Editorial
Special Issue: Next Generation Therapeutics
Next-generation therapeutics Ernesto Andrianantoandro (Editor) Trends in Biotechnology
Conventional therapies followed in the footsteps of an analytical and reductive approach to basic biology, and have relied on chemical specificity for their effectiveness. Many of this generation’s best therapeutics exert control in the simplest way; they inhibit a biological process through a single molecular target. This straightforward approach to exerting control over a disease state has met with success in many cases. However, in the coming years, complex disease states, such as cancer and degenerative disorders, will call for complex therapeutic solutions. Traumatic injury and tissue damage also elude straightforward solutions. The advent of regenerative medicine, progress in materials science, and the promise of nanotechnology are coming together to usher in a new generation of therapeutics. This special issue of Trends in Biotechnology begins with a Letter by Jerome Guicheux and colleagues about a topic at the frontier of tissue engineering. They explore strategies for the regeneration of the intraverterbral disc (IVD), and these include both cell-based and biomaterialsbased approaches. However, extant challenges include: understanding how mature nucleus pulposus cells develop from their stem cell precursors, developing appropriate biomimetic scaffolds, and determining a suitable animal model for IVD degeneration. Next, regenerative medicine is put into perspective economically and socially by Anna French and colleagues in a Science & Society article on co-development partnerships in regenerative medicine. They focus on partnerships between pharmaceutical companies, academia, and small and medium-sized enterprises in the development of cellbased therapies. Two Opinion articles explore cutting edge advances in biomaterials and nanoparticle-based therapies. Werner Mu¨ller and colleagues discuss the possibility of applying biomineralization to regenerative medicine. In contrast to artificially derived biomimetic materials, biosilica and biocalcite can be formed by enzymes. These naturally occurring biominerals have the potential to be well-suited scaffolds for bone regeneration. Sangeeta Bhatia and Sabine Hauert discuss a unique strategy for applying nanoparticle-based therapeutics to fighting cancer. They advocate designing nanoparticles to behave cooperatively, leveraging features of ‘swarm intelligence’ to maximize therapeutic effects. Self-assembly or Corresponding author: Andrianantoandro, E. ([email protected]). 0167-7799/ ß 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tibtech.2014.07.001
disassembly of nanoparticle structures can aid in delivering therapeutic cargo. Conversely, nanoparticles designed to deposit and pick up cues in their environment can, analogous to ants finding their way to food, organize to home in on tumors. Engineering collective behavior into therapeutic agents represents a new and promising paradigm for cancer therapy. Similarly, Carl Figdor and colleagues review advances in fighting cancer via stimulating the immune system. This approach takes advantage of a more direct biomimetic strategy: engineering artificial antigen-presenting ‘cells’. In efforts to circumvent the difficulties of autologous cellbased therapies, researchers have used microparticles and nanoparticles as scaffolds for presenting T cell stimulating molecules and tumor-specific antigens. Redirecting T cells to home in on tumors in this therapeutic strategy in effect reengineers the body’s own defense mechanisms. In a Review that brings together a diversity of approaches, Peter Ghoroghchian and Zhimin Tao survey mircoparticle, nanoparticle, and stem cell-based blood substitutes. Despite the widespread need for artificial red blood cell (RBC) substitutes, previous attempts with hemoglobin-based oxygen carriers were not as successful as hoped. Microparticle and nanoparticle oxygen carriers display improved biocompatibility through modifications of their surface or by carrying additional payloads that ameliorate toxicity. Although these particles are suitable for short-term oxygenation of tissues, combating chronic hypoxia requires a longer-lived oxygen carrier; for example, in the form of RBC-like cells derived from stem cells. Bringing together another diverse set of approaches, Dimitrios Zeugolis and colleagues focus on tendon repair and review research efforts to maintain the tenogenic phenotype and also to differentiate stem cells towards a tenogenic lineage. The in vivo tenogenic niche provides physical, chemical, and biological cues for developing cells. Micro- and nanofabrication of biomaterial substrates, control of oxygen tension, and supplementation with the appropriate growth factors can hold the key to recapitulating the tenogenic niche in vitro. To close out the issue, let us explore further the notion of using cues to control cell fate and turn to a Review by Kristin Andreas and colleagues. They review the frontier of in situ tissue engineering, which takes advantage of stem cell homing. The new cancer therapeutic approaches discussed earlier utilize homing of nanoparticles or immune cells to tumors, targeting them for destruction. By contrast, the in situ tissue engineering approach recruits stem cells to injury sites to promote repair and healing. Advances in biomaterials have propelled the development of devices Trends in Biotechnology, September 2014, Vol. 32, No. 9
431
Editorial used for delivering the appropriate cue, in this case a chemokine, to the damaged site. Looking across the issue, our authors have brought to the forefront several themes that could impact the future of therapeutics. There seems to be a transition from a single-target approach to approaches that account for a multiplicity of factors or targets. In effect, many of these new therapeutic strategies target systems instead of just molecules. The path to a desired effect could be indirect. Achieving such effects would rely on diverting, co-opting,
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Trends in Biotechnology September 2014, Vol. 32, No. 9
or hijacking natural processes as the means. This is not to say that analysis, specificity, or control would be abandoned, but the locus of this mindset could move. Perhaps the most fulfilling efforts will come from mastering the mechanical and physical properties of biomaterials or nanoparticles, or from controlling cell fate and movement. I hope you all enjoy reading this special issue, and I welcome your comments and ideas; feel free to contact us with any feedback or questions at [email protected].
