Theranostics is a concept of integrating imaging and therapy into a single platform for use in the next generation of personalized medicine to meet the challenges in modern health care.(1) The diagnostic role of theranostic agents reports the presence of a disease, its status, and its response to a specific treatment, while the therapeutic role of the agent can be implemented in several forms:(2)(i) The first is imaging-guided surgery for tumor resection and postsurgery evaluation. Intraoperative visualization of diseased areas is important for precision surgery, as the location of the tumor may change after presurgical imaging and during resection.(3-6) Furthermore, postsurgical assessment is valuable in ensuring complete removal of the diseased sections.(ii) The second is delivery or release of therapeutic entities to the intended site. The delivered entities can be small molecule chemotherapeutics (such as cisplatin, doxorubicin, and paclitaxel), biologics (such as protein drugs and antibodies), gene products (DNA, siRNA, and miRNA), nanotherapeutic agents, and even cells.(7-9) The release/therapy can be light-activated such as in photodynamic therapy (PDT) for destruction of the tumor or heat activated by nonradiative conversion of absorbed photon energy into heat such as in photothermal therapy (PTT),(10) which disrupts the structure of the cells and shrinks the tumor volume.(11)(iii) The third is disruption of a cellular or metabolic pathway.(2) An occupation of specific cell surface receptors by introduced theranostic agents with appropriate chemistry can disrupt cell regulation, producing a therapeutic effect.(12) Theranostics offers an opportunity to embrace multiple techniques to arrive at a comprehensive imaging/therapy regimen. Incorporation of therapeutic functions into molecular imaging contrasts plays a pivotal role in developing theranostic agents.(13) Molecular imaging using photoluminescence (PL) spectroscopy is an important technique in biochemistry and molecular biology. It has become the dominant method revolutionizing medical diagnostics, bioassays, DNA sequencing, and genomics.(14-17) It can be used to study a wide range of biological specimens, from cells to ex vivo tissue samples, and to in vivo imaging of live objects; it can also cover a broad range of length scale, from submicrometer-sized viruses and bacteria, to macroscopic-sized live biological species.(17-19) Thus, PL imaging provides a powerful noninvasive tool to visualize morphological details in tissue with subcellular resolution. However, the imperfect optical properties of conventional PL imaging agents and the challenge in incorporation of therapeutic functions onto them have severely limited their abilities for use in theranostics.

PL imaging generally employs exogenous contrast agents, which encompass organic dyes,(20, 21) organically modified silica,(22-24) fluorescent proteins,(25-28) metal complexes,(11, 29-31) and semiconductor quantum dots (QDs).(32-35) Most of these conventional contrast agents utilize Stokes-shifted emission using excitation in the ultraviolet (UV) or blue-green visible spectral ranges. These conventional PL imaging agents when excited in such spectral range have a number of limitations:(i) low signal-to-background ratio (SBR) caused by unwanted autofluorescence as well as by strong light scattering from the biological tissues (such as fur, skin, and tissues) when excited at short wavelengths;(ii) low penetration depth of UV and visible excitation and/or emission light in biological tissues; and (iii) potential DNA damage and cell death due to long-term exposure to short wavelength, particularly UV excitation. In addition, there is also a …