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Near-infrared remotely triggered drug-release strategies for cancer treatment

  1. Naomi J. Halasa,b,e,f,1
  1. aDepartment of Chemistry, Rice University, Houston, TX 77005;
  2. bDepartment of Electrical and Computer Engineering, Rice University, Houston, TX 77005;
  3. cThe Niels Bohr Institute, University of Copenhagen, 2100 Copenhagen, Denmark;
  4. dDepartment of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611;
  5. eDepartment of Physics and Astronomy, Rice University, Houston, TX 77005;
  6. fDepartment of Bioengineering, Rice University, Houston, TX 77005
  1. Contributed by Naomi J. Halas, October 6, 2017 (sent for review July 24, 2017; reviewed by Omid C. Farokhzad and Vincent Rotello)

Significance

Gold-based nanoparticles that absorb near-infrared light have shown the potential to selectively target and treat cancer through highly efficient light-to-heat conversion. This study shows that gold-based nanoparticles can be coated with drug-bearing host biomolecules for remotely triggerable release. Near-infrared light-triggered release of docetaxel from a nanoshell-based DNA host complex, and lapatinib from nanoshell-based DNA and human serum albumin host complexes, is demonstrated. There is a strong dependence upon the type of near-infrared illumination––continuous wave or pulsed––specific to the drug-laden host molecules. Localizing drug delivery both spatially and temporally by combining nanoshell-based complexes and pulsed-laser irradiation is a promising strategy for highly controlled drug delivery that can apply to a myriad of therapeutic applications.

Abstract

Remotely controlled, localized drug delivery is highly desirable for potentially minimizing the systemic toxicity induced by the administration of typically hydrophobic chemotherapy drugs by conventional means. Nanoparticle-based drug delivery systems provide a highly promising approach for localized drug delivery, and are an emerging field of interest in cancer treatment. Here, we demonstrate near-IR light-triggered release of two drug molecules from both DNA-based and protein-based hosts that have been conjugated to near-infrared-absorbing Au nanoshells (SiO2 core, Au shell), each forming a light-responsive drug delivery complex. We show that, depending upon the drug molecule, the type of host molecule, and the laser illumination method (continuous wave or pulsed laser), in vitro light-triggered release can be achieved with both types of nanoparticle-based complexes. Two breast cancer drugs, docetaxel and HER2-targeted lapatinib, were delivered to MDA-MB-231 and SKBR3 (overexpressing HER2) breast cancer cells and compared with release in noncancerous RAW 264.7 macrophage cells. Continuous wave laser-induced release of docetaxel from a nanoshell-based DNA host complex showed increased cell death, which also coincided with nonspecific cell death from photothermal heating. Using a femtosecond pulsed laser, lapatinib release from a nanoshell-based human serum albumin protein host complex resulted in increased cancerous cell death while noncancerous control cells were unaffected. Both methods provide spatially and temporally localized drug-release strategies that can facilitate high local concentrations of chemotherapy drugs deliverable at a specific treatment site over a specific time window, with the potential for greatly minimized side effects.

Footnotes

  • ?1To whom correspondence should be addressed. Email: halas{at}rice.edu.
  • Author contributions: A.M.G., O.N., S.E.C., and N.J.H. designed research; A.M.G., O.N., K.N., L.H., and M.-R.C. performed research; A.M.G., O.N., M.-R.C., and S.E.C. analyzed data; and A.M.G., O.N., L.H., M.-R.C., S.E.C., and N.J.H. wrote the paper.

  • Reviewers: O.C.F., Brigham and Women’s Hospital; and V.R., Harvard Medical School.

  • The authors declare no conflict of interest.

  • This article contains supporting information online at www.danielhellerman.com/lookup/suppl/doi:10.1073/pnas.1713137114/-/DCSupplemental.

Published under the PNAS license.

Online Impact

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