F127 Micelles Research Articles

Hydroxypropyl Cellulose Hydrogel Containing Origanum vulgare ssp. hirtum Essential-Oil-Loaded Polymeric Micelles for Enhanced Treatment of Melanoma.

Origanum vulgare ssp. hirtum essential oil (OEO) is a natural oil with high therapeutic potential. For some applications, however, the development of novel formulations is still needed to improve the bioavailability and stability of OEO. In this study, we describe the fabrication of an original nanocomposite hydroxypropyl cellulose (HPC) physical hydrogel, containing OEO-loaded polymeric micelles, for topical delivery. The concentration of the main active compounds of OEO-carvacol and thymol-was determined using gas chromatography (GC) analysis. OEO was first encapsulated into Pluronic F127 micelles, and then embedded into HPC gel. Micellar and gel formulations of pure polymers and OEO-containing systems were characterized by dynamic light scattering (DLS) and rheology measurements, respectively. Selected formulations were evaluated for cytotoxicity and antiproliferative activity. The hydrogel formulation of HPC with micellar OEO (8% HPC, 2% F127, 1% OEO) exhibited sustained release of the oil and selectivity towards SH-4 tumor cells (an in vitro model of melanoma).

High efficacy of chloroquine-derived bile salts in Pluronic F127 micelles against blood-stage Plasmodium falciparum

Colloidal nanocarriers can play a key role in the efficacious delivery of drugs, including antimalarials. Here, we investigated the ability of polymeric micelles of the block copolymer F127 to act as nanovehicles for two organic salts derived from chloroquine and human bile acids, namely, chloroquinium cholate (iCQP1) and chloroquinium glycocholate (iCQP1g). We have previously reported the strong in vitro antiplasmodial activity of these salts, which displayed IC50 values of 13 and 15 nM against blood forms of Plasmodium falciparum, respectively. By deriving from amphiphilic lipids, iCQP1 and iCQP1g also enclose the ability to act as surface-active ionic liquids (SAILs). The micellization properties of neat F127 and of the F127/SAIL mixtures were initially investigated to gain physicochemical insight into the interaction between polymer and bioactive SAILs, resorting to differential scanning calorimetry, surface tension measurements and dynamic light scattering. Micelle formation by F127 is an endothermic process strongly temperature and concentration dependent. Interestingly, this process is significantly changed when the molar fraction of SAIL (xSAIL) in the F127/SAIL mixture is varied between 0.33 and 0.90. Both SAILs favor the formation of mixed micelles by decreasing the micellization temperature, and (observed only when for xSAIL = 0.33) by synergistically decreasing the cmc. Concomitantly, the micellar size is reduced from 18 to 13 nm as xSAIL is increased from 0.33 to 0.90. Crucially, in vitro assays show that when the SAILs are loaded into F127 polymeric micelles, their antiplasmodial efficacy is substantially enhanced, with a significant drop in IC50, especially for the iCQP1/F127 system. This opens new possibilities for the nanoformulations of antimalarial compounds.

Photophysical properties of lumichrome in aqueous solution tri-block copolymers

We have reported the photophysics of lumichrome (LUM)) in tri-block copolymers micelles of F-127 and P-123, having differences in length of hydrophilic unit. Due to the amphiphilic nature of polymeric micelles, and hydrophilic corona region, we observed the existence of different forms of LUM. We observed an extra emission peak of LUM at ∼ 430 nm and less percentage of existence of the A10 anionic form of LUM in case F-127. From time resolved anisotropy measurement, we have found that the LUM in F-127 micelle faced a more restricted environment than P-123 micelle.

