Reactive oxygen species (ROS) provide a promising way to fight bacterial infection and meet the persistent challenge of antibiotic resistance. Nanoenzyme mimics natural enzyme and becomes an effective regulator of ROS level. In this study, NH2-MIL-88B with high specific surface area was selected as the core, and the covalent organic skeleton material TP-TA COF was wrapped by \"sequential growth\" technology. Subsequently, through the second hydrothermal treatment, the inorganic material CuS with excellent photothermal performance was integrated into the outer layer, and the NH2-MIL-88B@TP-TA@CuSX composite nanoenzyme was synthesized. Different from the traditional nano-enzyme, NH2-MIL-88B@TP-TA@CuSX nano-enzyme still has good catalytic effect under neutral conditions (pH=7). In addition, NH2-MIL-88B@TP-TA@CuSX has good near infrared (NIR) absorption rate and high photothermal conversion efficiency (PTCE is 48.7 %), which can be used for photothermal treatment (PTT) of bacteria. Mild photothermal effect can further enhance the enzyme-like catalytic activity of NH2-MIL-88B@TP-TA@CuSX, so that H2O2 can be more efficiently catalyzed to produce a large number of ROS. The experimental results in vitro show that NH2-MIL-88B@TP-TA@CuSX can effectively kill Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) in the presence of laser irradiation and H2O2.

Circulating tumor cell (CTC) in the blood is the main cause of cancer metastasis for death in cancer patients. It is extremely important for cancer diagnosis at an early stage and treatment to simultaneously detect and kill the CTCs. In this work, a new hybridized nanolayer, namely gold nanoparticle/gold nanorods@ Polydopamine (AuNPs/AuNRs@PDA), was coated on the Ω-shaped fiber optics (Ω-FO) for localized surface plasmonic resonance (LSPR) to perform tumor cell sensing and photothermal treatment (PTT). The PDA nanolayer was formed on a bare fiber optic through the self-polymerization of dopamine under mild conditions. The AuNRs and AuNPs were absorbed on the surface of the PDA nanolayer to form a hybridized nanolayer. The hybridized nanolayer-modified Ω-FO LSPR exhibited a high refractive index sensitivity (RIS) of 37.59 (a.u/RIU) and photothermal conversion efficiency. After being modified with the recognition element of aptamer, the Ω-FO LSPR was used to develop a sensitive and specifical tumor cell sensing. Under the irradiation of near-infrared light (NIR) laser, the Ω-FO LSPR can kill the captured tumor cells with the apoptotic/necrotic rate of 62.6 % and low side-effect for the nontarget cells. The FO LSPR sensor realized the dual functions of CTC sensing and PTT, which provided a new idea for the early diagnosis and treatment of cancer.

The treatment of tumors still faces considerable challenges. While conventional treatments such as surgery, chemotherapy, and radiation therapy provide some curative effects, their side effects and limitations highlight the importance of finding more precise treatment strategies. Aptamers have become an important target molecule in the field of drug delivery systems due to their good affinity and targeting, and they have gradually become an important link from basic research to clinical application. In this paper, we discussed the latest progress of aptamer-mediated nanodrugs, as well as aptamer-mediated photodynamic therapy, photothermal therapy, and immunotherapy strategies for tumor treatment, and explored the possibility of aptamer-mediated therapy for accurate tumor treatment. The purpose of this review is to provide novel insights for treating tumors with aptamer-mediated therapies by summarizing these innovative strategies, thereby ultimately enhancing the therapeutic efficacy for cancer patients.

Tumor recurrence and massive bone defects are two critical challenges for postoperative treatment of oral and maxillofacial tumor, posing serious threats to the health of patients. Herein, in order to eliminate residual tumor cells and promote osteogenesis simultaneously, the hydrogen peroxide (H2O2) self-sufficient TCP-PDA-CaO2-CeO2 (TPCC) scaffolds are designed by preparing CaO2 or/and CeO2 nanoparticles (NPs)/chitosan solution and modifying the NPs into polydopamine (PDA)-modified 3D printed TCP scaffolds by rotary coating method. CaO2 NPs loaded on the scaffolds can release Ca2+ and sufficient H2O2 in the acidic tumor microenvironment (TME). The generated H2O2 can further produce hydroxyl radicals (·OH) under catalysis effect by peroxidase (POD) activity of CeO2 NPs, in which the photothermal effect of the PDA coating enhances its POD catalytic effect. Overall, NPs loaded on the scaffold chemically achieve a cascade reaction of H2O2 self-sufficiency and ·OH production, while functionally achieving synergistic effects on anti-tumor and bone promotion. In vitro and in vivo studies show that the scaffolds exhibit effective osteo-inductivity, induced osteoblast differentiation and promote osseointegration. Therefore, the multifunctional composite scaffolds not only validate the concept of chemo-dynamic therapy (CDT) cascade therapy, but also provide a promising clinical strategy for postoperative treatment of oral and maxillofacial tumor.

