A new approach for photoluminescence imaging in vitro and in vivo has been shown, utilizing near infrared to near infrared (NIR-to-NIR) up-conversion in nanophosphors. This NIR-to-NIR up-conversion process provides deeper light penetration into biological specimen and results in high contrast optical imaging due to absence of an autofluorescence background and decreased light scattering. Aqueous dispersible fluoride (NaYF4) nanocrystals (20–30 nm size) co-doped with the rare earth ions, Tm3+ and Yb3+, were synthesized and characterized by TEM, XRD and photoluminescence (PL) spectroscopy. In vitro cellular uptake was shown by the PL microscopy visualizing the characteristic emission of Tm3+ at ~ 800 nm excited with 975 nm. No apparent cytotoxicity was observed. Subsequent animal imaging studies were performed using Balb-c mice injected intravenously with up-converting nanophosphors, demonstrating the high contrast PL imaging in vivo.

A novel nanoparticle-based drug carrier for photodynamic therapy is reported which can provide stable aqueous dispersion of hydrophobic photosensitizers, yet preserve the key step of photogeneration of singlet oxygen, necessary for photodynamic action. A multidisciplinary approach is utilized which involves (i) nanochemistry in micellar cavity to produce these carriers, (ii) spectroscopy to confirm singlet oxygen production, and (iii) in vitro studies using tumor cells to investigate drug-carrier uptake and destruction of cancer cells by photodynamic action. Ultrafine organically modified silica-based nanoparticles (diameter approximately 30 nm), entrapping water-insoluble photosensitizing anticancer drug 2-devinyl-2-(1-hexyloxyethyl) pyropheophorbide, have been synthesized in the nonpolar core of micelles by hydrolysis of triethoxyvinylsilane. The resulting drug-doped nanoparticles are spherical, highly monodispersed, and stable in aqueous system. The entrapped drug is more fluorescent in aqueous medium than the free drug, permitting use of fluorescence bioimaging studies. Irradiation of the photosensitizing drug entrapped in nanoparticles with light of suitable wavelength results in efficient generation of singlet oxygen, which is made possible by the inherent porosity of the nanoparticles. In vitro studies have demonstrated the active uptake of drug-doped nanoparticles into the cytosol of tumor cells. Significant damage to such impregnated tumor cells was observed upon irradiation with light of wavelength 650 nm. Thus, the potential of using ceramic-based nanoparticles as drug carriers for photodynamic therapy has been demonstrated.

Successful translation of the use of nanoparticles from laboratories to clinics requires exhaustive and elaborate studies involving the biodistribution, clearance and biocompatibility of nanoparticles for in vivo biomedical applications. We report here the use of multimodal organically modified silica (ORMOSIL) nanoparticles for in vivo bioimaging, biodistribution, clearance and toxicity studies. We have synthesized ORMOSIL nanoparticles with diameters of 20-25 nm, conjugated with near infra-red (NIR) fluorophores and radiolabelled them with 124 I, for optical and PET imaging in vivo. The biodistribution of the non targeted nanoparticles was studied in non-tumored nude mice by optical fluorescence imaging, as well by measuring the radioactivity from harvested organs. Biodistribution studies showed a greater accumulation of nanoparticles in liver, spleen and stomach than in kidney, heart and lungs. The clearance studies carried out over a period of 15 days indicated hepatobiliary excretion of the nanoparticles. Selected tissues were analyzed for any potential toxicity by histological analysis, which confirmed the absence of any adverse effect or any other abnormalities in the tissues. The results demonstrate that these multimodal nanoparticles have potentially ideal attributes for use as biocompatible probes for in vivo imaging. KeywordsORMOSIL Nanoparticles; optical and PET Imaging; NIR fluorophore; 124 I radiolabeling; Biodistribution; clearance and toxicity Nanomaterials promise to address the current limitations of sensitivity and specificity of medical diagnostics, as well as significantly improve the outcome of existing and emerging therapeutics, via the introduction of new generation of multimodal nanoprobes. [1][2][3][4][5][6] In this regard, it is critical to design nanoprobes with desired composition, size and surface functionalities, and rigorously test them in vitro and in vivo for their safety and efficiency. Also biocompatibility and biodegradation of the nanoprobe materials play an important role in the use of the nanoprobes in the field of diagnostic and therapeutic applications.The rise in nanoprobes development has bolstered the prospects of in vivo optical imaging through the development of a variety of NIR-luminescent nanoformulations, which include quantum dots, 7 upconverting nanophosphors, 8 Herein, we report the synthesis of ultrafine ORMOSIL nanoparticles (diameter ∼20 nm), conjugated with a near-infra-red (NIR) fluorophore, as optical probes. The resulting NIRnanoparticles will facilitate optical bioimaging in the NIR window, with maximum tissue penetration of light and minimum background signal. 23, 24 Furthermore, we have also conjugated the well-known positron emission tomographic (PET) imaging probe Iodine-124 with the nanoparticle, which will allow bioimaging independent of tissue-depth, as well as more accurate quantification of accumulation of nanoparticles in various major organs in vivo. These multimodal nanoprobes have been injected systemically in mice, and their in v...