Surface engineering of metal-organic framework nanoparticles-based miRNA carrier: Boosting RNA stability, intracellular delivery and synergistic therapy.

MicroRNAs (miRNAs) are small noncoding RNAs that are critical for the regulation of multiple physiological and pathological processes, thus holding great clinical potential. However, the therapeutic applications of miRNAs are severely limited by their biological instability and poor intracellular delivery. Herein, we describe a dual-layers surface engineering strategy to design an efficient miRNA delivery nanosystem based on metal-organic frameworks (MOFs) incorporating lipid coating. The resulting nanoparticle system was demonstrated to protect miRNA from ribonuclease degradation, enhance cellular uptake and facilitate lysosomal escape. These ensured effective miRNA mediated gene therapy, which synergized with MOF-specific photodynamic therapy and pre-encapsulated doxorubicin (Dox) chemotherapy to provide a multifunctional with therapeutic effectiveness against cencer cells The mechanisms of miRNA binding and Dox loading were revealed, demonstrating the potential of the present MOFs surface-engineered strategy to overcome their inherent pore-size restriction for macromolecular miRNA carrying, enableefficient co-delivery. In vitro studies revealed the potential of our multifunctional system for miRNA delivery and the demonstrated the therapeutic effectiveness against cancer cells, thereby providing a versatile all-in-one MOFs strategy for delivery of nucleic acids and diverse therapeutic molecules in synergistic therapy.

A computer-aided, heterodimer-based "triadic" carrier-free drug delivery platform to mitigate multidrug resistance in lung cancer and enhance efficiency.

Co-delivering multiple drugs or circumventing the drug efflux mechanism can significantly decrease multidrug resistance (MDR), a major cause of cancer treatment failure. In this study, we designed and fabricated a universal "three-in-one" self-delivery system for synergistic cancer therapy using a computer-aided strategy. First, we engineered two glutathione (GSH)-responsive heterodimers, ERL-SS-CPT (erlotinib [ERL] linked with camptothecin [CPT] via a disulfide bond [SS]) and CPT-SS-ERI (CPT conjugated with erianin [ERI]), which serve as both cargo and carrier material. Next, molecular dynamics simulations indicated that multiple noncovalent molecular forces, including π-π stacking, hydrogen bonds, hydrophobic interactions, and sulfur bonds, drive the self-assembly process of these heterodimers. We then explored the universality of the heterodimers and developed a "triadic" drug delivery platform comprising 40 variants. Subsequently, we conducted case studies on docetaxel (DTX)-loaded ERL-SS-CPT nanoparticles (denoted as DTX@ERL-SS-CPT NPs) and curcumin (CUR)-loaded ERL-SS-CPT NPs (identified as CUR@CPT-SS-ERI NPs) to comprehensively investigate their self-assembly mechanism, physicochemical properties, storage stability, GSH-responsive drug release, cellular uptake, apoptosis effects, biocompatibility, and cytotoxicity. Both NPs exhibited well-defined spherical structures, high drug loading rates, and excellent storage stability. DTX@ERL-SS-CPT NPs exhibited the strongest cytotoxicity in A549 cells, following the order of DTX@ERL-SS-CPT NPs > ERL-SS-CPT NPs > CPT > DTX > ERL. Conversely, DTX@ERL-SS-CPT NPs showed negligible cytotoxicity in normal human bronchial epithelium cell line (BEAS-2B), indicating good biocompatibility and safety. Similar observations were made for CUR@CPT-SS-ERI NPs regarding biocompatibility and cytotoxicity. Upon endocytosis and encountering intracellular overexpressed GSH, the disulfide-bond linker is cleaved, resulting in the release of the versatile NPs into three parts. The spherical NPs enhance water solubility, reduce the required dosage of free drugs, and increase cellular drug accumulation while suppressing P-glycoprotein (P-gp) expression, leading to apoptosis. This work provides a computer-aided universal strategy-a heterodimer-based "triadic" drug delivery platform-to enhance anticancer efficiency while reducing multidrug resistance.

Upconversion nanoparticles-CuMnO2 nanoassemblies for NIR-excited imaging of reactive oxygen species in vivo.

Here, we designed a ratiometric luminescent nanoprobe based on lanthanide-doped upconversion nanoparticles-CuMnO2 nanoassemblies for rapid and sensitive detection of reactive oxygen species (ROS) levels in living cells and mouse. CuMnO2 nanosheets exhibit a wide absorption range of 300-700 nm, overlapping with the visible-light emission of upconversion nanoparticles (UCNPs), resulting in a significant upconversion luminescence quenching. In an acidic environment, H2O2 can promote the redox reaction of CuMnO2, leading to its dissociation from the surface of UCNPs and the restoration of upconversion luminescence. The variation in luminescence intensity ratio (UCL475/UCL450) were monitored to detect ROS levels. The H2O2 nanoprobe exhibited a linear response in the range of 0.314-10 µM with a detection limit of 11.3 nM. The biological tests proved the excellent biocompatibility and low toxicity of obtained UCNPs-CuMnO2 nanoassemblies. This ratiometric luminescent nanoprobe was successfully applied for the detection of exogenous and endogenous ROS in live cells as well as in vivo ROS quantitation. The dual transition metal ions endow this probe efficient catalytic decomposition capabilities, and this sensing strategy broadens the application of UCNPs-based nanomaterials in the field of biological analysis and diagnosis.

Cubosomes and hexosomes stabilized by sorbitan monooleate as biocompatible nanoplatforms against skin metastatic human melanoma.

