Surface charge switchable fluorinated small molecular micelles for enhanced photodynamic therapy for bacterial infections.

Photodynamic therapy (PDT) employs reactive oxygen species (ROS) from a photosensitizer (PS) under light, inhibiting multi-drug resistance in bacteria. However, hypoxic conditions in infection sites and biofilms challenge PDT efficiency. We developed fluorinated small molecular micelles (PF-CBMs) as PS carriers to address this, relieving hypoxia and enhancing PS penetration into biofilms. Perfluorocarbons in PF-CBMs transport more oxygen due to their excellent oxygen-dissolving capability. Fluorination enhances loading capacity and serum stability, reduces premature release, and improves cellular uptake, to improve PDT efficacy. PF-CBMs, with acid-induced surface charge transformation, exhibit superior biofilm penetration, resulting in increased antibiofilm activity of PDT. Compared to fluorine-free micelles (PC-CBMs), PF-CBMs demonstrate better serum stability, higher drug loading, and reduced premature release, leading to significantly improved antibacterial efficacy in vitro and in vivo. In conclusion, fluorinated micelles with surface charge reversal enhance PDT for antibacterial and antibiofilm applications.

Tumor microenvironment ameliorative and adaptive nanoparticles with photothermal-to-photodynamic switch for cancer phototherapy.

The notorious tumor microenvironment (TME) usually becomes more deteriorative during phototherapeutic progress that hampers the antitumor efficacy. To overcome this issue, we herein report the ameliorative and adaptive nanoparticles (TPASIC-PFH@PLGA NPs) that simultaneously reverse hypoxia TME and switch photoactivities from photothermal-dominated state to photodynamic-dominated state to maximize phototherapeutic effect. TPASIC-PFH@PLGA NPs are designed by incorporating oxygen-rich liquid perfluorohexane (PFH) into the intraparticle microenvironment to regulate the intramolecular motions of AIE photosensitizer TPASIC. TPASIC exhibits a unique aggregation-enhanced reactive oxygen species (ROS) generation feature. PFH incorporation affords TPASIC the initially dispersed state, thus promoting active intramolecular motions and photothermal conversion efficiency. While PFH volatilization leads to nanoparticle collapse and the formation of tight TPASIC aggregates with largely enhanced ROS generation efficiency. As a consequence, PFH incorporation not only currently promotes both photothermal and photodynamic efficacies of TPASIC and increases the intratumoral oxygen level, but also enables the smart photothermal-to-photodynamic switch to maximize the phototherapeutic performance. The integration of PFH and AIE photosensitizer eventually delivers more excellent antitumor effect over conventional phototherapeutic agents with fixed photothermal and photodynamic efficacies. This study proposes a new nanoengineering strategy to ameliorate TME and adapt the treatment modality to fit the changed TME for advanced antitumor applications.

Therapeutic utility of Perfluorocarbon Oxygent in limiting the severity of subarachnoid hemorrhage in mice.

Subarachnoid hemorrhage (SAH) is the deadliest form of hemorrhagic stroke; however, effective therapies are still lacking. Perfluorocarbons (PFCs) are lipid emulsion particles with great flexibility and their much smaller size as compared to red blood cells (RBCs) allows them to flow more efficiently within the blood circulation. Due to their ability to carry oxygen, a specific PFC-based emulsion, PFC-Oxygent, has been used as a blood substitute; however, its role in cerebral blood flow regulation is unknown. Adult C57BL/6 wildtype male mice were subjected to an endovascular perforation model of SAH followed by an intravenous (i.v.) injection of 9 ml/kg PFC-Oxygent or no treatment at 5 h after SAH. At 48 h after SAH, functional and anatomical outcomes were assessed. We found that SAH resulted in significant neurologic and motor deficits which were prevented by PFC-Oxygent treatment. We found that SAH-induced vasospasm, reduced RBC deformability, and augmented endothelial dysfunction were also restricted by PFC-Oxygent treatment. Moreover, mitochondrial activity and fusion proteins were also markedly decreased as assessed by oxidative phosphorylation (OXPHOS) after SAH. Interestingly, PFC-Oxygent treatment brought the mitochondrial activity close to the basal level. Moreover, SAH attenuated the level of phosphorylated AMP-activated protein kinase (pAMPK), whereas PFC treatment improved pAMPK levels. These data show the beneficial effects of PFC-Oxygent in limiting the severity of SAH. Further studies are needed to fully understand the mechanism through which PFC-Oxygent exerts its beneficial effects in limiting SAH severity.

