Facile synthesis of fluorinated nanophotosensitizers with self-supplied oxygen for efficient photodynamic therapy.

Tumor hypoxia severely reduces the efficiency of photodynamic therapy (PDT) through the insufficient supply of oxygen. In this work, we reported on a design of fluorinated nanophotosensitizers (NPSs) prepared by a facile reprecipitation-encapsulation method, with the aim of addressing the issue of hypoxia. The fluorinated NPSs consisted of a hybrid particle core of perfluorosiloxane-polystyrene, doped with a fluorinated photosensitizer, and a biocompatible poly-l-lysine shell. Compared with non-fluorinated counterpart NPSs that are similarly prepared except for the replacement of perfluorosiloxane with alkoxysilane, the fluorinated NPSs saturated with O2 exhibit approximately 3.5 fold higher singlet oxygen production yield and higher in vitro PDT efficiency due to the O2-carrying capability of intra-particle 'F-C' bonds.

Optically Encoded Semiconducting Polymer Dots with Single-Wavelength Excitation for Barcoding and Tracking of Single Cells.

Multiplexed optical encoding is emerging as a powerful technique for high-throughput cellular analysis and molecular assays. Most of the developed optical barcodes, however, either suffer from large particle size or are incompatible with most commercial optical instruments. Here, a new type of nanoscale fluorescent barcode (Pdot barcodes) was prepared from semiconducting polymers. The Pdot barcodes possess the merits of small size (∼20 nm in diameter), narrow emission bands (full-width-at-half-maximum (fwhm) of 30-40 nm), three-color emissions (blue, green, and red) under single-wavelength excitation, a high brightness, good pH and thermal stability, and efficient cellular uptake. The Pdot barcodes were prepared using a three-color and six-intensity encoding strategy; for ratiometric readout of the barcodes, one of the colors might be used as an internal reference. We used the Pdot barcodes to label 20 sets of cancer cells and then distinguished and identified each set based on the Pdot barcodes using flow cytometry. We also monitored and tracked single cells labeled with different Pdot barcodes, even through rounds of cell division. These results suggest Pdot barcodes are strong candidates for discriminating different labeled cell and for long-term cell tracking.

Skin-safe nanophotosensitizers with highly-controlled synthesized polydopamine shell for synergetic chemo-photodynamic therapy.

Although photodynamic therapy (PDT) has been extensively studied as an established modality of cancer treatment, it still suffers from a few clinical limitations, such as skin phototoxicity and tumor hypoxia. To circumvent these hurdles, hollow silica mesoporous nanoparticles (HMSNs) loaded with photosensitizers were employed as the nanoplatform to construct multifunctional nanoparticles (NPs). Specifically, an ultra-uniform polydopamine (PDA) shell was highly controlled grown around HMSNs by photogenerated outwards-diffused 1O2, followed by conjugation of folic acid-poly(ethylene glycol) and chelation of Fe2+ ions. Thanks to the optimal thickness of light-absorbing PDA shell, the multifunctional NPs exhibited not only negligible skin phototoxicity but also efficient 1O2 generation and photothermal (PT)-enhanced •OH generation upon respective photoirradiation. Anti-tumor therapy was then performed on both 4 T1 tumor cells and tumor-bearing mice by the combination of 638 nm PDT and 808 nm PT-enhanced chemodynamic therapy (CDT). As a result, high therapeutic efficacy was achieved compared to single-modality therapy, with a cell inhibitory rate of 86% and tumor growth inhibition of 70.4% respectively. More interestingly, tumor metastasis was effectively inhibited by the synergetic treatment. These results convincingly demonstrate that our multifunctional NPs are very promising skin-safe PDT agents combined with CDT for efficient tumor therapy.

Facile synthesis of polypyrrole-rhodamine B nanoparticles for self-monitored photothermal therapy of cancer cells.

Photothermal therapy following microscopic temperature detection can avoid overheating effects or insufficient heating, and thus improve therapeutic efficacy. In this study, biocompatible dual-functional nanoparticles (NPs) are constructed from polypyrrole (PPy) and rhodamine B (RB) by a one-step modified polymerization method. The polypyrrole serves as a photothemal agent, and rhodamine B acts as a temperature-sensing probe. The polypyrrole-rhodamine B (PPy-RB) NPs possess a high photothermal effect on irradiation by 808 nm laser, and a competent temperature sensitivity for the real-time temperature monitoring based on the emission intensity response of rhodamine B. After acting on HepG2 cells, the PPy-RB NPs can effectively induce cancer cell death, and the microscopic temperature is monitored by fluorescence feedback from rhodamine B during PTT by laser confocal microscopy. Hence, the proposed approach can supply a facile and promising way for the fabrication of effective theranostic nanoplatforms assisted by self-monitoring of cancer therapeutic processes.

Highly Stable and Luminescent Oxygen Nanosensor Based on Ruthenium-Containing Metallopolymer for Real-Time Imaging of Intracellular Oxygenation.

Metal complex-based luminescent oxygen nanosensors have been intensively studied for biomedical applications. In terms of monitoring dynamics of intracellular oxygen, however, high-quality nanosensors are still badly needed, because of stringent requirements on stability, biocompatibility and luminescence intensity, aside from oxygen sensitivity. In this paper, we reported a type of highly luminescent and stable oxygen nanosensors prepared from metallopolymer. First, a novel ruthenium(II)-containing metallopolymer was synthesized by chelating the oxygen probe [Ru(bpy)3]2+ with a bipyridine-branched hydrophobic copolymer, which was then doped into polymeric nanoparticles (NPs) by a reprecipitation method, followed by further conjugation to selectively target mitochondria (Mito-NPs). The resultant Mtio-NPs possessed a small hydrodynamic size of ∼85 nm, good biocompatibility and high stability resulting from PEGylation and stable nature of Ru-complex. Because the complexed [Ru(bpy)3]2+ homogeneously resided on particle surface, Mito-NPs exhibited strong luminescence at 608 nm that was free of aggregation-caused-quenching, the utmost oxygen sensitivity of free [Ru(bpy)3]2+ probe ( Q = 75%), and linear Stern-Volmer oxygen luminescence quenching plots. Taking advantage of the mitochondria-specific nanosensors, intracellular oxygenation and deoxygenation processes were real-time monitored for 10 min by confocal luminescence imaging, visualized by the gradual weakening (by more than 90%) and enhancing (by 50%) of the red emission, respectively.

Two-photon oxygen nanosensors based on a conjugated fluorescent polymer doped with platinum porphyrins.

Ratiometric fluorescent nanoparticles (NPs) under two-photon excitation are successfully developed for sensing dissolved oxygen. The NPs comprise the oxygen probe Pt(II)-porphyrins (PtTFPP) and fluorescent organic semiconducting polymer (PFO). PFO polymer acts as both a two-photon antenna and a reference dye, while PtTFPP absorbs the photonic energy transferred by the PFO under two-photon excitation at 740 nm to sense oxygen. The red fluorescence of PtTFPP is sensitive to oxygen with a quenching response of 88% from nitrogen saturation to oxygen saturation, and PFO gives oxygen-insensitive referenced blue fluorescence. The fluorescence quenching of the NPs against oxygen at two-photon excitation follows a linear Stern-Volmer behavior. The nanosensors exhibit low cytotoxic effects as well as effortless cellular uptake. When incorporated into cells, the ratio of the signals increases up to about 500% from oxygen-saturated to oxygen-free environment.