Nitric Oxide-Activated Bioorthogonal Codelivery Nanoassembly for In Situ Synthesis of Photothermal Agent for Precise and Safe Anticancer Treatment.

The development of bioorthogonal activation in drug release represents a promising avenue for precise and safe anticancer treatment. However, two significant limitations currently hinder their clinical application: i) the necessity for separate administration of the drug precursor and its corresponding activator, leading to poor drug accumulation and potential side effects; ii) the reliance on exogenous metal or organic activators for triggering bioorthogonal activation, which often exhibit low efficiency and systemic toxicity when extending to living animals. To overcome these limitations, a nitric oxide (NO)-mediated bioorthogonal codelivery nanoassembly, termed TTB-NH2@PArg, which comprises a precursor molecular (TTB-NH2) and amphipathic polyarginine (PArg) is developed. In TTB-NH2@PArg, PArg serves as both self-assembled nanocarrier for TTB-NH2 and a NO generator. In tumor microenvironment (TME), the TME-specific generation of NO acts as a gas activator, triggering in situ bioorthogonal bond formation that transforms TTB-NH2 into TTB-AZO. This tumor-specific generation of TTB-AZO not only serves as a potential photothermal agent for effective tumor inhibition but also induces fluorescence change that enables real-time monitoring of bioorthogonal activation. This study presents a drug codelivery approach that enables precise and safe control of bioorthogonal activation for anticancer treatment, improving cancer therapy efficacy while minimizing side effects.

Thymoquinone as an electron transfer mediator to convert Type II photosensitizers to Type I photosensitizers.

The development of Type I photosensitizers (PSs) is of great importance due to the inherent hypoxic intolerance of photodynamic therapy (PDT) in the hypoxic microenvironment. Compared to Type II PSs, Type I PSs are less reported due to the absence of a general molecular design strategy. Herein, we report that the combination of typical Type II PS and natural substrate carvacrol (CA) can significantly facilitate the Type I pathway to efficiently generate superoxide radical (O2-•). Detailed mechanism study suggests that CA is activated into thymoquinone (TQ) by local singlet oxygen generated from the PS upon light irradiation. With TQ as an efficient electron transfer mediator, it promotes the conversion of O2 to O2-• by PS via electron transfer-based Type I pathway. Notably, three classical Type II PSs are employed to demonstrate the universality of the proposed approach. The Type I PDT against S. aureus has been demonstrated under hypoxic conditions in vitro. Furthermore, this coupled photodynamic agent exhibits significant bactericidal activity with an antibacterial rate of 99.6% for the bacterial-infection female mice in the in vivo experiments. Here, we show a simple, effective, and universal method to endow traditional Type II PSs with hypoxic tolerance.

Programmable Singlet Oxygen Battery for Automated Photodynamic Therapy Enabled by Pyridone-Pyridine Tautomer Engineering.

The efficacy of photodynamic therapy is hindered by the hypoxic environment in tumors and limited light penetration depth. The singlet oxygen battery (SOB) has emerged as a promising solution, enabling oxygen- and light-independent 1O2 release. However, conventional SOB systems typically exhibit an "always-ON" 1O2 release, leading to potential 1O2 leakage before and after treatment. This not only compromises therapeutic outcomes but also raises substantial biosafety concerns. In this work, we introduce a programmable singlet oxygen battery, engineered to address all the issues discussed above. The concept is illustrated through the development of a tumor-microenvironment-responsive pyridone-pyridine switch, PyAce, which exists in two tautomeric forms: PyAce-0 (pyridine) and PyAce (pyridone) with different 1O2 storage half-lives. In its native state, PyAce remains in the pyridone form, capable of storing 1O2 (t1/2 = 18.5 h). Upon reaching the tumor microenvironment, PyAce is switched to the pyridine form, facilitating rapid and thorough 1O2 release (t1/2 = 16 min), followed by quenched 1O2 release post-therapy. This mechanism ensures suppressed 1O2 production pre- and post-therapy with selective and rapid 1O2 release at the tumor site, maximizing therapeutic efficacy while minimizing side effects. The achieved "OFF-ON-OFF" 1O2 therapy showed high spatiotemporal selectivity and was independent of the oxygen supply and light illumination.

Oxygen-independent organic photosensitizer with ultralow-power NIR photoexcitation for tumor-specific photodynamic therapy.