Enhanced Fe(II)-artemisinin-mediated chemodynamic therapy with efficient Fe(III)/Fe(II) conversion circulation for cancer treatment.

Existing strategies to investigate the antitumor effects of artemisinin and its derivatives (ART) are inadequate. Both free Fe(II) and heme in mitochondria have been proposed to be ART activators. However, the two impact factors have been considered separately or have not been thoroughly investigated. Here, the designed ART-based novel nanosystem with transferrin-modified hollow mesoporous silica nanoparticles as drug-delivery carriers is loaded with a functional artemisinin derivative (Cou-DHA), glucose oxidase, and perfluoropentane inside the cavity, which can enhance synergistic Fe(II)-ART-mediated chemodynamic therapy (CDT). Under the action of H2O2 generated by starvation therapy, the Fenton reaction occurs with Fe(III) in transferrin converted into free Fe(II). Remarkably, this report is the first to provide Fe(II) to ART actively and efficiently by combining starvation therapy and Fenton reaction-based CDT. Importantly, mitochondria-targeted Cou-DHA delivers ART into the mitochondria to sensitize the anticancer effects of ART with the supplied Fe(II) to realize Fe(II)-ART-mediated CDT. The ART-based novel nanosystem developed in our work thus has great potential for exploitation in advanced cancer therapies.

TME-Responsive Nanoplatform with Glutathione Depletion for Enhanced Tumor-Specific Mild Photothermal/Gene/Ferroptosis Synergistic Therapy.

Background: Triple negative breast cancer (TNBC) is one of the worst prognosis types of breast cancer that urgently needs effective therapy methods. However, cancer is a complicated disease that usually requires multiple treatment modalities. Methods: A tumor microenvironment (TME)-responsive PFC/TRIM37@Fe-TA@HA (abbreviated as PTFTH) nanoplatform was constructed by coating Fe3+ and tannic acid (TA) on the surface of TRIM37-siRNA loaded phase-transition perfluorocarbon (PFC) nanodroplets and further modifying them with hyaluronic acid (HA) to achieve tumor-specific mild photothermal/gene/ferroptosis synergistic therapy (MPTT/GT/ Ferroptosis) in vitro. Once internalized into tumor cells through CD44 receptor-mediated active targeting, the HA shell of PTFTH would be preliminarily disassembled by hyaluronidase (HAase) to expose the Fe-TA metal-phenolic networks (MPNs), which would further degrade in response to an acidic lysosomal environment, leading to HAase/pH dual-responsive release of Fe3+ and PFC/TRIM37. Results: PTFTH showed good biocompatibility in vitro. On the one hand, the released Fe3+ could deplete the overexpressed glutathione (GSH) through redox reactions and produce Fe2+, which in turn converts endogenous H2O2 into highly cytotoxic hydroxyl radicals (•OH) for chemodynamic therapy (CDT). On the other hand, the local hyperthermia generated by PTFTH under 808 nm laser irradiation could not only improve CDT efficacy through accelerating the Fe2+-mediated Fenton reaction, but also enhance TRIM37-siRNA delivery for gene therapy (GT). The consumption of GSH and accumulation of •OH synergistically augmented intracellular oxidative stress, resulting in substantial tumor cell ferroptosis. Moreover, PTFTH possessed outstanding contrast enhanced ultrasound (CEUS), photoacoustic imaging (PAI) and magnetic resonance imaging (MRI) ability. Conclusion: This PTFTH based multiple-mode therapeutic strategy has successfully achieved a synergistic anticancer effect in vitro and has the potential to be translated into clinical application for tumor therapy in future.

Carcinomembrane-Camouflaged Perfluorochemical Dual-Layer Nanopolymersomes Bearing Indocyanine Green and Camptothecin Effectuate Targeting Photochemotherapy of Cancer.