A bioactive xyloglucan polysaccharide hydrogel mechanically enhanced by Pluronic F127 micelles for promoting chronic wound healing

Chronic wounds represent a formidable global healthcare challenge due to the bacteria infections and uncontrollable inflammation responses, while developing wound healing materials capable of resolving these issues remains a challenge. In this study, we integrated xyloglucan (XG) with Pluronic F127 diacrylate (F127DA)to develop a composite hydrogel for wound healing, where the XG introduced anti-inflammation and anti-bacterial properties to the construct, and F127DA provides the photocurable properties essential for hydrogel formation and robust mechanical characteristics to achieve physical strength that matches tissue regeneration. The material characterizations suggested that XG/F127DA hydrogels had great biostability, blood compatibility and antibacterial effects, which was suitable to be used as a wound healing material. The in vitro analysis by culturing L929 fibroblasts on the hydrogel surface demonstrated that the inclusion of XG could promote the cellular proliferation rate, migration rate, and re-epithelialization-related marker expression, while downregulate the inflammation process. The XG/F127DA hydrogel was further used for the full-thickness skin wound healing test on mice, where the inclusion of XG significantly increased the wound closure rate through reducing the inflammation responses, and promote re-epithelialization and angiogenesis. These results indicated that XG/F127DA hydrogel has great potential to be used for wound healing in future clinical translation.

Facile Preparation of Multifunctional Hydrogels with Sustained Resveratrol Release Ability for Bone Tissue Regeneration.

Injectable hydrogels show great promise for bone tissue engineering applications due to their high biocompatibility and drug delivery capabilities. The bone defects in osteoporosis are usually characterized by an oxidative and inflammatory microenvironment that impairs the regeneration capability of bone tissues. To attenuate the reactive oxygen species (ROS) and promote bone regeneration, an anti-oxidative hydrogel with osteogenic capacity was developed in this study. The poorly water soluble, natural antioxidant, resveratrol, was encapsulated in thiolated Pluronic F-127 micelles with over 50-times-enhanced solubility. The injectable hydrogel was facilely formed because of the new thioester bond between the free thiol group in modified F-127 and the arylate group in hyaluronic acid (HA)-acrylate. The resveratrol-loaded hydrogel showed good viscoelastic properties and in vitro stability and was cyto-compatible with bone-marrow-derived mesenchymal stem cells (BMSCs). The hydrogel allowed for a sustained release of resveratrol for at least two weeks and effectively enhanced the osteogenic differentiation of BMSCs by the up-regulation of osteogenic markers, including ALP, OCN, RUNX-2, and COL1. Moreover, the hydrogel exhibited anti-oxidative and anti-inflammatory abilities through the scavenging of intracellular ROS in RAW264.7 cells and inhibiting the gene expression and secretion of pro-inflammatory cytokines TNF-α and IL-1β under LPS exposure. In summary, the results suggest that our multifunctional hydrogel loaded with resveratrol bearing osteogenic, anti-oxidative, and anti-inflammatory actions is easily prepared and represents a promising resveratrol delivery platform for the repair of osteoporotic bone defects.

How Polyoxometalate Promote the Aggregation of a Cyanine Dye in the Aqueous Solution of Non-Ionic Copolymers of Varying Hydrophilic-Lipophilic Balance?

The nonradiative pathway leading to the photoisomerization of a cyanine dye is well-established information. However, the modulations induced in the photoisomerization pathway by a Keggin-type polyoxometalate in a confined media is new. Our study reveals that, in the presence of pluronic block copolymers F-108 and P-123, phosphomolybdic acid hydrate (PMA) promotes the aggregation of 3,3'-diethylthiadicarbocyanine iodide (DTDCI). The absorption spectra show a clear indication of a red-shifted trimer band in F-108 and P-123, whereas it is absent in F-127 and P-84. Fluorescence emission studies suggest that, in the presence of PMA, the rate of photoisomerization is accelerated in F-108, P-123, and P-84 micelles, whereas it is retarded in F-127 micelles. Time-resolved studies in the presence of PMA indicate the preference of F-108, P-84, and P-123 toward the trapped conformer of DTDCI, whereas F-127 favors the formation of photoisomer of DTDCI. Our findings imply the importance of the interplay between the hydrophobic and electrostatic interactions between the DTDCI cations and the PMA anions in nonionic micelles of varying hydrophilic-lipophilic balance (HLB). Dynamic light scattering (DLS) data suggest a modulation by PMA in the intermicellar electrostatic repulsions of a hydrophilic copolymer micelle, whereas its unaffected in a hydrophobic copolymeric micelle.

Integrin receptor-targeted, doxorubicin-loaded cerium oxide nanoparticles delivery to combat glioblastoma.