Photodynamic therapy (PDT) is a promising cancer treatment but has limitations due to its dependence on oxygen and high-power-density photoexcitation. Here, we report polymer-based organic photosensitizers (PSs) through rational PS skeleton design and precise side-chain engineering to generate •O2- and •OH under oxygen-free conditions using ultralow-power 808 nm photoexcitation for tumor-specific photodynamic ablation. The designed organic PS skeletons can generate electron-hole pairs to sensitize H2O into •O2- and •OH under oxygen-free conditions with 808 nm photoexcitation, achieving NIR-photoexcited and oxygen-independent •O2- and •OH production. Further, compared with commonly used alkyl side chains, glycol oligomer as the PS side chain mitigates electron-hole recombination and offers more H2O molecules around the electron-hole pairs generated from the hydrophobic PS skeletons, which can yield 4-fold stronger •O2- and •OH production, thus allowing an ultralow-power photoexcitation to yield high PDT effect. Finally, the feasibility of developing activatable PSs for tumor-specific photodynamic therapy in female mice is further demonstrated under 808 nm irradiation with an ultralow-power of 15 mW cm-2. The study not only provides further insights into the PDT mechanism but also offers a general design guideline to develop an oxygen-independent organic PS using ultralow-power NIR photoexcitation for tumor-specific PDT.

Phototunable and Photopatternable Polymer Semiconductors.

ConspectusIn recent decades, there has been rapid development in the field of polymer semiconductors, particularly those based on conjugated donor-acceptor (D-A) polymers exhibiting high charge mobilities. Furthermore, the application of polymer semiconductors has been successfully extended to a wide range of functional devices, including sensors, photodetectors, radio frequency identification (RFID) tags, electronic paper, skin electronics, and artificial synapses. Over the past few years, there has been a growing focus on stimuli-responsive polymer semiconductors, which have the potential to impart additional functionalities to conventional field-effect transistors, garnering increased attention within the research community. In this context, phototunable polymer semiconductors have received significant attention due to their ability to utilize light as an external stimulus, enabling remote control of device performance with high spatiotemporal resolution. Meanwhile, integration of field-effect transistors with polymer semiconductors can enable the realization of complex functions. To achieve this, precise and controllable patterning of polymer semiconductors becomes essential. In this Account, we discuss our research findings in the context of phototunable and photopatternable polymer semiconductors. These developments encompass the following key aspects: (i) polymer semiconductors, such as poly(diketopyrrolopyrrole-quaterthiophene) (PDPP4T), exhibit phototunability when blended with the photochromic compound hexaarylbiimidazole (HABI). The photo/thermal-responsive field-effect transistors (FETs) can be fabricated using blending thin films. Remarkably, these photo/thermal-responsive transistors can function as photonically programmable and thermally erasable nonvolatile memory devices. (ii) By incorporating photoswitchable groups like azo and spiropyran into the side chains of conjugated D-A polymers, we can create phototunable polymer semiconductors. The reversible isomerization of azo and spiropyran groups significantly influences the charge transport properties of these polymer semiconductors. Consequently, the performance of the resulting FETs can be reversibly tuned through UV/visible or near-infrared light (NIR) irradiation. Notably, the incorporation of two distinct azo groups into the side chains leads to polymer semiconductors with tristable semiconducting states, offering the ability to logically control device performance using light irradiation at three different wavelengths. (iii) Photopatterning of p-type, n-type, and ambipolar semiconductors featuring alkyl side chains can be achieved using a diazirine-based, four-armed photo-cross-linker (4CNN) with a loading concentration of no more than 3% (w/w). Furthermore, the semiconducting performances of FETs with patterned thin films were found to be satisfactorily uniform. Importantly, the cross-linked thin films are robust and show good resistance to organic solvents, which is useful for fabricating all-solution processable multilayer electronic devices. (iv) The introduction of azide groups into the side chains of conjugated polymers results in a single-component semiconducting photoresist. The presence of azide groups renders the side chains with photo-cross-linking ability, enabling the successful formation of uniform patterns, even as small as 5 µm, under UV light irradiation. Benefiting from the single component feature, field-effect transistors with individual patterned thin films display satisfactorily uniform performances. Moreover, this semiconducting photoresist has proven effective for efficiently photopatterning other polymer semiconductors, demonstrating its versatility.

Activatable Type I Photosensitizer with Quenched Photosensitization Pre and Post Photodynamic Therapy.

The phototoxicity of photosensitizers (PSs) pre and post photodynamic therapy (PDT), and the hypoxic tumor microenvironment are two major problems limiting the application of PDT. While activatable PSs can successfully address the PS phototoxicity pre PDT, and type I PS can generate reactive oxygen species (ROS) effectively in hypoxic environment, very limited approaches are available for addressing the phototoxicity post PDT. There is virtually no solution available to address all these issues using a single design. Herein, we propose a proof-of-concept on-demand switchable photosensitizer with quenched photosensitization pre and post PDT, which could be activated only in tumor hypoxic environment. Particularly, a hypoxia-normoxia cycling responsive type I PS TPFN-AzoCF3 was designed to demonstrate the concept, which was further formulated into TPFN-AzoCF3 nanoparticles (NPs) using DSPE-PEG-2000 as the encapsulation matrix. The NPs could be activated only in hypoxic tumors to generate type I ROS during PDT treatment, but remain non-toxic in normal tissues, pre or after PDT, thus minimizing side effects and improving the therapeutic effect. With promising results in in vitro and in vivo tumor treatment, this presented strategy will pave the way for the design of more on-demand switchable photosensitizers with minimized side effects in the future.