Photochemotherapy has been recognized as a promising combinational modality for cancer treatment. However, difficulties such as off-target drug delivery, systemic toxicity, and the hypoxic nature of the tumor microenvironment remain hindrances to its application. To overcome these challenges, cancer cell membrane camouflaged perfluorooctyl bromide (PFOB) dual-layer nanopolymersomes bearing indocyanine green (ICG) and camptothecin (CPT), named MICFNS, were developed in this study, and melanoma was exploited as the model for MICFNS manufacture and therapeutic application. Our data showed that MICFNS were able to stabilize both ICG and CPT in the nanocarriers and can be quickly internalized by B16F10 cells due to melanoma membrane-mediated homology. Upon NIR irradiation, MICFNS can trigger hyperthermia and offer enhanced singlet oxygen production due to the incorporation of PFOB. With ≥10/2.5 µM ICG/CPT, MICFNS + NIR can provide comparable in vitro cancericidal effects to those caused by using an 8-fold higher dose of encapsulated CPT alone. Through the animal study, we further demonstrated that MICFNS can be quickly brought to tumors and have a longer retention time than those of free agents in vivo. Moreover, the MICFNS with 40/10 µM ICG/CPT in combination with 30 s NIR irradiation can successfully inhibit tumor growth without systemic toxicity in mice within the 14 day treatment. We speculate that such an antitumoral effect was achieved by phototherapy followed by chemotherapy, a two-stage tumoricidal process performed by MICFNS. Taken together, we anticipate that MICFNS, a photochemotherapeutic nanoplatform, has high potential for use in clinical anticancer treatment.

Sonodynamic and sonomechanical effect on cellular stemness and extracellular physicochemical environment to potentiate chemotherapy.

BACKGROUND: Hypoxia-activated prodrug (HAP) is a promising candidate for highly tumor-specific chemotherapy. However, the oxygenation heterogeneity and dense extracellular matrix (ECM) of tumor, as well as the potential resistance to chemotherapy, have severely impeded the resulting overall efficacy of HAP. RESULTS: A HAP potentiating strategy is proposed based on ultrasound responsive nanodroplets (PTP@PLGA), which is composed of protoporphyrin (PpIX), perfluoropropane (PFP) and a typical HAP, tirapazamine (TPZ). The intense vaporization of PFP upon ultrasound irradiation can magnify the sonomechanical effect, which loosens the ECM to promote the penetration of TPZ into the deep hypoxic region. Meanwhile, the PpIX enabled sonodynamic effect can further reduce the oxygen level, thus activating the TPZ in the relatively normoxic region as well. Surprisingly, abovementioned ultrasound effect also results in the downregulation of the stemness of cancer cells, which is highly associated with drug-refractoriness. CONCLUSIONS: This work manifests an ideal example of ultrasound-based nanotechnology for potentiating HAP and also reveals the potential acoustic effect of intervening cancer stem-like cells.

Synergistic Steatosis Induction in Mice: Exploring the Interactions and Underlying Mechanisms between PFOA and Tributyltin.

This study explores the impact of environmental pollutants on nuclear receptors (CAR, PXR, PPARα, PPARγ, FXR, and LXR) and their heterodimerization partner, the Retinoid X Receptor (RXR). Such interaction may contribute to the onset of non-alcoholic fatty liver disease (NAFLD), which is initially characterized by steatosis and potentially progresses to steatohepatitis and fibrosis. Epidemiological studies have linked NAFLD occurrence to the exposure to environmental contaminants like PFAS. This study aims to assess the simultaneous activation of nuclear receptors via perfluorooctanoic acid (PFOA) and RXR coactivation via Tributyltin (TBT), examining their combined effects on steatogenic mechanisms. Mice were exposed to PFOA (10 mg/kg/day), TBT (5 mg/kg/day) or a combination of them for three days. Mechanisms underlying hepatic steatosis were explored by measuring nuclear receptor target gene and lipid metabolism key gene expressions, by quantifying plasma lipids and hepatic damage markers. This study elucidated the involvement of the Liver X Receptor (LXR) in the combined effect on steatosis and highlighted the permissive nature of the LXR/RXR heterodimer. Antagonistic effects of TBT on the PFOA-induced activation of the Pregnane X Receptor (PXR) and Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) were also observed. Overall, this study revealed complex interactions between PFOA and TBT, shedding light on their combined impact on liver health.

Ultrasound-responsive gallium protoporphyrin and oxygen loaded perfluoropentane nanodroplets for effective sonodynamic therapy of implant infections.