Aim: To assess the chemo-immunomodulatory effects of doxorubicin-loaded cerium oxide nanoparticles coated with oleyl amine-linked cyclic RGDfK peptide (CeNP+Dox+RGD) to target both gliomas and its tumor microenvironment (TME) via integrin receptors. Materials& methods: CeNP+Dox+RGD nanoparticles are synthesized by the sequential addition of cerium III chloride heptahydrate, beta-cyclodextrin, oleic acid, and F127 micelle (CeNP). Doxorubicin was then loaded into CeNPs and coated with oleyl amine-linked cyclic RGDfK peptide to form stable CeNP+Dox+RGD nanoparticles. Results: CeNP+Dox+RGD nanoparticles crossed blood-brain barrier (BBB) effectively and demonstrated threefold enhanced survivability in glioma-bearing mice. The IHC profiling of glial tumor cross-sections showed increased CD80 expression (M1 TAMs) and decreased arginase-1 expression (M2 TAMs). Conclusion: CeNP+Dox+RGD can be an immunotherapeutic treatment option to combat glioblastoma.

F127/chlorin e6-nanomicelles to enhance Ce6 solubility and PDT-efficacy mitigating lung metastasis in melanoma.

Photodynamic Therapy (PDT) is a promising paradigm for treating cancer, especially superficial cancers, including skin and oral cancers. However, the effectiveness of PDT is hindered by the hydrophobicity of photosensitizers. Here, chlorin e6 (Ce6), a hydrophobic photosensitizer, was loaded into pluronic F127 micelles to enhance solubility and improve tumor-specific targeting efficiency. The resulting Ce6@F127 Ms demonstrated a significant increase in solubility and singlet oxygen generation (SOG) efficiency in aqueous media compared to free Ce6. The confocal imaging and fluorescence-activated cell sorting (FACS) analysis confirmed the enhanced internalization rate of Ce6@F127 Ms in murine melanoma cell lines (B16F10) and human oral carcinoma cell lines (FaDu). Upon laser irradiation (666nm), the cellular phototoxicity of Ce6@F127 Ms against B16F10 and FaDu was approximately three times higher than the free Ce6 treatment. The in vivo therapeutic investigations conducted on a murine model of skin cancer demonstrated the ability of Ce6@F127 Ms, when combined with laser treatment, to penetrate solid tumors effectively, which resulted in a significant reduction in tumor volume compared to free Ce6. Further, the Ce6@F127 Ms demonstrated upregulation of TUNEL-positive cells, downregulation of proliferation markers in tumor tissues, and prevention of lung metastasis with insignificant levels of proliferating cells and collagenase, as validated through immunohistochemistry. Subsequent analysis of serum and blood components affirmed the safety and efficacy of Ce6@F127 Ms in mice. Consequently, the developed Ce6@F127 Ms exhibits significant potential for concurrently treating solid tumors and preventing metastasis. The photodynamic formulation holds great clinical translation potential for treating superficial tumors.

Nanostructured systems based on pluronics to carry gold nanoparticles and methylene blue aiming for multimodal therapy

The rise of multidrug-resistant microorganisms has become a cause of concern in the biomedical field. In this sense, this study focuses on the development of an effective treatment for infectious diseases mediated by Multimodal Therapy, combining Photodynamic Therapy (PDT), and Photothermal Therapy (PTT). The system involves the synthesis and stabilization of gold nanoparticles (AuNPs) in Pluronic® micelles of F-127 and P-84, combined with the Methylene Blue (MB) aiming effects against microorganisms. It is noteworthy that the AuNPs were synthesized in situ in the copolymer using the solid dispersion technique. These copolymers were strategically chosen for evaluation purposes with our study involving P-123 previously published in this journal. Thus, the effect of the length of the PEO and PPO blocks can be delineated concerning the synthesis of AuNPs. In this case, copolymer F127 has PPO blocks identical to P-123 while P-84 has PEO blocks compatible with P-123. Characterization of the formulations included electronic absorption spectroscopy, dynamic light scattering, and transmission electron microscopy. Fluorescence quenching studies by Stern Volmer plots indicated the location of the MB in the hydrophilic corona of the micelles. In general, was verified that reducing the PEO/PPO ratio favors the formation of AuNPs, possibly due to the greater number of reducing sites per unit mass of the polymer. The formulations remained stable for at least 15 days, and photothermal studies showed a temperature increase of at least 11 °C. The photothermal effect proved reversible after three heating–cooling cycles, revealing a synergy between MB and AuNPs in heat generation, hindered by increased irradiance and rapid photobleaching of MB. The in vitro susceptibility tests with Candida albicans and Staphylococcus aureus demonstrated effective inhibition of the microorganisms. The result shows that AuNPs for itself do not affect the fungal/bacteria lineage. However, the MB/AuNPs combination samples, showed excellent fungal and bacterial inhibition at low drug concentrations.