Encapsulation of Dual-Passivated Perovskite Quantum Dots for Bio-Imaging.

Due to their marvelous electrical and optical properties, perovskite nanocrystals have reached remarkable landmarks in solar cells, light-emitting diodes, and photodetectors. However, the intrinsic instability of ionic perovskites, which would undergo an undesirable phase transition and decompose rapidly in ambient humidity, limits their long-term practical deployment. To address this challenge, halogenated trimethoxysilane as the passivation additive is chosen, which utilizes simultaneous halide and silica passivation to enhance the stability of perovskite nanoparticles via a dual-passivation mechanism. The processable nanoparticles show high photoluminescence quantum yield, tunable fluorescence wavelength, and excellent resistance against air and water, highlighting great potential as green to deep-red bio-labels after further phospholipid encapsulation. This work demonstrates that the dual-passivation mechanism could be used to maintain the long-term stability of ionic crystals, which sheds light on the opportunity of halide perovskite nanoparticles for usage in a humid environment.

Simultaneous Incorporation of Two Types of Azo-Groups in the Side Chains of a Conjugated D-A Polymer for Logic Control of the Semiconducting Performance by Light Irradiation.

A new design strategy for photoresponsive semiconducting polymer with tri-stable semiconducting states is reported by simultaneous incorporation of tetra-ortho-methoxy-substituted azobenzene (mAzo) and arylazopyrazole (pAzo) in the side chains. The trans-to-cis transformations for mAzo and pAzo groups can sequentially occur within the polymer thin film after sequential 560 and 365 nm light irradiation. Remarkably, the trans-cis isomerization of mAzo and pAzo groups can modulate the thin film crystallinity. Accordingly, the performances of the resulting field-effect transistors (FETs) can be reversibly modulated, leading to tri-stable semiconducting states after sequential 560, 365, and 470 nm light irradiation. Therefore, the device performance can be logically controlled by light irradiation at three different wavelengths. In addition, with light irradiation and device current as the input and output signals, the three-value logic gate by using single FET device can be successfully mimicked.

Unconventional Transformation of the Two Carbonyl Groups in 4,4',5,5'-Tetrachloro-10H,10'H-[9,9'-bianthracenylidene]-10,10'-dione into Diallenes.

The diallene-containing compound dACl-1 was unexpectedly obtained by the unconventional transformation of two carbonyl groups in 4,4',5,5'-tetrachloro-10H,10'H-[9,9'-bianthracenylidene]-10,10'-dione into diallenes. In addition, the two 1-triisopropylsilyl (TIPS) groups in dACl-1 were easily removed to yield dACl-2. The reaction mechanism was investigated and is discussed. Moreover, both compounds are stable under ambient conditions, and, in particular, dACl-1 is thermally stable at 315 °C.

A Conjugated Polymer Containing Arylazopyrazole Units in the Side Chains for Field-Effect Transistors Optically Tunable by Near Infra-Red Light.

Optically tunable field-effect transistors (FETs) with near infra-red (NIR) light show promising applications in various areas. Now, arylazopyrazole groups are incorporated in the side chains of a semiconducting donor-acceptor (D-A) polymer. The cis-trans interconversion of the arylazopyrazole can be controlled by 980 nm and 808 nm NIR light irradiation, by utilizing NaYF4 :Yb,Tm upconversion nanoparticles and the photothermal effect of conjugated D-A polymers, respectively. This reversible transformation affects the interchain packing of the polymer thin film, which in turn reversibly tunes the semiconducting properties of the FETs by the successive 980 nm and 808 nm light irradiation. The resultant FETs display fast response to NIR light, good resistance to photofatigue, and stability in storage for up to 120 days. These unique features will be useful in future memory and bioelectronic wearable devices.

Photo-/Thermal-Responsive Field-Effect Transistor upon Blending Polymeric Semiconductor with Hexaarylbiimidazole toward Photonically Programmable and Thermally Erasable Memory Device.