Implant infections are severe complications in clinical treatment, which often accompany the formation of bacterial biofilms with high antibiotic resistance. Sonodynamic therapy (SDT) is an antibiotic-free method that can generate reactive oxygen species (ROS) to kill bacteria under ultrasound (US) treatment. However, the extracellular polymeric substances (EPS) barrier of bacterial biofilms and the hypoxic microenvironment significantly limit the antibiofilm activity of SDT. In this study, lipid-shelled perfluoropentane (PFP) nanodroplets loaded with gallium protoporphyrin IX (GaPPIX) and oxygen (O2) (LPGO NDs) were developed for the treatment of implant infections. Under US stimulation, LPGO NDs undergo the cavitation effect and disrupt the biofilm structure like bombs due to liquid-gas phase transition. Meanwhile, the LPGO NDs release O2 and GaPPIX upon US stimulation. The released O2 can alleviate the hypoxic microenvironment in the biofilm and enhance the ROS formation by GaPPIX for enhanced bacterial killing. In vivo experimental results demonstrate that the LPGO NDs can efficiently treat implant infections of methicillin-resistant Staphylococcus aureus (MRSA) in a mouse model by disrupting the biofilm structure, alleviating hypoxia, and enhancing bacterial killing by SDT. Therefore, this work provides a new multifunctional sonosensitizer to overcome the limitations of SDT for treating implant infections.

Chitosan-based multifunctional oxygenating antibiotic hydrogel dressings for managing chronic infection in diabetic wounds.

Current treatment strategies for infection of chronic wounds often result in compromised healing and necrosis due to antibiotic toxicity, and underlying biomarkers affected by treatments are not fully known. Here, a multifunctional dressing was developed leveraging the unique wound-healing properties of chitosan, a natural polysaccharide known for its numerous benefits in wound care. The dressing consists of an oxygenating perfluorocarbon functionalized methacrylic chitosan (MACF) hydrogel incorporated with antibacterial polyhexamethylene biguanide (PHMB). A non-healing diabetic infected wound model with emerging metabolomics tools was used to explore the anti-infective and wound healing properties of the resultant multifunctional dressing. Direct bacterial bioburden assessment demonstrated superior antibacterial properties of hydrogels over a commercial dressing. However, wound tissue quality analyses confirmed that sustained PHMB for 21 days resulted in tissue necrosis and disturbed healing. Therefore, a follow-up comparative study investigated the best treatment course for antiseptic application ranging from 7 to 21 days, followed by the oxygenating chitosan-based MACF treatment for the remainder of the 21 days. Bacterial counts, tissue assessments, and lipidomics studies showed that 14 days of application of MACF-PHMB dressings followed by 7 days of MACF dressings provides a promising treatment for managing infected non-healing diabetic skin ulcers.

Enhanced breast cancer treatment using phototherapy and RNS therapy with macrophage membrane-coated liposomes.

Breast cancer, the predominant malignancy afflicting women, continues to pose formidable challenges despite advancements in therapeutic interventions. This study elucidates the potential of phototherapy, comprising both photothermal and photodynamic therapy (PTT/PDT), as a novel and promising modality. To achieve this goal, we devised liposomes coated with macrophage cell membranes including macrophage-associated membrane proteins, which have demonstrated promise in biomimetic delivery systems for targeting tumors while preserving their inherent tumor-homing capabilities. This integrated biomimetic delivery system comprised IR780, NONOate, and perfluorocarbon. This strategic encapsulation aims to achieve a synergistic combination of photodynamic therapy (PDT) and reactive nitrogen species (RNS) therapy. Under near-infrared laser irradiation at 808 nm, IR780 demonstrates its ability to prolifically generate reactive oxygen species (ROS), including superoxide anion (O2•-), singlet oxygen, and hydroxyl radical (·OH). Simultaneously, NONOate releases nitric oxide (NO) gas upon the same laser irradiation, thereby engaging with IR780-induced ROS to facilitate the formation of peroxynitrite anion (ONOO-), ultimately inducing programmed cell death in cancer cells. Additionally, the perfluorocarbon component of our delivery system exhibits a notable affinity for oxygen and demonstrates efficient oxygen-carrying capabilities. Our results demonstrate that IR780-NO-PFH-Lip@M significantly enhances breast cancer cell toxicity, reducing proliferation and in vivo tumor growth through simultaneous heat, ROS, and RNS production. This study contributes valuable insights to the ongoing discourse on innovative strategies for advancing cancer therapeutics.

Vaporization of perfluorocarbon attenuates sea-water-drowning-induced acute lung injury by deactivating the NLRP3 inflammasomes in canines.