Uveal melanoma (UM) is an ocular cancer predominantly affecting adults, characterized by challenging diagnostic outcomes. This research endeavors to develop an innovative multifunctional nanocomposite system sensitive to near-infrared (NIR) radiation, serving as both a non-oxygen free-radical generator and a photothermal agent. The designed system combines azobis isobutyl imidazoline hydrochloride (AIBI) with mesoporous copper sulfide (MCuS) nanoparticles. MCuS harnesses NIR laser energy to induce photothermal therapy, converting light energy into heat to destroy cancer cells. Simultaneously, AIBI is activated by the NIR laser to produce alkyl radicals, which induce DNA damage in remaining cancer cells. This distinctive feature equips the designed system to selectively eliminate cancers in the hypoxic tumor microenvironment. MCuS is also beneficial to scavenge the overexpressed glutathione (GSH) in the tumor microenvironment. GSH generally consumes free radicals and hiders the PDT effect. To enhance control over AIBI release in cancer cells, 1-tetradecyl alcohol (TD), a phase-changing material, is introduced onto the surface of MCuS nanoparticles to create the final AMPT nanoparticle system. In vitro and in vivo experiments confirm the remarkable anti-tumor efficacy of AMPT. Notably, the study introduces an orthotopic tumor model for UM, demonstrating the feasibility of precise and effective targeted treatment within the ocular system.

The growing interest in graphene oxide (GO) for different biomedical applications requires thoroughly examining its safety. Therefore, there is an urgent need for reliable data on how GO nanoparticles affect healthy cells and organs. In the current work, we adopted a comprehensive approach to assess the influence of GO and its polyethylene glycol-modified form (GO-PEG) under near-infrared (NIR) exposure on several biological aspects. We evaluated the contractility of isolated frog hearts, the activity of two rat liver enzymes-mitochondrial ATPase and diamine oxidase (DAO), and the production of reactive oxygen species (ROS) in C2C12 skeletal muscle cells following direct exposure to GO nanoparticles. The aim was to study the influence of GO nanoparticles at multiple levels-organ; cellular; and subcellular-to provide a broader understanding of their effects. Our data demonstrated that GO and GO-PEG negatively affect heart contractility in frogs, inducing stronger arrhythmic contractions. They increased ROS production in C2C12 myoblasts, whose effects diminished after NIR irradiation. Both nanoparticles in the rat liver significantly stimulated DAO activity, with amplification of this effect after NIR irradiation. GO did not uncouple intact rat liver mitochondria but caused a concentration-dependent decline in ATPase activity in freeze/thaw mitochondria. This multifaceted investigation provides crucial insights into GOs potential for diverse implications in biological systems.

Polydopamine (PDA) as a melanin-like biomimetic material with excellent biocompatibility, full spectrum light absorption capacity and antioxidation property has been extensively applied in the biomedical field. Based on the high reactivity of dopamine (DA), exploiting new strategies to fabricate novel PDA-based nano-biomaterials with controllable size and improved performance is valuable and desirable. Herein, we reported a facile way to synthesize pyrrole-doped polydopamine-pyrrole nanoparticles (PDA-nPY NPs) with tunable size and enhanced near-infrared (NIR) absorption capacity through self-oxidative polymerization of DA with PY in an alkaline ethanol/H2O/NH4OH solution. The PDA-nPY NPs maintain excellent biocompatibility and surface reactivity as PDA. By regulating the volume of added PY, PDA-150PY NPs with a smaller size (<100 nm) and four-fold higher absorption intensity at 808 nm than that of PDA can be successfully fabricated. In vitro and in vivo experiments effectively further demonstrate that PDA-150PY NPs can effectively inhibit tumor growth and completely thermally ablate a tumor. It is believed that these PY doped PDA-nPY NPs can be a potential photothermal (PT) agent in biomedical application.

