Benzobisthiadiazole-Based Small Molecular Near-Infrared-II Fluorophores: From Molecular Engineering to Nanophototheranostics.

Organic fluorescent molecules with emission in the second near-infrared (NIR-II) biological window have aroused increasing investigation in cancer phototheranostics. Among these studies, Benzobisthiadiazole (BBT), with high electron affinity, is widely utilized as the electron acceptor in constructing donor-acceptor-donor (D-A-D) structured fluorophores with intensive near-infrared (NIR) absorption and NIR-II fluorescence. Until now, numerous BBT-based NIR-II dyes have been employed in tumor phototheranostics due to their exceptional structure tunability, biocompatibility, and photophysical properties. This review systematically overviews the research progress of BBT-based small molecular NIR-II dyes and focuses on molecule design and bioapplications. First, the molecular engineering strategies to fine-tune the photophysical properties in constructing the high-performance BBT-based NIR-II fluorophores are discussed in detail. Then, their biological applications in optical imaging and phototherapy are highlighted. Finally, the current challenges and future prospects of BBT-based NIR-II fluorescent dyes are also summarized. This review is believed to significantly promote the further progress of BBT-derived NIR-II fluorophores for cancer phototheranostics.

Asymmetric aza-BODIPY photosensitizer for photoacoustic/photothermal imaging-guided synergistic photodynamic/photothermal therapy.

Cancer synergistic therapy usually shows improved therapeutic efficacy with low side effects. In this contribution, an aza-BODIPY-derived photosensitizer NBDP with asymmetric structure and the periphery phenyl ring modified with bromine atom was designed and synthesized for synergistic photothermal therapy (PTT) and photodynamic therapy (PDT). Photosensitizer NBDP exhibited good singlet oxygen (1O2) generation capacity (1.43 times higher than that of ICG), and NBDP NPs showed an outstanding photothermal conversion efficiency (η) of 46.0% under 660 nm photoirradiation. Guided by in vivo photoacoustic (PA) imaging, NBDP NPs were found to targetedly accumulate in the tumor tissues in 6 h. All results showed that the aza-BODIPY-derived photosensitizer NBDP had great potential for PA/photothermal imaging-guided synergistic PTT/PDT.

Potent nanoreactor-mediated ferroptosis-based strategy for the reversal of cancer chemoresistance to Sorafenib.

The drug resistance of cancer cells is related to a variety of mechanisms, among which the destruction of redox homeostasis is one of the key factors. Ferroptosis, an intracellular iron-dependent form of cell death, is related to the production of oxidative stress. The accumulation of lipid peroxidation (LPO) during ferroptosis disrupts intracellular redox homeostasis, thereby affecting the sensitivity of tumor cells to drugs. In this work, we proposed a ferroptosis strategy based on LPO accumulation, reduced glutathione generation via inhibition of SLC3A2 protein and inactivated glutathione peroxidase 4 (GPX4) to reverse the chemoresistance of cancer cells. The Fenton reaction based on the ferroptosis-inducing nanoreactors (Au/Fe-GA/Sorafenib@PEG) not only generated hydroxyl radicals (·OH) under laser irradiation to realize the accumulation of LPO, but also depleted GSH to increase the accumulation of LPO. Meanwhile, the cystine uptake of cells was inhibited by Sorafenib, resulting in reduced GSH synthesis and inactivated GPX4. In vitro and in vivo experiments demonstrated AFG/SFB@PEG + Laser group could inactivate GPX4 and the enhanced ferroptosis can reverse chemo-resistance caused by continuous upregulation of GPX4 levels in cells through 'self-rescue'. The study proposed the mechanism and feasibility of ferroptosis to reverse drug resistance, providing a promising strategy for chemo-resistant cancer treatment. STATEMENT OF SIGNIFICANCE: Herein, we proposed a ferroptosis strategy based on LPO accumulation, reduced glutathione generation via inhibition of SLC3A2 protein, and inactivated glutathione peroxidase 4 (GPX4) to reverse chemoresistance of cancer cells. The Fenton reaction based on the ferroptosis-inducing nanoreactors (Au/Fe-GA/Sorafenib@PEG) not only generated hydroxyl radicals (·OH) under laser irradiation to realize the accumulation of LPO but also depleted GSH to increase the accumulation of LPO. Meanwhile, the cystine uptake of cells was inhibited by Sorafenib, resulting in reduced GSH synthesis and inactivated GPX4. In vitro and in vivo experiments demonstrated AFG/SFB@PEG + Laser group could inactivate GPX4 and the enhanced ferroptosis can reverse chemo-resistance caused by continuous upregulation of GPX4 levels in cells through 'self-rescue'.