Seawater-drowning-induced acute lung injury (SD-ALI) is a life-threatening disorder characterized by increased alveolar-capillary permeability, an excessive inflammatory response, and refractory hypoxemia. Perfluorocarbons (PFCs) are biocompatible compounds that are chemically and biologically inert and lack toxicity as oxygen carriers, which could reduce lung injury in vitro and in vivo. The aim of our study was to explore whether the vaporization of PFCs could reduce the severity of SD-ALI in canines and investigate the underlying mechanisms. Eighteen beagle dogs were randomly divided into three groups: the seawater drowning (SW), perfluorocarbon (PFC), and control groups. The dogs in the SW group were intratracheally administered seawater to establish the animal model. The dogs in the PFC group were treated with vaporized PFCs. Probe-based confocal laser endomicroscopy (pCLE) was performed at 3 h. The blood gas, volume air index (VAI), pathological changes, and wet-to-dry (W/D) lung tissue ratios were assessed. The expression of heme oxygenase-1 (HO-1), nuclear respiratory factor-1 (NRF1), and NOD-like receptor family pyrin domain containing-3 (NLRP3) inflammasomes was determined by means of quantitative real-time polymerase chain reaction (qRT-PCR) and immunological histological chemistry. The SW group showed higher lung injury scores and W/D ratios, and lower VAI compared to the control group, and treatment with PFCs could reverse the change of lung injury score, W/D ratio and VAI. PFCs deactivated NLRP3 inflammasomes and reduced the release of caspase-1, interleukin-1ß (IL-1ß), and interleukin-18 (IL-18) by enhancing the expression of HO-1 and NRF1. Our results suggest that the vaporization of PFCs could attenuate SD-ALI by deactivating NLRP3 inflammasomes via the HO-1/NRF1 pathway.

Endowing Pt(IV) with Perfluorocarbon Chains and Human Serum Albumin Encapsulation for Highly Effective Antitumor Chemoimmunotherapy.

Tumor metastases and reoccurrence are considered the leading causes of cancer-associated deaths. As an emerging therapeutic method, increasing research efforts have been devoted to immunogenic cell death (ICD)-inducing compounds to solve the challenge. The clinically approved chemotherapeutic Pt complexes are not or are only poorly able to trigger ICD. Herein, the axial functionalization of the Pt(II) complex cisplatin with perfluorocarbon chains into ICD-inducing Pt(IV) prodrugs is reported. Strikingly, while the Pt(II) complex as well as the perfluorocarbon ligands did not induce ICD, the Pt(IV) prodrug demonstrated unexpectantly the induction of ICD through accumulation in the endoplasmic reticulum and generation of reactive oxygen species in this organelle. To enhance the pharmacological properties, the compound was encapsulated with human serum albumin into nanoparticles. While selectively accumulating in the tumorous tissue, the nanoparticles demonstrated a strong tumor growth inhibitory effect against osteosarcoma inside a mouse model. In vivo tumor vaccine analysis also demonstrated the ability of Pt(IV) to be an ideal ICD inducer. Overall, this study reports on axially perfluorocarbon chain-modified Pt(IV) complexes for ICD induction and chemoimmunotherapy in osteosarcoma.

Platelet membrane encapsulated curcumin nanomaterial-mediated specific thrombolysis and anti-thrombotic treatment among pregnant women.

The current treatment for venous thrombosis during pregnancy is ineffective, primarily, due to the unique physiology of pregnant women. Most clinical medications have fetal side effects when they circulate in the body. We first synthesized nanomaterials (Cur-PFP@PC) using poly lactic-co-glycolic acid (PLGA) as the base material, with curcumin (Cur) and perfluoropentane (PFP) as core components. Subsequently, we encapsulated Cur-PFP@PC into the platelet membrane to synthesize P-Cur-PFP@PC. Under ultrasound guidance, in combination with low-intensity focused ultrasound (LIFU), PFP underwent a phase change, resulting in thrombolysis. The generated microbubbles enhanced the signal impact of ultrasound, and P-Cur-PFP@PC showed better performance than Cur-PFP@PC. P-Cur-PFP@PC can target thrombosis treatment, achieve visually and precisely controlled drug release, and repair damaged blood vessels, thus avoiding the adverse effects associated with traditional long-term drug administration.

The therapeutic potential of isosakuranetin against perfluorooctane sulfonate instigated cardiac toxicity via modulating Nrf-2/Keap-1 pathway, inflammatory, apoptotic, and histological profile.

