Coupling Chlorin-Based Photosensitizers and Histone Deacetylase Inhibitors for Photodynamic Chemotherapy.

Photodynamic therapy combined with chemotherapy is a promising strategy to improve the antitumor efficacy. On the basis of coupling the chlorin-based photosensitizer pyropheophorbide a (Pyro) and histone deacetylase inhibitors (HDACis) to fabricate dual-mode antitumor molecules, a series of dual-mode antitumor prodrug molecules were synthesized and assessed for antitumor activity in vitro and in vivo. The data demonstrated that compound 4, with the most favorable phototoxicity and dark toxicity, could significantly inhibit the cell migration and upregulate the expression of acetyl-H3 protein, functioning as a photosensitizer and HDACi, respectively. Furthermore, compared with talaporfin, Pyro, and SAHA, compound 4 demonstrated the best inhibitory effect on tumor growth and metastasis in tumor-bearing mice; therefore, represented by compound 4, this pharmacophore coupling strategy is much more promising and effective than the pharmacophore fusion strategy for fabricating photodynamic and chemotherapeutical dual-mode molecules.

Modulating the Electron-Donating Ability of Acridine Donor Units for Orange-Red Thermally Activated Delayed Fluorescence Emitters.

The development of thermally activated delayed fluorescence (TADF) emitters with orange-red emission still lags behind that of their blue, green, and yellow counterparts. Recent research to address this problem mainly focused on developing new acceptor units. There were few donor units designed especially for orange-red emitters. Herein, with benzothiophene fused to a diphenylacridine donor unit, a new donor moiety, namely, 5,5-diphenyl-5,13-dihydrobenzo[4,5]thieno[3,2-c]acridine (BTDPAc), was designed and synthesized. Benefiting from the strong electron-donating ability of the new donor moiety, a new TADF emitter, 2-[4'-(tert-butyl)(1,1'-biphenyl)-4-yl]-6-[5,5-diphenylbenzo[4,5]thieno[3,2-c]acridin-13(5H)-yl]-1H-benzo[de]isoquinoline-1,3(2H)-dione (BTDPAc-PhNAI), shows an orange-red emission with a maximum at 610 nm in dilute toluene solution. Also, with the help of the diphenyl rings of the donor unit, high photoluminescence quantum yields were achieved for BTDPAc-PhNAI over a wide concentration range. Consequently, an orange-red organic light-emitting diode based on BTDPAc-PhNAI achieved a high external quantum efficiency of nearly 20 %, which was comparable to state-of-the-art device performances with similar emission spectra.

Adamantane-based wide-bandgap host material: blue electrophosphorescence with high efficiency and very high brightness.

An adamantane-based host material, namely, 4-{3-[4-(9H-carbazol-9-yl)phenyl]adamantan-1-yl}benzonitrile (CzCN-Ad), was prepared by linking an electron-donating carbazole unit and an electron-accepting benzonitrile moiety through an adamantane bridge. In this approach, two functional groups were attached to tetrahedral points of adamantane to construct an "sp(3)" topological configuration. This design strategy endows the host material with a high triplet energy of 3.03 eV due to the disruption of intramolecular charge transfer. Although CzCN-Ad has a low molecular weight, the rigid nonconjugated adamantane bridge results in a glass transition temperature of 89 °C. These features make CzCN-Ad suitable for fabricating blue phosphorescent organic light-emitting diodes (PhOLEDs). The devices based on sky-blue phosphor bis[(4,6-difluorophenyl)pyridinato-N,C(2')](picolinato)iridium(III) (FIrpic) achieved a high maximum external quantum efficiency (EQE) of 24.1%, which is among the best results for blue PhOLEDs ever reported. Furthermore, blue PhOLEDs with bis(2,4-difluorophenylpyridinato)-tetrakis(1-pyrazolyl)borate iridium(III) (FIr6) as dopant exhibited a maximum EQE of 14.2% and a maximum luminance of 34 262 cd m(-2). To the best of our knowledge, this is the highest luminance ever reported for FIr6-based PhOLEDs.

Chidamide stacked in magnetic polypyrrole nano-composites counter thermotolerance and metastasis for visualized cancer photothermal therapy.