Enhancement of in-vivo cellular uptake of Coenzyme Q10 using saponin derivatives in rTALAP transgenic mice model

Pancreatic cancer remains a significant contributor to cancer-related mortality, with pancreatic ductal adenocarcinoma (PDAC) being particularly challenging to treat. Coenzyme Q10 (CoQ10), a hydrophobic antioxidant crucial for cellular energy production, holds promise in PDAC therapy. However, its limited solubility hinders efficient cellular uptake. To overcome this limitation, we developed micelle formulations incorporating CoQ10 and assessed their potential to enhance cellular delivery. In this particular study, we have utilized some of the most common saponins such as Quillaja saponin, Ginsenoside R0, and Ginsenoside Rb1 as a drug carrier in order to enhance the bioavailability and cellular uptake of CoQ10. Micelles' size and shape were characterized using DLS, TEM, and LC-MS/MS. These all saponin micelles showed better encapsulation, zeta potential, and smaller size compared to Pluronic F127 micelles. Moreover, these formulations induced a notable increase in reactive oxygen species (ROS) generation, indicative of potential apoptotic activity. Further investigations revealed that micelle treatments led to modulation of gene expression related to epithelial-mesenchymal transition (EMT) markers, with an increase in E-cadherin expression and a decrease in claudin, snail, slug, and vimentin. Additionally, in-vivo screening studies in transgenic mice demonstrated promising results as anticancer by reducing apoptosis. In conclusion, our findings suggest that CoQ10-loaded micelles, particularly those incorporating Quillaja saponin and ginsenoside derivatives, hold potential as a novel therapeutic approach for PDAC by enhancing cellular uptake, inducing ROS-mediated apoptosis, and modulating EMT markers. These findings contribute to advancing our understanding of CoQ10's role in pancreatic cancer therapy.

Amino-Functionalized Pluronic F127 micelles as a dual drug delivery nanostructure for controlled therapeutics release

Bacterial infection is one of the serious leading causes of hospitalization. The development of a novel dual drug delivery nanostructure based on polymeric micelles is presented here for the treatment of Staphylococcus aureus-associated infections. The nanostructure was composed of quercetin (QC)-encapsulated in the core of F127 micelles (FQ micelles) which was later shell cross-linked using 3-amisinopropyl triethoxysilane (APTES) molecules through condensation reaction. The functionalization of the head groups of FQ micelles with APTES (FQA NPs) facilitated the covalent linkage of vancomycin (Vanc) drug and consequent formation of FQA-Vanc NPs with the hydrodynamic size of 133 nm. FQA-Vanc NPs demonstrated prolong release of QC and Vanc over a period of 168 h. The core–shell structure offered sustainable release of Vanc and QC to the FQA-Vanc NPs during 96 h and 48 h, respectively. The co-administration of Vanc and QC not only enhanced the antibacterial performance of FQA-Vanc NPs, but also induced time and concentration-dependent antioxidant activities. Overall, the Vanc immobilized-FQA NPs together with antibacterial and antioxidant activities could potentially provide a new therapeutic platform for bacterial infection treatment.

Injectable and Conductive Nanomicelle Hydrogel with α-Tocopherol Encapsulation for Enhanced Myocardial Infarction Repair.

