Design considerations for nanotherapeutics in oncology.
Nanotherapeutics have improved the quality of life of cancer patients, primarily by reducing the adverse effects of chemotherapeutic agents, but improvements in overall survival are modest. This is in large part due to the fact that the enhanced permeability and retention effect, which is the basis for the use of nanoparticles in cancer, can be also a barrier to the delivery of nanomedicines. A careful design of nanoparticle formulations can overcome barriers posed by the tumor microenvironment and result in better treatments. In this review, we first discuss strengths and limitations of clinically-approved nanoparticles. Then, we evaluate design parameters that can be modulated to optimize delivery. The benefits of active tumor targeting and drug release rate on intratumoral delivery and treatment efficacy are also discussed. Finally, we suggest specific design strategies that should optimize delivery to most solid tumors and discuss under what conditions active targeting would be beneficial.


BACKGROUND
Advances in nanotechnology have seen the introduction of new treatment modalities for cancer. The principle of action using nanocarriers for drug delivery is based mostly on the Enhanced Permeability and Retention effect. This phenomenon however, can also be a hindrance. In this article, the authors performed an in-depth review on various nanoparticle platforms in cancer therapeutics. They also suggested options to improve drug delivery, in terms of carrier design.
Cancer Biophysics Laboratory, Department of Mechanical and Manufacturing Engineering, University of Cyprus, Nicosia, Cyprus. Electronic address: tstylian@ucy.ac.cy.
Triantafyllos
T
Stylianopoulos
Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: jain@steele.mgh.harvard.edu.
Rakesh K
RK
Jain
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D050997:Nanomedicine / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism; D036103:Nanotechnology / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy*; D011788:Quality of Life
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations
Cancer therapy; Controlled drug release; EPR effect; Nanomedicine; Nanoparticle targeting