It is shown that the semiconducting performance of field-effect transistors (FETs) with PDPP4T (poly(diketopyrrolopyrrole-quaterthiophene)) can be reversibly tuned by UV light irradiation and thermal heating after blending with the photochromic hexaarylbiimidazole compound (p-NO2 -HABI). A photo-/thermal-responsive FET with a blend thin film of PDPP4T and p-NO2 -HABI is successfully fabricated. The transfer characteristics are altered significantly with current enhanced up to 106 -fold at VG = 0 V after UV light irradiation. However, further heating results in the recovery of the transfer curve. This approach can be extended to other semiconducting polymers such as P3HT (poly(3-hexyl thiophene)), PBTTT (poly(2,5-bis(3-tetradecylthiophen-2-yl)thieno[3,2-b] thiophene)) and PDPPDTT (poly(diketopyrrolopyrrole-dithienothiophene)). It is hypothesized that TPIRs (2,4,5-triphenylimidazolyl radicals) formed from p-NO2 -HABI after UV light irradiation can interact with charge defects at the gate dielectric-semiconductor interface and those in the semiconducting layer to induce more hole carriers in the semiconducting channel. The application of the blend thin film of PDPP4T and p-NO2 -HABI is further demonstrated to fabricate the photonically programmable and thermally erasable FET-based nonvolatile memory devices that are advantageous in terms of i) high ON/OFF current ratio, ii) nondestructive reading at low electrical bias, and iii) reasonably highly stable ON-state and OFF-state.

Multiple Anti-Counterfeiting Guarantees from a Simple Tetraphenylethylene Derivative - High-Contrasted and Multi-State Mechanochromism and Photochromism.

Herein the novel tetraphenylethylene (TPE) derivative 1 was designed with an integration of aggregation-induced emission (AIE), multi-state mechanochromism and self-recovery photochromism. The molecule was susceptible to grinding, heating and vapor fuming and showed corresponding transition of its emission colors. The heated powder or single crystal of 1 exhibited reversible photochromism. After a short period of UV irradiation, it showed a bright red color, but recovered to its original white appearance within 1 min. The photochromism is due to the formation of photocyclization intermediates upon UV irradiation, while the eversible mechanochromism is attributed to the weak molecular interactions derived from head-to-tail stacking of the molecules. This reversible multi-state, high-contrasted and rapid responsive mechanochromic and photochromic property cooperatively provide double enhancement of a multimode guarantee in advanced anti-counterfeiting.

Improving the Electronic Transporting Property for Flexible Field-Effect Transistors with Naphthalene Diimide-Based Conjugated Polymer through Branching/Linear Side-Chain Engineering Strategy.

n-Type organic/polymeric semiconductors with high electron mobilities are highly demanded for future flexible organic circuits. Except for developing a new conjugated backbone, recent studies show that side-chain engineering also plays an indispensable role in boosting the charge-transporting property. In this paper, we report a new polymer PNDI2T-DTD with a representative n-type naphthalene diimide (NDI)-bithiophene backbone for high-performance n-type flexible thin-film transistors through branching/linear side-chain engineering strategy. Serving as the flexible side chains, the linear/branching side-chain pattern is found to be effective in tuning the preaggregation behavior in solution and the packing ordering of polymeric chains, resulting in the improvement of thin-film crystallinity. The electron mobility of the thin film of PNDI2T-DTD on flexible substrates can reach 1.52 cm2 V-1 s-1, which is approximately five times higher than that of PNDI2T-DT with the same conjugated backbone and only branching alkyl chains.

Tuning the Photoinduced Electron Transfer in a Zr-MOF: Toward Solid-State Fluorescent Molecular Switch and Turn-On Sensor.

The immobilization of fluorescent photoinduced electron transfer (PET) switches/sensors into solid state, which usually cannot maintain their identical properties in solution, has remained a big challenge. Herein, a water-stable anthracene and maleimide appended zirconium-based-metal-organic framework (Zr-MOF; UiO-68-An/Ma) is reported. Unlike the regular intramolecular "fluorophore-spacer-receptor" format, the separated immobilization of fluorescent (anthracene) and acceptor (maleimide) groups into the framework of a multivariate MOF can also favor a pseudo-intramolecular fluorescent PET process, resulting in UiO-68-An/Ma with very weak fluorescence. Interestingly, after Diels-Alder reaction or thiol-ene reaction of maleimide groups, the pseudo-intramolecular fluorescent PET process in UiO-68-An/Ma fails and the solid-state fluorescence of the crystals is recovered. In addition, UiO-68-An/Ma shows an interesting application as solid-state fluorescent turn-on sensor for biothiols, with the naked eye response at a low concentration of 50 µmol L-1 within 5 min. This study represents a general strategy to enable the efficient tuning of fluorescent PET switches/sensors in solid state, and considering the fluorescence of the PET-based MOFs can be restored after addition of analyte/target species, this research will definitely inspire to construct stimuli-responsive fluorescent MOFs for interesting applications (e.g., logic gate) in future.