Substantial advancements have been achieved in the realm of cardiac tissue repair utilizing functional hydrogel materials. Additionally, drug-loaded hydrogels have emerged as a research hotspot for modulating adverse microenvironments and preventing left ventricular remodeling after myocardial infarction (MI), thereby fostering improved reparative outcomes. In this study, diacrylated Pluronic F127 micelles were used as macro-cross-linkers for the hydrogel, and the hydrophobic drug α-tocopherol (α-TOH) was loaded. Through the in situ synthesis of polydopamine (PDA) and the incorporation of conductive components, an injectable and highly compliant antioxidant/conductive composite FPDA hydrogel was constructed. The hydrogel exhibited exceptional stretchability, high toughness, good conductivity, cell affinity, and tissue adhesion. In a rabbit model, the material was surgically implanted onto the myocardial tissue, subsequent to the ligation of the left anterior descending coronary artery. Four weeks postimplantation, there was discernible functional recovery, manifesting as augmented fractional shortening and ejection fraction, alongside reduced infarcted areas. The findings of this investigation underscore the substantial utility of FPDA hydrogels given their proactive capacity to modulate the post-MI infarct microenvironment and thereby enhance the therapeutic outcomes of myocardial infarction.

Role of micelle dynamics in enhancing cyclosporine uptake in hyaluronic acid-contact lenses for improved critical lens properties in dry eye management

Loading hydrophobic drugs, such as cyclosporine, into contact lenses for dry eye treatment is challenging due to low drug uptake during soaking and alterations in critical lens properties, including wettability, water content, and optical transmission. This study aimed to investigate the role of micelle dynamics in enhancing cyclosporine loading into hyaluronic acid (HA)-contact lenses while improving their critical properties. The findings indicate that Pluronic® F127 (342 nm) and Tween® 80 (296 nm) micelles could encapsulate cyclosporine within the lens core, with Pluronic® F127 demonstrating superior surface tension on Langmuir-Blodgett trough compared to Tween® 80. The uptake of cyclosporine-loaded micelles (13.43–20.92 µg) was higher compared to cyclosporine without micelles (CY-CL = 8.80 µg). Moreover, the cyclosporine-loaded micelles improved the lens’s contact angle (wettability), equilibrium water content, and optical transmission compared to cyclosporine without micelles. The in vitro test showed sustained release of cyclosporine from contact lenses over 120 h or 96 h using Pluronic®-micelles or Tween® 80-micelles, respectively. In animal study, the 0.05% w/v Pluronic® F127-CL and 0.0015% w/v Tween 80-CL lenses showed an initial release of 2.54 µg/ml and 3.59 µg/ml, respectively, with the release profile extending over 48 h. Wear of the micelle-laden lenses resulted in lower levels of IL-6 compared to cyclosporine eye drops. In conclusion, Pluronic® F127 micelles demonstrated greater stability, sustained release, and improved outcomes compared to Tween® 80 micelles. These findings suggest the potential of micelles-laden contact lenses as a promising alternative to eye drops for improved dry eye management.

Design of Liquid Formulation Based on F127-Loaded Natural Dimeric Flavonoids as a New Perspective Treatment for Leishmaniasis.

Infectious and Parasitic Diseases (IPD) remain a challenge for medicine due to several interconnected reasons, such as antimicrobial resistance (AMR). American tegumentary leishmaniasis (ATL) is an overlooked IPD causing persistent skin ulcers that are challenging to heal, resulting in disfiguring scars. Moreover, it has the potential to extend from the skin to the mucous membranes of the nose, mouth, and throat in both humans and various animals. Given the limited effectiveness and AMR of current drugs, the exploration of new substances has emerged as a promising alternative for ATL treatment. Arrabidaea brachypoda (DC). Bureau is a native Brazilian plant rich in dimeric flavonoids, including Brachydin (BRA), which displays antimicrobial activity, but still little has been explored regarding the development of therapeutic formulations. In this work, we present the design of a low-cost liquid formulation based on the use of Pluronic F127 for encapsulation of high BRA concentration (LF-B500). The characterization techniques revealed that BRA-loaded F127 micelles are well-stabilized in an unusual worm-like form. The in vitro cytotoxicity assay demonstrated that LF-B500 was non-toxic to macrophages but efficient in the inactivation of forms of Leishmania amazonensis promastigotes with IC50 of 16.06 µg/mL. The results demonstrated that LF-B500 opened a new perspective on the use of liquid formulation-based natural products for ATL treatment.