Special Issue: Next Generation Therapeutics
Next-generation therapeutics Ernesto Andrianantoandro (Editor) Trends in Biotechnology
Conventional therapies followed in the footsteps of an analytical and reductive approach to basic biology, and have relied on chemical specificity for their effectiveness. Many of this generation’s best therapeutics exert control in the simplest way; they inhibit a biological process through a single molecular target. This straightforward approach to exerting control over a disease state has met with success in many cases. However, in the coming years, complex disease states, such as cancer and degenerative disorders, will call for complex therapeutic solutions. Traumatic injury and tissue damage also elude straightforward solutions. The advent of regenerative medicine, progress in materials science, and the promise of nanotechnology are coming together to usher in a new generation of therapeutics. This special issue of Trends in Biotechnology begins with a Letter by Jerome Guicheux and colleagues about a topic at the frontier of tissue engineering. They explore strategies for the regeneration of the intraverterbral disc (IVD), and these include both cell-based and biomaterialsbased approaches. However, extant challenges include: understanding how mature nucleus pulposus cells develop from their stem cell precursors, developing appropriate biomimetic scaffolds, and determining a suitable animal model for IVD degeneration. Next, regenerative medicine is put into perspective economically and socially by Anna French and colleagues in a Science & Society article on co-development partnerships in regenerative medicine. They focus on partnerships between pharmaceutical companies, academia, and small and medium-sized enterprises in the development of cellbased therapies. Two Opinion articles explore cutting edge advances in biomaterials and nanoparticle-based therapies. Werner Mu¨ller and colleagues discuss the possibility of applying biomineralization to regenerative medicine. In contrast to artificially derived biomimetic materials, biosilica and biocalcite can be formed by enzymes. These naturally occurring biominerals have the potential to be well-suited scaffolds for bone regeneration. Sangeeta Bhatia and Sabine Hauert discuss a unique strategy for applying nanoparticle-based therapeutics to fighting cancer. They advocate designing nanoparticles to behave cooperatively, leveraging features of ‘swarm intelligence’ to maximize therapeutic effects. Self-assembly or Corresponding author: Andrianantoandro, E. ([email protected]). 0167-7799/ ß 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tibtech.2014.07.001
disassembly of nanoparticle structures can aid in delivering therapeutic cargo. Conversely, nanoparticles designed to deposit and pick up cues in their environment can, analogous to ants finding their way to food, organize to home in on tumors. Engineering collective behavior into therapeutic agents represents a new and promising paradigm for cancer therapy. Similarly, Carl Figdor and colleagues review advances in fighting cancer via stimulating the immune system. This approach takes advantage of a more direct biomimetic strategy: engineering artificial antigen-presenting ‘cells’. In efforts to circumvent the difficulties of autologous cellbased therapies, researchers have used microparticles and nanoparticles as scaffolds for presenting T cell stimulating molecules and tumor-specific antigens. Redirecting T cells to home in on tumors in this therapeutic strategy in effect reengineers the body’s own defense mechanisms. In a Review that brings together a diversity of approaches, Peter Ghoroghchian and Zhimin Tao survey mircoparticle, nanoparticle, and stem cell-based blood substitutes. Despite the widespread need for artificial red blood cell (RBC) substitutes, previous attempts with hemoglobin-based oxygen carriers were not as successful as hoped. Microparticle and nanoparticle oxygen carriers display improved biocompatibility through modifications of their surface or by carrying additional payloads that ameliorate toxicity. Although these particles are suitable for short-term oxygenation of tissues, combating chronic hypoxia requires a longer-lived oxygen carrier; for example, in the form of RBC-like cells derived from stem cells. Bringing together another diverse set of approaches, Dimitrios Zeugolis and colleagues focus on tendon repair and review research efforts to maintain the tenogenic phenotype and also to differentiate stem cells towards a tenogenic lineage. The in vivo tenogenic niche provides physical, chemical, and biological cues for developing cells. Micro- and nanofabrication of biomaterial substrates, control of oxygen tension, and supplementation with the appropriate growth factors can hold the key to recapitulating the tenogenic niche in vitro. To close out the issue, let us explore further the notion of using cues to control cell fate and turn to a Review by Kristin Andreas and colleagues. They review the frontier of in situ tissue engineering, which takes advantage of stem cell homing. The new cancer therapeutic approaches discussed earlier utilize homing of nanoparticles or immune cells to tumors, targeting them for destruction. By contrast, the in situ tissue engineering approach recruits stem cells to injury sites to promote repair and healing. Advances in biomaterials have propelled the development of devices Trends in Biotechnology, September 2014, Vol. 32, No. 9
431
Editorial used for delivering the appropriate cue, in this case a chemokine, to the damaged site. Looking across the issue, our authors have brought to the forefront several themes that could impact the future of therapeutics. There seems to be a transition from a single-target approach to approaches that account for a multiplicity of factors or targets. In effect, many of these new therapeutic strategies target systems instead of just molecules. The path to a desired effect could be indirect. Achieving such effects would rely on diverting, co-opting,
432
Trends in Biotechnology September 2014, Vol. 32, No. 9
or hijacking natural processes as the means. This is not to say that analysis, specificity, or control would be abandoned, but the locus of this mindset could move. Perhaps the most fulfilling efforts will come from mastering the mechanical and physical properties of biomaterials or nanoparticles, or from controlling cell fate and movement. I hope you all enjoy reading this special issue, and I welcome your comments and ideas; feel free to contact us with any feedback or questions at [email protected].
