Polymer Dots with Delayed Fluorescence and Tunable Cellular Uptake for Photodynamic Therapy and Time-Gated Imaging.

By combining bioimaging and photodynamic therapy (PDT), it is possible to treat cancer through a theranostic approach with targeted action for minimum invasiveness and side effects. Thermally activated delayed fluorescence (TADF) probes have gained recent interest in theranostics due to their ability to generate singlet oxygen (1O2) while providing delayed emission that can be used in time-gated imaging. However, it is still challenging to design systems that simultaneously show (1) high contrast for imaging, (2) low dark toxicity but high phototoxicity and (3) tunable biological uptake. Here, we circumvent shortcomings of TADF systems by designing block copolymers and their corresponding semiconducting polymer dots (Pdots) that encapsulate a TADF dye in the core and expose an additional boron-dipyrromethene (BODIPY) oxygen sensitizer in the corona. This architecture provides orange-red luminescent particles (ΦPL up to 18 %) that can efficiently promote PDT (1O2 QY=42 %) of HeLa cells with very low photosensitizer loading (IC50 ~0.05-0.13 µg/mL after 30 min). Additionally, we design Pdots with tunable cellular uptake but similar PDT efficiencies using either polyethylene glycol or guanidinium-based coronas. Finally, we demonstrate that these Pdots can be used for time-gated imaging to effectively filter out background fluorescence from biological samples and improve image contrast.

Redox-Active Heteroatom-Functionalized Polyacetylenes.

The discovery of metallic conductivity in polyacetylene [-HC=CH-]n upon doping represents a landmark achievement. However, the insolubility of polyacetylene and a dearth of methods for its chemical modification have limited its widespread use. Here, we employ a ring-opening metathesis polymerization (ROMP) protocol to prepare functionalized polyacetylenes (fPAs) bearing: (1) electron-deficient boryl (-BR2 ) and phosphoryl (-P(O)R2 ) side chains; (2) electron-donating amino (-NR2 ) groups, and (3) ring-fused 1,2,3-triazolium units via strain-promoted Click chemistry. These functional groups render most of the fPAs soluble and can lead to intense light absorption across the visible to near-IR region. Also, the presence of redox-active boryl and amino groups leads to opposing near-IR optical responses upon (electro)chemical reduction or oxidation. Some of the resulting fPAs show greatly enhanced air stability when compared to known polyacetylenes. Lastly, these fPAs can be cross-linked to yield network materials with the full retention of optical properties.

Organelle-Targeting Polymer Dots Exhibiting Thermally Activated Delayed Fluorescence for Subcellular Imaging.

Selective imaging of specific subcellular structures provides valuable information about the cellular microenvironment. Materials exhibiting thermally activated delayed fluorescence (TADF) are rapidly emerging as metal-free probes with long-lived emission for intracellular time-gated imaging applications. Polymers incorporating TADF emitters can self-assemble into luminescent nanoparticles, termed polymer dots (Pdots), and this strategy enables them to circumvent the limitations of commercial organelle trackers and small molecule TADF emitters. In this study, diblock copolymers comprised of a hydrophilic block containing organelle-targeting monomers and a hydrophobic TADF-active block were synthesized by ring-opening metathesis polymerization (ROMP). Oxanorbornene-based monomers incorporating morpholine and triphenylphosphonium groups for lysosome and mitochondria targeting, respectively, were also synthesized. ROMP by sequential addition yielded well-defined diblock copolymers with dispersities <1.28. To analyze the effect of tuning the hydrophilic corona on cellular viability and uptake, we prepared Pdots with poly(ethylene glycol) (PEG) and bis-guanidinium (BGN) coronas, resulting in limited and efficient cellular uptake, respectively. Red-emissive Pdots with BGN-based coronas and organelle-targeting functionality were obtained with quantum yields up to 12% in water under air. Colocalization analysis confirmed that lysosome and mitochondria labeling in live HeLa cells was accomplished within 2 h of incubation, affording Pearson's correlation coefficients of 0.37 and 0.70, respectively. The potential application of these Pdots for time-resolved imaging is highlighted by a proof of concept using time-gated spectroscopy, which effectively separates the delayed emission of the TADF Pdots from the background autofluorescence of biological serum.

Rapid access to (cycloalkyl)tellurophene oligomer mixtures and the first poly(3-aryltellurophene).

Polytellurophenes represent an emerging class of π-conjugated polymers that possess important characteristics for flexible electronics, such as narrow HOMO-LUMO gaps (Eg) and charge mobilities that can be orders of magnitude larger than their ubiquitous polythiophene counterparts. Herein we use the reactivity of pinacolboronate (BPin) groups attached to tellurophene scaffolds to directly prepare new 2,5-diiodinated monomers, which are then polymerized to afford new low Eg oligomers and polymers. Specifically, mixtures of (cycloalkyl)tellurophene oligomers (of 5 to 12 repeat units) with ring-fused 5- and 6-membered cyclic side chains were prepared via Yamamoto coupling, with a dramatic narrowing of band gap noted when less bulky 5-membered cycloalkyl side groups were present, due to enhanced tellurophene ring coplanarity. Grignard metathesis (GRIM) was also used to gain access to the first poly(3-aryltellurophene) with 94% regioregularity, along with a low Eg of 1.3 eV and an onset of light absorption at ca. 1000 nm.