Facile preparation of self-healing hydrogels based on chitosan and PVA with the incorporation of curcumin-loaded micelles for wound dressings

The increased demand for improved strategies for wound healing has, in recent years, motivated the development of multifunctional hydrogels with favorable bio-compatibility and antibacterial properties. To this regard, the current study presented the design of a novel self-healing composite hydrogel that could perform as wound dressing for the promotion of wound healing. The composite hydrogels were composed of polyvinyl alcohol (PVA), borax and chitosan functionalized with sialic acid (SA-CS) and curcumin loaded pluronic F127 micelles. The hydrogels were formed through the boronic ester bond formation between PVA, SA-CS and borax under physiological conditions and demonstrated adjustable mechanical properties, gelation kinetics and antibacterial properties. When incubating with NIH3T3 cells, the hydrogels also demonstrated good biocompatibility. These aspects offer a promising foundation for their prospective applications in developing clinical materials for wound healing.

Lysosome-targeted ruthenium(II) complex encapsulated with pluronic® F-127 induces oncosis in A549 cells.

Transition metal complexes with characteristics of unique packaging in nanoparticles and remarkable cancer cell cytotoxicity have emerged as potential alternatives to platinum-based antitumor drugs. Here we report the synthesis, characterization, and antitumor activities of three new Ruthenium complexes that introduce 5-fluorouracil-derived ligands. Notably, encapsulation of one such metal complex, Ru3, within pluronic® F-127 micelles (Ru3-M) significantly enhanced Ru3 cytotoxicity toward A549 cells by a factor of four. To determine the mechanisms underlying Ru3-M cytotoxicity, additional in vitro experiments were conducted that revealed A549 cell treatment with lysosome-targeting Ru3-M triggered oxidative stress, induced mitochondrial membrane potential depolarization, and drastically reduced intracellular ATP levels. Taken together, these results demonstrated that Ru3-M killed cells mainly via a non-apoptotic pathway known as oncosis, as evidenced by observed Ru3-M-induced cellular morphological changes including cytosolic flushing, cell swelling, and cytoplasmic vacuolation. In turn, these changes together caused cytoskeletal collapse and activation of porimin and calpain1 proteins with known oncotic functions that distinguished this oncotic process from other cell death processes. In summary, Ru3-M is a potential anticancer agent that kills A549 cells via a novel mechanism involving Ru(II) complex triggering of cell death via oncosis.

A 4D Printed Adhesive, Thermo-Contractile, and Degradable Hydrogel for Diabetic Wound Healing.

Chronic wound healing remains a substantial clinical challenge. Current treatments are often either prohibitively expensive or insufficient in meeting the various requirements needed for effective diabetic wound healing. A 4D printing multifunctional hydrogel dressing is reported here, which aligns perfectly with wounds owning various complex shapes and depths, promoting both wound closure and tissue regeneration. The hydrogel is prepared via digital light process (DLP) 3D printing of the mixture containing N-isopropylacrylamide (NIPAm), curcumin-loaded Pluronic F127 micelles (Cur-PF127), and poly(ethylene glycol) diacrylate-dopamine (PEGDA575-Do), a degradable crosslinker. The use of PEGDA575-Do ensures tissue adhesion and degradability, and cur-PF127 serves as an antibacterial agent. Moreover, the thermo-responsive mainchains (i.e., polymerized NIPAm) enables the activation of wound contraction by body temperature. The features of the prepared hydrogel, including robust tissue adhesion, temperature-responsive contraction, effective hemostasis, spectral antibacterial, biocompatibility, biodegradability, and inflammation regulation, contribute to accelerating diabetic wound healing in Methicillin-resistant Staphylococcus aureus (MRSA)-infected full-thickness skin defect diabetic rat models and liver injury mouse models, highlighting the potential of this customizable, mechanobiological, and inflammation-regulatory dressing to expedite wound healing in various clinical settings.

