Upconversion nanocrystals (UCNs) display near-infrared (NIR)-responsive photoluminescent properties for NIR imaging and drug delivery. The development of effective strategies for UCN integration with other complementary nanostructures for targeting and drug conjugation is highly desirable. This study reports on a core/shell-based theranostic system designed by UCN integration with a folate (FA)-conjugated dendrimer for tumor targeting and with photocaged doxorubicin as a cytotoxic agent. Two types of UCNs (NaYF4:Yb/Er (or Yb/Tm); diameter = ≈50 to 54 nm) are described, each displaying distinct emission properties upon NIR (980 nm) excitation. The UCNs are surface modified through covalent attachment of photocaged doxorubicin (ONB-Dox) and a multivalent FA-conjugated polyamidoamine (PAMAM) dendrimer G5(FA)6 to prepare UCN@(ONB-Dox)(G5FA). Surface plasmon resonance experiments performed with G5(FA)6 dendrimer alone show nanomolar binding avidity (KD = 5.9 × 10(-9) M) to the folate binding protein. This dendrimer binding corresponds with selective binding and uptake of UCN@(ONB-Dox)(G5FA) by FAR-positive KB carcinoma cells in vitro. Furthermore, UCN@(ONB-Dox)(G5FA) treatment of FAR(+) KB cells inhibits cell growth in a light dependent manner. These results validate the utility of modularly integrated UCN-dendrimer nanocomposites for cell type specific NIR imaging and light-controlled drug release, thus serving as a new theranostic system.

The use of coumarin caged molecules has been well documented in numerous photocaging applications including for the spatiotemporal control of Cre-estrogen receptor (Cre-ERT2) recombinase activity. In this article, we report that 4-hydroxytamoxifen (4OHT) caged with coumarin via a conventional ether linkage led to an unexpected photo-Claisen rearrangement which significantly competed with the release of free 4OHT. The basis for this unwanted reaction appears to be related to the coumarin structure and its radical-based mechanism of uncaging, as it did not occur in ortho-nitrobenzyl (ONB) caged 4OHT that was otherwise linked in the same manner. In an effort to perform design optimization, we introduced a self-immolative linker longer than the ether linkage and identified an optimal linker which allowed rapid 4OHT release by both single-photon and two-photon absorption mechanisms. The ability of this construct to actively control Cre-ERT2 mediated gene modifications was investigated in mouse embryonic fibroblasts (MEFs) in which the expression of a green fluorescent protein (GFP) reporter dependent gene recombination was controlled by 4OHT release and measured by confocal fluorescence microscopy and flow cytometry. In summary, we report the implications of this photo-Claisen rearrangement in coumarin caged compounds and demonstrate a rational linker strategy for addressing this unwanted side reaction.

Single-crystalline gallium phosphide (GaP) surfaces have been functionalized with alkyl groups via a sequential Cl-activation, Grignard reaction process. X-ray photoelectron (XP) spectra of freshly etched GaP(111)A surfaces demonstrated reproducible signals for surficial Cl after treatment with PCl(5) in chlorobenzene. The measured Cl content consistently corresponded to approximately a monolayer of coverage on GaP(111)A. In contrast, GaP(111)B surfaces treated with the same PCl(5) solution under the same conditions exhibited macroscale roughening and yielded XP spectra that showed irreproducible Cl surface content often below the limit of detection of the spectrometer. The Cl-activated GaP(111)A surfaces were reactive toward alkyl Grignard reagents. Sessile contact angle measurements between water and GaP(111)A after various levels of treatment showed that GaP(111)A surfaces became significantly more hydrophobic following reaction with either CH(3)MgCl or C(18)H(37)MgCl. GaP(111)A surfaces reacted with C(18)H(37)MgCl demonstrated wetting properties consistent with surfaces modified with a dense layer of long alkyl chains. High-resolution C 1s XP spectra indicated that the carbonaceous species at GaP(111)A surfaces treated with Grignard reagents could not be ascribed solely to adventitious carbon. A shoulder in the C 1s XP spectra occurred at slightly lower binding energies for these samples, commensurate with the formation of Ga-C bonds. High-resolution P 2p XP spectra taken at various times during prolonged direct exposure to ambient laboratory air indicated that the resistance of GaP(111)A to surface oxidation was greatly enhanced after surface modification with alkyl groups. GaP(111)A samples that had been functionalized with C(18)H(37)- groups exhibited less than 0.1 nm of surface oxide after 7 weeks of continuous exposure to ambient air. GaP(111)A surfaces terminated with C(18)H(37)- groups were also used as platforms in Schottky heterojunctions with Hg. In comparison to freshly etched GaP(111)A, the alkyl-terminated GaP(111)A samples yielded current-voltage responses that were in accord with metal-insulator-semiconductor devices and indicated that this reaction strategy could be used to alter rates of heterogeneous charge transfer controllably. The wet chemical surface functionalization strategy described herein does not involve thiol/sulfide chemistry or gas-phase pretreatments and represents a new synthetic methodology for controlling the interfacial properties of GaP and related Ga-based III-V semiconductors.

We report an active delivery mechanism targeted specifically to Gram(−) bacteria based on the photochemical release of photocaged ciprofloxacin carried by a cell wall-targeted dendrimer nanoconjugate.