title: The role of cell cycle in the efficiency and activity of cancer nanomedicines.
abstract: BACKGROUND
  With a wealth of knowledge on the effect of nanoparticle properties, including size, shape, charge and composition, on intracellular delivery, little has been reported on the effect of the cell cycle on the intracellular delivery and activity of nanomedicines including non-viral gene delivery systems. The aim of this review is to shed a light on this topic.
  
  
  METHODS
  It is now evident that nanoparticle cell uptake varies with the cell cycle phase. This review addresses this variation by dissecting the effect of cell population heterogeneity on the intracellular delivery and activity of nanomedicines with a special focus on non-viral gene delivery and combination therapy modalities that utilize cell cycle inhibitors as co-targets for therapy. In addition, the importance of three-dimensional (3D) culture systems in the drug delivery field within the context of the cell cycle will be addressed.
  
  
  CONCLUSIONS
  The understanding of the cell cycle machinery has improved dramatically over the last few decades. Developing combination therapy modalities that target the cell cycle to achieve better cancer patient outcome should now be the focus. Furthermore, more effort should be placed on developing a reliable, consistent, high throughput 3D cell culture system since these systems more closely resemble the cell cycle status of in vivo tumors. A switch from 2D to 3D culture systems, to more accurately predict the in vivo efficacy of nanoparticle drug delivery systems, is desirable.
authors: Northeastern University, Center for Pharmaceutical Biotechnology and Nanomedicine, Department of Pharmaceutical Sciences, 140 The Fenway, Room 236, 360 Huntington Ave, Boston, MA 02115, USA.
authors: Abraham H
authors: AH
authors: Abouzeid
authors: Vladimir P
authors: VP
authors: Torchilin
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division; D003131:Combined Modality Therapy; D016503:Drug Delivery Systems; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D050997:Nanomedicine; D053758:Nanoparticles; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology