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Selective Cell Targeting with Light-Absorbing Microparticles and Nanoparticles

Costas M. Pitsillides ^* , Edwin K. Joe ^*, Xunbin Wei ^*, R. Rox Anderson ^* and Charles P. Lin ^*

^* Wellman Laboratories of Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114 USA; and Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02137 USA

Correspondence: Address reprint requests to Charles P. Lin, Wellman Laboratories of Photomedicine, Massachusetts General Hospital/Harvard Medical School, BHX 630, 40 Blossom St., Boston, MA 02114. Tel.: 001-617-724-3957; Fax: 001-617-724-2075; E-mail: lin@helix.mgh.harvard.edu.

We describe a new method for selective cell targeting based on the use of light-absorbing microparticles and nanoparticles that are heated by short laser pulses to create highly localized cell damage. The method is closely related to chromophore-assisted laser inactivation and photodynamic therapy, but is driven solely by light absorption, without the need for photochemical intermediates (particularly singlet oxygen). The mechanism of light-particle interaction was investigated by nanosecond time-resolved microscopy and by thermal modeling. The extent of light-induced damage was investigated by cell lethality, by cell membrane permeability, and by protein inactivation. Strong particle size dependence was found for these interactions. A technique based on light to target endogenous particles is already being exploited to treat pigmented cells in dermatology and ophthalmology. With exogenous particles, phamacokinetics and biodistribution studies are needed before the method can be evaluated against photodynamic therapy for cancer treatment. However, particles are unique, unlike photosensitizers, in that they can remain stable and inert in cells for extended periods. Thus they may be particularly useful for prelabeling cells in engineered tissue before implantation. Subsequent irradiation with laser pulses will allow control of the implanted cells (inactivation or modulation) in a noninvasive manner.

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