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A broad-spectrum polymeric antimicrobial, PEoS-PHMG, was developed to achieve dual-modality bacterial inhibition viaphotodynamic inactivation and physical damage. Compared with native PHMG, current photosensitizer conjugate-functionalized PHMG exhibited excellent bacterial inhibition and enhanced biocompatibility with minimal cytotoxicity toward mammalian cells.

Highly pathogenic Gram-negative bacteria and their drug resistance are a severe public health threat with high mortality. Gram-negative bacteria are hard to kill due to the complex cell envelopes with low permeability and extra defense mechanisms. It is challenging to treat them with current strategies, mainly including antibiotics, peptides, polymers, and some hybrid materials, which still face the issue of drug resistance, limited antibacterial selectivity, and severe side effects. Together with precise bacteria targeting, synergistic therapeutic modalities, including physical membrane damage and photodynamic eradication, are promising to combat Gram-negative bacteria. Herein, pathogen-specific polymeric antimicrobials were formulated from amphiphilic block copolymers, poly(butyl methacrylate)-b-poly(2-(dimethylamino) ethyl methacrylate-co-eosin)-b-ubiquicidin, PBMA-b-P(DMAEMA-co-EoS)-UBI, in which pathogen-targeting peptide ubiquicidin (UBI) was tethered in the hydrophilic chain terminal, and Eosin-Y was copolymerized in the hydrophilic block. The micelles could selectively adhere to bacteria instead of mammalian cells, inserting into the bacteria membrane to induce physical membrane damage and out-diffusion of intracellular milieu. Furthermore, significant in situgeneration of reactive oxygen species was observed upon light irradiation, achieving further photodynamic eradication. Broad-spectrum bacterial inhibition was demonstrated for the polymeric antimicrobials, especially highly opportunistic Gram-negative bacteria, such as Pseudomona aeruginosa(P. aeruginosa) based on the synergy of physical destruction and photodynamic therapy, without detectable resistance. In vivo P. aeruginosa-infected knife injury model and burn model both proved good potency of bacteria eradication and promoted wound healing, which was comparable with commercial antibiotics, yet no risk of drug resistance. It is promising to hurdle the infection and resistance suffered from highly opportunistic bacteria.

Phototherapy has great application prospects in superficial tumors, such as melanoma, esophageal cancer, and breast carcinoma, owing to the advantages of noninvasiveness, high spatiotemporal selectivity, and less side effects. However, classical phototherapies including photodynamic and photothermal therapy still need to settle the bottleneck problems of poor efficacy, inevitable thermal damage, and a high rate of postoperative recurrence. In this study, we developed a nanocomposite with excellent optical properties and immune-stimulating properties, termed PBP@CpG, which was obtained by functionalizing black phosphorus (BP) with polydopamine and further adsorbing CpG. Benefiting from the protection of polydopamine against BP, ideal light absorption, and photoacoustic conversion properties, PBP@CpG not only enables precisely delineation of the tumor region with photoacoustic imaging but also powerfully disrupts the plasma membrane and cytoskeleton of tumor cells with a photoacoustic cavitation effect. In addition, we found that the photoacoustic cavitation effect was also capable of inducing immunogenic cell death and remarkably strengthening the antitumor immune response upon cooperating with immune adjuvant CpG. Therefore, PBP@CpG was expected to provide a promising nanoplatform for optical theranostics and herald a new strategy of photoimmunotherapy based on the photoacoustic cavitation effects and immunostimulatory effect.

Drilling-induced formation damage is the key factor dominating the failure of the development of hydrocarbon reservoirs with low-permeability (i.e., tight formation). In this paper, a new low-damage drilling fluid was formulated, evaluated, and applied to well-drilling operations in a sandstone oil reservoir with low-permeability in the Shengli Oilfield, China. To formulate this low-damage drilling fluid, filter-cake forming agents were used to prevent fluid loss, inhibitors were used to enhance the shale inhibition of the fluid, surfactants were used to minimize water block, and inorganic salts were used to enhance compatibility. A holistic experimental approach combining micro-computed tomography (CT), scanning electron microscopy (SEM), Fourier transform-infrared spectroscopy (FT-IR), and X-ray diffraction (XRD) techniques was designed to identify the underlying interactions between new and conventional drilling fluids and rock samples as well as the corresponding damage mechanisms, demonstrating the significant mitigation effects of the newly formulated drilling fluid on formation damage, which mainly results from the hydration of clay minerals and the invasion of solid particles. The newly formulated low-damage drilling fluid then extended its applications to well-drilling operations with excellent performance. Not only can the new low-damage drilling fluid avoid non-fracturing stimulation, but also reduce the drilling operational costs and time, minimize the formation damage, and facilitate extending the reservoir life for a longer time.