title: Extracellularly activatable nanocarriers for drug delivery to tumors.
abstract: BACKGROUND
  Nanoparticles (NPs) for drug delivery to tumors need to satisfy two seemingly conflicting requirements: they should maintain physical and chemical stability during circulation and be able to interact with target cells and release the drug at desired locations with no substantial delay. The unique microenvironment of tumors and externally applied stimuli provide a useful means to maintain a balance between the two requirements.
  
  
  METHODS
  We discuss nanoparticulate drug carriers that maintain stable structures in normal conditions but respond to stimuli for the spatiotemporal control of drug delivery. We first define the desired effects of extracellular activation of NPs and frequently used stimuli and then review the examples of extracellularly activated NPs.
  
  
  CONCLUSIONS
  Several challenges remain in developing extracellularly activatable NPs. First, some of the stimuli-responsive NPs undergo incremental changes in response to stimuli, losing circulation stability. Second, the applicability of stimuli in clinical settings is limited due to the occasional occurrence of the activating conditions in normal tissues. Third, the construction of stimuli-responsive NPs involves increasing complexity in NP structure and production methods. Future efforts are needed to identify new targeting conditions and increase the contrast between activated and nonactivated NPs while keeping the production methods simple and scalable.
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA.
authors.forename: Sara A
authors.initials: SA
authors.lastname: Abouelmagd
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA.
authors.forename: Hyesun
authors.initials: H
authors.lastname: Hyun
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA.|Weldon School of Biomedical Engineering, Purdue University, 206 South Martin Jischke Drive, West Lafayette, IN 47907, USA.
authors.forename: Yoon
authors.initials: Y
authors.lastname: Yeo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers
keywords: drug delivery; extracellular activation; nanocarriers; nanoparticles; stimuli-responsive; tumor microenvironment