Perfluorooctane sulfonate (PFOS) is a pervasive organic toxicant that damages body organs, including heart. Isosakuranetin (ISN) is a plant-based flavonoid that exhibits a broad range of pharmacological potentials. The current investigation was conducted to evaluate the potential role of ISN to counteract PFOS-induced cardiac damage in rats. Twenty-four albino rats (Rattus norvegicus) were distributed into four groups, including control, PFOS (10 mg/kg) intoxicated, PFOS + ISN (10 mg/kg + 20 mg/kg) treated, and ISN (20 mg/kg) alone supplemented group. It was revealed that PFOS intoxication reduced the expressions of Nrf-2 and its antioxidant genes while escalating the expression of Keap-1. Furthermore, PFOS exposure reduced the activities of glutathione reductase (GSR), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), Heme oxygenase-1 (HO-1) and glutathione (GSH) contents while upregulating the levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Besides, PFOS administration upregulated the levels of creatine kinase-MB (CK-MB), troponin I, creatine phosphokinase (CPK), and lactate dehydrogenase (LDH). Moreover, the levels of tumor necrosis factor-alpha (TNF-α), nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) were increased after PFOS intoxication. Additionally, PFOS exposure downregulated the expression of Bcl-2 while upregulating the expressions of Bax and Caspase-3. Furthermore, PFOS administration disrupted the normal architecture of cardiac tissues. Nonetheless, ISN treatment remarkably protected the cardiac tissues via regulating aforementioned dysregulations owing to its antioxidative, anti-inflammatory, and antiapoptotic properties.

CD133-targeted multifunctional nanomicelles for dual-modality imaging and synergistic high-intensity focus ultrasound (HIFU) ablation on pancreatic cancer in nude mice.

Pancreatic cancer is an aggressive and highly fatal malignant tumor. Recent studies have shown that cancer stem cells (CSCs) play an important role in resisting current therapeutic modalities. Furthermore, CD133 is highly expressed in CSCs. High-intensity focused ultrasound (HIFU) is a promising non-invasive therapeutic strategy for unresectable pancreatic cancers. In our study, we synthesized targeted CD133 organosilane nanomicelles by encapsulating perfluorohexane (PFH). The CD133 antibody on the surface could specifically bind to CD133-positive pancreatic cancer cells and selectively concentrate in pancreatic cancer tumor tissues. PFH was introduced to improve the ablation effect of HIFU due to its liquid-gas phase transition properties. By combining with the dorsal skinfold window chamber model (DSWC) of pancreatic cancer in nude mice, multiphoton fluorescence microscopy was used to evaluate the targeting effect of nanomicelles on pancreatic cancer tumor tissue. These multifunctional nanomicelles synergistically affected HIFU treatment of pancreatic cancer, providing an integrated research platform for diagnosing and treating pancreatic cancer with HIFU.

Gold Nanorod-Loaded Nano-Contrast Agent with Composite Shell-Core Structure for Ultrasonic/Photothermal Imaging-Guided Therapy in Ischemic Muscle Disorders.

Purpose: This study aims to broaden the application of nano-contrast agents (NCAs) within the realm of the musculoskeletal system. It aims to introduce novel methods, strategies, and insights for the clinical management of ischemic muscle disorders, encompassing diagnosis, monitoring, evaluation, and therapeutic intervention. Methods: We developed a composite encapsulation technique employing O-carboxymethyl chitosan (OCMC) and liposome to encapsulate NCA-containing gold nanorods (GNRs) and perfluoropentane (PFP). This nanoscale contrast agent was thoroughly characterized for its basic physicochemical properties and performance. Its capabilities for in vivo and in vitro ultrasound imaging and photothermal imaging were authenticated, alongside a comprehensive biocompatibility assessment to ascertain its effects on microcirculatory perfusion in skeletal muscle using a murine model of hindlimb ischemia, and its potential to augment blood flow and facilitate recovery. Results: The engineered GNR@OCMC-liposome/PFP nanostructure exhibited an average size of 203.18±1.49 nm, characterized by size uniformity, regular morphology, and a good biocompatibility profile. In vitro assessments revealed NCA's potent photothermal response and its transformation into microbubbles (MBs) under near-infrared (NIR) irradiation, thereby enhancing ultrasonographic visibility. Animal studies demonstrated the nanostructure's efficacy in photothermal imaging at ischemic loci in mouse hindlimbs, where NIR irradiation induced rapid temperature increases and significantly increased blood circulation. Conclusion: The dual-modal ultrasound/photothermal NCA, encapsulating GNR and PFP within a composite shell-core architecture, was synthesized successfully. It demonstrated exceptional stability, biocompatibility, and phase transition efficiency. Importantly, it facilitates the encapsulation of PFP, enabling both enhanced ultrasound imaging and photothermal imaging following NIR light exposure. This advancement provides a critical step towards the integrated diagnosis and treatment of ischemic muscle diseases, signifying a pivotal development in nanomedicine for musculoskeletal therapeutics.