Photothermal therapy (PTT) has become one of the most promising therapies in cancer treatment as its noninvasiveness, high selectivity, and favorable compliance in clinic. However, tumor thermotolerance and distal metastasis reduce its efficacy, becoming the bottleneck of applying PTT in clinic. In this study, a chidamide-loaded magnetic polypyrrole nanocomposite (CMPP) has been fabricated as a visualized cancer photothermal agent (PTA) to counter tumor thermotolerance and metastasis. The efficacy of CMPP was characterized by in vitro and in vivo assays. As a result, this kind of magnetic polypyrrole nanocomposites were black spherical nanoparticles, possessing a favorable photothermal effect and the suitable particle size of 176.97 ± 1.45 nm with a chidamide loading rate of 12.92 ± 0.45%. Besides, comparing with PTT, CMPP exhibited significantly higher cytotoxicity and cellular apoptosis rate in two tumor cell lines (B16-F10 and HepG2). In vivo study, the mice showed obvious near-infrared (NIR) and magnetic resonance imaging (MRI) dual-modal imaging at tumor sites and sentinel lymph nodes (SLNs); on the other hand, magnetic targeting guided CMPP achieved a cure level on melanoma-bearing mice through preventing metastasis and thermotolerance. Overall, with high loading efficiency of chidamide and strong magnetic targeting to tumor sites and SLNs, CMPP could significantly raise efficiency of PTT by targeting tumor thermotolerance and metastasis, and this strategy may be exploited therapeutically to upgrade PTT with MPP as one of appropriate carriers for histone deacetylase inhibitors (HDACis).

Lysosomal activable Vorinostat carrier-prodrug self-assembling with BPQDs enables photothermal oncotherapy to reverse tumor thermotolerance and metastasis.

Photothermal therapy (PTT) is becoming increasing prevalent in clinic for eradicating the primary tumor and improving cancer patients' compliance. However, photothermal resistance and distal metastasis still haunt the tumor treatment with PTT. Herein, on the basis that histone deacetylase acetylase inhibitor (HDACis) could activate the expression of anti-tumor gene and accelerate the differentiation and apoptosis of tumor cells, we propose that HDACis supplementing PTT could overcome those obstacles with appropriate drug-controlled release strategy. Thus, we fabricated a nano-complex of lysosomal activable vorinostat (SAHA) carrier-prodrug encapsulating black phosphorus quantum dots (BPQDs@PPS) to counter those challenges in PTT. With spherical morphology and favorable bio-safety, BPQDs@PPS could release BPQDs and Vorinostat spontaneously in lysosome, not only effectively inhibiting tumor growth, but also reversing tumor thermotolerance and metastasis within a PTT procedure. Especially, both western blot and immunofluorescence analysis validate that Vorinostat enables PTT to reverse tumor thermotolerance and distal metastasis by down-regulation of HSP70 and up-regulation of H3. Therefore, this research not only reveals the mechanism how HDACis supplement PTT in reversing tumor thermotolerance and metastasis, but also provides a promising prospect to upgrade clinical photothermal therapy.

Inheriting the Characteristics of TADF Small Molecule by Side-Chain Engineering Strategy to Enable Bluish-Green Polymers with High PLQYs up to 74% and External Quantum Efficiency over 16% in Light-Emitting Diodes.

Thermally activated delayed fluorescence (TADF) polymers are designed and synthesized by grafting the TADF emitter to the side chain of the polycarbazole backbone. By employing these TADF polymers with large ratio of delayed fluorescence component and high photoluminescence quantum yield as the emitters, the solution-processed light-emitting diodes achieve a maximal external quantum efficiency of 16.1% at a luminance of around 100 cd m-2 .

Creating a thermally activated delayed fluorescence channel in a single polymer system to enhance exciton utilization efficiency for bluish-green electroluminescence.

We designed and synthesized a single polymer with TADF characteristics by grafting the TADF emitter, 10-(4-(5-phenyl-1,3,4-oxadiazol-2-yl)phenyl)-10H-phenoxazine, onto the side chain of the polymer backbone of polycarbazole. Employing these copolymers as emitting layers, an efficient bluish-green polymer LED with a maximum external quantum efficiency of 4.3% was achieved, corresponding to a high exciton utilization efficiency (EUE) of 63.7%.