A new generation of nanoscale photosensitizer agents has improved photothermal capabilities, which has increased the impact of photothermal treatments (PTTs) in cancer therapy. Gold nanostars (GNS) are promising for more efficient and less invasive PTTs than gold nanoparticles. However, the combination of GNS and visible pulsed lasers remains unexplored. This article reports the use of a 532 nm nanosecond pulse laser and polyvinylpyrrolidone (PVP)-capped GNS to kill cancer cells with location-specific exposure. Biocompatible GNS were synthesized via a simple method and were characterized under FESEM, UV-visible spectroscopy, XRD analysis, and particle size analysis. GNS were incubated over a layer of cancer cells that were grown in a glass Petri dish. A nanosecond pulsed laser was irradiated on the cell layer, and cell death was verified via propidium iodide (PI) staining. We assessed the effectiveness of single-pulse spot irradiation and multiple-pulse laser scanning irradiation in inducing cell death. Since the site of cell killing can be accurately chosen with a nanosecond pulse laser, this technique will help minimize damage to the cells around the target cells.

Photodynamic therapy (PDT) induces immunogenic cell death (ICD) by producing reactive oxygen species (ROS), making it an ideal method for cancer treatment. However, the extremely lower level of oxygen, short half-life of produced ROS, and limited photosensitizers accumulating in the tumor site via intravenous administration are the main reasons that limit the further application of PDT. To address these issues, we loaded the photosensitizer porphine (THPP) into biomimetic gold nanorod-mesoporous silica core-shell nanoparticles (Au-MSN NPs) to prepare Au@MSN/THPP@CM NPs. We then seeded the NPs together with catalase (CAT) into a gelatin methacryloyl (GelMA) microgel matrix to form Au@MSN-Ter/THPP@CM@GelMA/CAT microspheres consisting of biomimetic nano@microgel. The NPs and biomimetic nano@microgel exhibited enhanced photodynamic (PD) reaction and excellent photothermal conversion ability. Moreover, we further conjugated an endoplasmic reticulum (ER) targeting ligand Tosyl Ethylenediamine (Ter) on the surface of Au-MSN NPs. The results showed that both Au@MSN-Ter/THPP@CM NPs and the finally formed Au@MSN-Ter/THPP@CM@GelMA/CAT biomimetic nano@microgel induced precise and prolonged ER stress through photodynamic reactions, which stimulated the exposure of the proapoptotic calreticulin (CRT) on the cell membrane and increased the release of high mobility group box 1 (HMGB1) form the nucleus in SKOV3 cells under near-infrared (NIR) laser irradiation. Additionally, a single dose of the nano@microgel delivered through minimally invasive injection generated a significant anti-tumor effect in the SKOV3 cell line-derived orthotopic ovarian cancer mouse model through a PD and PT combination therapy. This study offers a new strategy for enhanced PDT and provides a PD/PT synergistic treatment method for ovarian cancer.

Prosthetic joint infection (PJI) is a devastating complication requiring surgical intervention and prolonged antimicrobial treatment. The prevalence of PJI is on the rise, with an average incidence of 60,000 cases per year and a projected annual cost of $1.85 billion in the US. The underlying pathogenesis of PJI involves the formation of bacterial biofilms that protect the pathogen from the host immune response and antibiotics, making it difficult to eradicate such infections. Biofilms on implants are also resistant to mechanical brushing/scrubbing methods of removal. Since the removal of biofilms is currently only achievable by the replacement of the prosthesis, therapies aimed at eradicating biofilms while enabling retention of implants will revolutionize the management of PJIs. To address severe complications associated with biofilm-related infections on implants, we have developed a combination treatment that is based on a hydrogel nanocomposite system, containing d-amino acids (d-AAs) and gold nanorods, which can be delivered and transforms from a solution to a gel state at physiological temperature for sustained release of d-AAs and light-activated thermal treatment of infected sites. Using this two-step approach to utilize a near-infrared light-activated hydrogel nanocomposite system for thermal treatment, following initial disruption with d-AAs, we were able to successfully demonstrate in vitro the total eradication of mature Staphylococcus aureus biofilms grown on three-dimensional printed Ti-6Al-4V alloy implants. Using a combination of cell assays, computer-aided scanning electron microscopy analyses, and confocal microscopy imaging of the biofilm matrix, we could show 100% eradication of the biofilms using our combination treatment. In contrast, we were only able to see 25% eradication of the biofilms using the debridement, antibiotics, and implant retention method. Moreover, our hydrogel nanocomposite-based treatment approach is adaptable in the clinical setting and capable of combating chronic infections brought about by biofilms on medical implants.