substratum to modulate cellular function i.e., in tissue engineering; (3) genetic modification before placing it back to the same patient i.e., gene therapy. The nontherapeutic applications would include: (1) clinical diagnostic tests such as amniocentesis and chorionic villus biopsy (CVB); (2) in vitro toxicology testing; (3) basic scientific research in the life sciences.
However, a major bottleneck is the limited life span of primary explanted cells under in vitro culture conditions. Although there is a great deal of variability in this regard, depending on the particular cell lineage concerned, most would display some degree of senescence, after not more than fifty cycles of cell division within in vitro culture. One solution may be to immortalize the cells through chemical treatment, X-ray irradiation or recombinant DNA encoded oncogenes. However, this would obviously limit their therapeutic applications, due to the malignant nature of immortalized cells. Even with non-therapeutic applications such as in vitro toxicology testing and basic scientific research, there is a limited scope for the application of immortalized cells.