Carbon-chain length determines the binding affinity and inhibitory strength of per- and polyfluoroalkyl substances on human and rat steroid 5α-reductase 1 activity.

Per- and polyfluoroalkyl substances (PFAS) are widely used synthetic chemicals that persist in the environment and bioaccumulate in animals and humans. There is growing evidence that PFAS exposure adversely impacts neurodevelopment and neurological health. Steroid 5α-reductase 1 (SRD5A1) plays a key role in neurosteroidogenesis by catalyzing the conversion of testosterone or pregnenolone to neuroactive steroids, which influence neural development, cognition, mood, and behavior. This study investigated the inhibitory strength and binding interactions of 18 PFAS on human and rat SRD5A1 activity using enzyme assays, molecular docking, and structure-activity relationship analysis. Results revealed that C9-C14 PFAS carboxylic acid at 100 µM significantly inhibited human SRD5A1, with IC50 values ranged from 10.99 µM (C11) to 105.01 µM (C14), and only one PFAS sulfonic acid (C8S) significantly inhibited human SRD5A1 activity, with IC50 value of 8.15 µM. For rat SRD5A1, C9-C14 PFAS inhibited rat SRD5A1, showing the similar trend, depending on carbon number of the carbon chain. PFAS inhibit human and rat SRD5A1 in a carbon chain length-dependent manner, with optimal inhibition around C11. Kinetic studies indicated PFAS acted through mixed inhibition. Molecular docking revealed PFAS bind to the domain between NADPH and testosterone binding site of both SRD5A1 enzymes. Inhibitory potency correlated with physicochemical properties like carbon number of the carbon chain. These findings suggest PFAS may disrupt neurosteroid synthesis and provide insight into structure-based inhibition of SRD5A1.

Hemostatic and Ultrasound-Controlled Bactericidal Silk Fibroin Hydrogel via Integrating a Perfluorocarbon Nanoemulsion.

Excessive blood loss and infections are the prominent risks accounting for mortality and disability associated with acute wounds. Consequently, wound dressings should encompass adequate adhesive, hemostatic, and bactericidal attributes, yet their development remains challenging. This investigation presented the benefits of incorporating a perfluorocarbon nanoemulsion (PPP NE) into a silk-fibroin (SF)-based hydrogel. By stimulating the ß-sheet conformation of the SF chains, PPP NEs drastically shortened the gelation time while augmenting the elasticity, mechanical stability, and viscosity of the hydrogel. Furthermore, the integration of PPP NEs improved hemostatic competence by boosting the affinity between cells and biomacromolecules. It also endowed the hydrogel with ultrasound-controlled bactericidal ability through the inducement of inner cavitation by perfluorocarbon and reactive oxygen species (ROS) generated by the sonosensitizer protoporphyrin. Ultimately, we employed a laparotomy bleeding model and a Staphylococcus aureus-infected trauma wound to demonstrate the first-aid efficacy. Thus, our research suggested an emulsion-incorporating strategy for managing emergency wounds.

Tumor-Targeted Perfluorinated Micelles as Efficient Theranostic Agents Combining Positron Emission Tomography and Radiosensitization.

We report the synthesis of biocompatible perfluorinated micelles designed to improve radiotherapeutic efficacy in a radioresistant tumor environment. In vitro and in vivo behaviors of perfluorinated micelles were assessed at both cellular and tissular levels. The micellar platform offers key advantages as theranostic tool: (i) small size, allowing deep tissue penetration; (ii) oxygen transport to hypoxic tissues; (iii) negligible toxicity in the absence of ionizing radiation; (iv) internalization into cancer cells; (v) potent radiosensitizing effect; and (vi) excellent tumor-targeting properties, as monitored by positron emission tomography. We have demonstrated strong in vitro radiosensitizing effects of the micelle and in vivo tumor targeting, making this nanometric carrier a promising tool for the potentiation of focused radiotherapy.