A novel bis(β-Br-BODIPY) photosensitizer and its nanoscale delivery systems based on polymer micelles and zeolite-like MOFs

The design of biocompatible photosensitizers with an optimal combination of intense fluorescence and generation of singlet oxygen is a complex and urgent task. The article presents the results of synthesizing, analyzing the structure, and examining the chromophoric, fluorescent, and generation characteristics of new dimeric bis(β-Br-BODIPY) (1), as well as the features of its encapsulation in ZIF-8 zeolite framework and solubilization by Pluronic® F127 micelles. The photophysical characteristics of brominated dimer 1 were analyzed in comparison with non-halogenated dimers bis(β-H-BODIPY) (2), bis(β-CH3-BODIPY) (3), as well as dibromo-substituted mononuclear analogue β,β-dibromo-BODIPY (4). Dye 1 exhibits efficient fluorescence (from 53 to 72%) and 1O2 generation (from 19 to 42%) in solutions of nonpolar and weakly polar solvents. Dimerization leads to a high sensitivity of the fluorescence and generation characteristics of the halogenated dimer 1 to the solvent. The advantage of dimer 1 is a significantly lower tendency to aggregate compared to monomer 4. The conditions for the encapsulation of dye 1 in ZIF-8 nanoparticles and Pluronic® F127 micelles were determined and their structural and spectral characteristics were analyzed.

An Ultra‐Small Osmium Clusters‐Loaded Organosilica‐Based Antibacterial Nanoagent for Efficient Infected‐Wound Healing

AbstractRecently, nanomaterials with natural enzymatic activity and photothermal effect offer an alternative pathway to combat bacterial infections and the abuse of antibiotics. Unfortunately, the development of these reported antibacterial nanoagents is always hampered by insufficient enzymatic activity and low photothermal conversion efficiency. To address these issues, herein, novel ultra‐small osmium clusters‐loaded F127‐organosilica micelles (Os@FOMs) are developed as antibacterial nanoagents for efficient infected‐wound healing. The preparation of nanoagents mainly involves the confined sol‐gel transition of thiol‐containing silane coupling agent in the hydrophobic region of F127 micelles and subsequent self‐reduction process of osmium salt in the thiols/disulfides‐doped organosilica framework. As a promising candidate for bacterial‐infected wound healing, Os@FOMs exhibit not only high photothermal conversion efficiency of 70% under 808 nm near infrared (NIR) irradiation, but also display peroxidase (POD)‐like activity in acidic conditions, which together contribute excellent antibacterial ability in acidic bacterial infectious microenvironment. On the other hand, Os@FOMs possess good catalase‐like effect in neutral or weak alkaline conditions, thus protecting normal tissues from the POD‐like protocol with exogenous H2O2 damage for efficient wound healing. It is highly expected that the new noble metal@organosilica‐based nanoagents present a promising paradigm to fight antibiotic‐resistant pathogens.

Subcutaneous Rapid Dissolution Microneedle Patch Integrated with CuO2 and Disulfiram for Augmented Antimelanoma Efficacy through Multimodal Synergy of Photothermal Therapy, Chemodynamic Therapy, and Chemotherapy.

Melanoma is a malignancy of the skin that is resistant to conventional treatment, necessitating the development of effective and safe new therapies. The percutaneous microneedle (MN) system has garnered increasing interest as a viable treatment option due to its high efficacy, minimal invasiveness, painlessness, and secure benefits. In this investigation, a sensitive MN system with multiple functions was created to combat melanoma effectively. This MN system utilized polyvinylpyrrolidone (PVP) as microneedle substrates and biocompatibility panax notoginseng polysaccharide (PNPS) as microneedle tips, which encapsulated PVP-stabilized CuO2 nanoparticles as a therapeutic agent and disulfiram-containing F127 micelles to enhance the tumor treatment effect. The MN system had sufficient mechanical properties to pierce the skin, and the excellent water solubility of PNPS brought high-speed dissolution properties under the bio conditions, allowing the MNs to effectively penetrate the skin and deliver the CuO2 nanoparticles as well as the drug-loaded micelles to the melanoma site. CuO2 nanoparticles released by the MN system generated Cu2+ and H2O2 in the tumor acidic environment to achieve self-supply of hydrogen peroxide to chemodynamic therapy (CDT). In addition, Cu2+ was chelated with disulfiram to produce CuET, which killed tumor cells. And the MN system had excellent near-infrared (NIR) photothermal properties due to the loading of CuO2 nanoparticles and induced localized thermotherapy in the melanoma region to further inhibit tumor growth. Thus, the designed MN system accomplished effective tumor suppression and minimal side effects in vivo via combined therapy, offering patients a safe and effective option for melanoma treatment.