Hijacking the self-replicating machine of bacteriophage for PCR-based cascade signal amplification in detecting SARS-CoV-2 viral marker protein in serum.

In this work, the nucleic acid detection of SARS-Cov-2 is extended to protein markers of the virus, utilizing bacteriophage. Specifically, the phage display technique enables the main protease of SARS-Cov-2 to control the self-replication of m13 phage, so that the presence of the viral protease can be amplified by phage replication as the first round of signal amplification. Then, the genome of replicated phage can be detected using polymer chain reaction (PCR), as the second round of signal amplification. Based on these two types of well-established biotechnology, the proposed method shows satisfactory sensitivity and robustness in the direct serum detection of the viral protease. These results may point to clinical application in the near future.

Recent Nanotechnologies to Overcome the Bacterial Biofilm Matrix Barriers.

Bacterial biofilm-related infectious diseases severely influence human health. Under typical situations, pathogens can colonize inert or biological surfaces and form biofilms. Biofilms are functional aggregates that coat bacteria with extracellular polymeric substances (EPS). The main reason for the failure of biofilm infection treatment is the low permeability and enrichment of therapeutic agents within the biofilm, which results from the particular features of biofilm matrix barriers such as negatively charged biofilm components and highly viscous compact EPS structures. Hence, developing novel therapeutic strategies with enhanced biofilm penetrability is crucial. Herein, the current progress of nanotechnology methods to improve therapeutic agents' penetrability against biofilm matrix, such as regulating material morphology and surface properties, utilizing the physical penetration of nano/micromotors or microneedle patches, and equipping nanoparticles with EPS degradation enzymes or signal molecules, is first summarized. Finally, the challenges, perspectives, and future implementations of engineered delivery systems to manage biofilm infections are presented in detail.

Ultrasonic-Induced Synthesis of Underwater Adhesive and Antiswelling Hydrogel for Strain Sensor.

To perceive the human body's multienvironmental mobility, intelligent flexible electronic equipment with an underwater motion monitoring function has potential research value in the field of intelligent detection. Hydrogels are widely used in the field of flexible electronics for their unique three-dimensional polymer networks. Due to the instinctive hydrophilicity of hydrogels, the swelling of hydrogels underwater and the formation of hydration coating on the surface become the primary obstacles to underwater applications. Herein, a hydrogel sensor that can achieve underwater utilization was prepared through copolymerization between hydrophobic and hydrophilic polymer monomers. The synergistic impact of electrostatic interaction, metal coordination, and hydrogen bonding ensured the hydrogel's remarkable underwater adhesive ability to a variety of substrates. The hydrophobic micelles and self-hydrophobization process induced from ultrasonic dispersion in the polymer matrix gave an outstanding hydrophobic performance (water contact angle of 130.4°) and antiswelling property (swelling ratio of 26% after 72 h of immersion), presenting unprecedented underwater adaptability. The above-mentioned hydrogel could be assembled into a flexible hydrogel sensor with satisfactory sensitivity (gauge factor of 0.44), ultrafast response rate (106 ms), and excellent cyclic stability, demonstrating accurate monitoring of complex human motions in water and air.

A recyclable self-supported nanoporous PdCu heterogeneous catalyst for aqueous Suzuki-Miyaura cross-coupling.

Nanoporous PdCu (NP-PdCu) was prepared by the dealloying strategy from a PdCuAl ternary alloy precursor and characterized systematically using SEM, TEM, XRD, and XPS. NP-PdCu was demonstrated to be a competent self-supported heterogenous catalyst for Suzuki-Miyaura cross-coupling, affording a series of synthetically valuable biaryl compounds in good to excellent yields. This catalyst could be easily separated from the product via centrifugation and reused several times without obvious loss of catalytic performance.