Photocontrolled nanoparticle delivery systems for biomedical applications.

"Smart" stimuli-responsive nanomaterials are becoming popular as targeted delivery systems because they allow the use of internal or external stimuli to achieve spatial or temporal control over the delivery process. Among the stimuli that have been used, light is of special interest because it is not only noninvasive but also controllable both spatially and temporally, thus allowing unprecedented control over the delivery of bioactive molecules such as nucleic acids, proteins, drugs, etc. This is particularly advantageous for biomedical applications where specificity and selectivity are highly desired. Several strategies have evolved under the umbrella of light based delivery systems and can be classified into three main groups. The first strategy involves "caging" of the bioactive molecule using photolabile groups, loading these caged molecules onto a carrier and then "uncaging" or activating them at the targeted site upon irradiation with light of a particular wavelength. The second strategy makes use of nanocarriers that themselves are made photoresponsive either through modification with photosensitive groups or through the attachment of photolinkers on the carrier surface. These nanoparticles upon irradiation dissociate, releasing the cargo encapsulated within, or the photolinkers attaching the cargo to the surface get cleaved, resulting in release. The third approach makes use of the surface plasmon resonance of noble metal based nanoparticles. Upon irradiation with light at the plasmon resonant frequency, the resulting thermal or nonthermal field enhancement effects facilitate the release of bioactive molecules loaded onto the nanoparticles. In addition, other materials, certain metal sulfides, graphene oxide, etc., also exhibit photothermal transduction that can be exploited for targeted delivery. These approaches, though effective, are constrained by their predominant use of UV or visible light to which most photolabile groups are sensitive. Near infrared (NIR) excitation is preferred because NIR light is safer and can penetrate deeper in biological tissues. However, most photolabile groups cannot be excited by NIR light directly. So light conversion from NIR to UV/visible is required. Nanomaterials that display upconversion or two-photon-excitation properties have been developed that can serve as nanotransducers, converting NIR to UV/visible light to which the aforementioned photoresponsive moieties are sensitive. This Account will review the existing light-based nanoparticle delivery systems, their applications, the limitations they face, and the technologies that have emerged in an effort to overcome these limitations.