Nanoparticles have become versatile assets in the medical field, providing notable benefits across diverse medical arenas including controlled drug delivery, imaging, and immunological assays. Among these, non-lamellar lipid nanoparticles, notably cubosomes and hexosomes, showcase remarkable biocompatibility and stability, rendering them as optimal choices for theranostic applications. Particularly, incorporating edge activators like sodium taurocholate enhances the potential of these nanoparticles for dermal and transdermal drug delivery, overcoming the stratum corneum, a first line of defense in our skin. This study reports on the formulation of monoolein-based cubosomes and hexosomes incorporating taurocholate and stabilized by Span 80 and co-encapsulating Chlorin e6 and coenzyme QH for photodynamic therapy in skin metastatic melanoma. The formulations were optimized using small-angle X-ray scattering, and cryo-transmission electron microscopy confirmed the presence of cubosomes or hexosomes, depending on the ratio between taurocholate and Span 80. Furthermore, the co-loaded nanoparticles exhibited high encapsulation efficiencies for both Ce6 and the coenzyme QH. In vitro studies on human melanoma cells (Me45) demonstrated the biocompatibility and photodynamic activity of the loaded formulations. These findings show the possibility of formulating more biocompatible cubosomes and hexosomes for photodynamic therapy in skin cancer treatment.

Revealing the impact of modified modules flexibility on gemcitabine prodrug nanoassemblies for effective cancer therapy.

Prodrug nanoassemblies combine the advantages of prodrug strategies and nanotechnology have been widely utilized for delivering antitumor drugs. These prodrugs typically comprise active drug modules, response modules, and modification modules. Among them, the modification modules play a critical factor in improving the self-assembly ability of the parent drug. However, the impact of the specific structure of the modification modules on prodrug self-assembly remains elusive. In this study, two gemcitabine (GEM) prodrugs are developed using 2-octyl-1-dodecanol (OD) as flexible modification modules and cholesterol (CLS) as rigid modification modules. Interestingly, the differences in the chemical structure of modification modules significantly affect the assembly performance, drug release, cytotoxicity, tumor accumulation, and antitumor efficacy of prodrug nanoassemblies. It is noteworthy that the prodrug nanoassemblies constructed with flexible modifying chains (OD) exhibit improved stability, faster drug release, and enhanced antitumor effects. Our findings elucidate the significant impact of modification modules on the construction of prodrug nanoassemblies.

Cubosome lipid nanocarriers for delivery of ultra-short antimicrobial peptides.

HYPOTHESIS: Although antimicrobial peptides (AMPs) are a promising class of new antibiotics, their inherent susceptibility to degradation requires nanocarrier-mediated delivery. While cubosome nanocarriers have been extensively studied for delivery of AMPs, we do not currently understand why cubosome encapsulation improves antimicrobial efficacy for some compounds but not others. This study therefore aims to investigate the link between the mechanism of action and permeation efficiency of the peptides, their encapsulation efficacy, and the antimicrobial activity of these systems. EXPERIMENTS: Encapsulation and delivery of Indolicidin, and its ultra-short derivative, Priscilicidin, were investigated using SAXS, cryo-TEM and circular dichroism. Molecular dynamics simulations were used to understand the loading of these peptides within cubosomes. The antimicrobial efficacy was assessed against gram-negative (E. coli) and gram-positive (MRSA) bacteria. FINDINGS: A high ionic strength solution was required to facilitate high loading of the cationic AMPs, with bilayer encapsulation driven by tryptophan and Fmoc moieties. Cubosome encapsulation did not improve the antimicrobial efficacy of the AMPs consistent with their high permeation, as explained by a recent 'diffusion to capture model'. This suggests that cubosome encapsulation may not be an effective strategy for all antimicrobial compounds, paving the way for improved selection of nanocarriers for AMPs, and other antimicrobial compounds.

Specific buffer effects on the formation of BSA protein corona around amino-functionalized mesoporous silica nanoparticles.

The effect of buffer species on biomolecules and biomolecule-nanoparticle interactions is a phenomenon that has been either neglected, or not understood. Here, we study the formation of a BSA protein corona (PC) around amino-functionalized mesoporous silica nanoparticles (MSN-NH2) in the presence of different buffers (Tris, BES, cacodylate, phosphate, and citrate) at the same pH (7.15) and different concentrations (10, 50, and 100 mM). We find that BSA adsorption is buffer specific, with the adsorbed amount of BSA being 4.4 times higher in the presence of 100 mM Tris (184 ± 3 mg/g) than for 100 mM citrate (42 ± 2 mg/g). That is a considerable difference that cannot be explained by conventional theories. The results become clearer if the interaction energies between BSA and MSN-NH2, considering the electric double layer (EEDL) and the van der Waals (EvdW) terms, are evaluated. The buffer specific PC derives from buffer specific zeta potentials that, for MSN-NH2, are positive with Tris and negative with citrate buffers. A reversed sign of zeta potentials can be obtained by considering polarizability-dependent dispersion forces acting together with electrostatics to give the buffer specific outcome. These results are relevant not only to our understanding of the formation of the PC but may also apply to other bio- and nanosystems in biological media.

The immunological and pharmacokinetic evaluation of Lipid-PLGA hybrid nanoparticle-based oxycodone vaccines.

The current opioid epidemic is one of the most profound public health crises facing the United States. Despite that it has been under the spotlight for years, available treatments for opioid use disorder (OUD) and overdose are limited to opioid receptor ligands such as the agonist methadone and the overdose reversing drugs such as naloxone. Vaccines are emerging as an alternative strategy to combat OUD and prevent relapse and overdose. Most vaccine candidates consist of a conjugate structure containing the target opioid attached to an immunogenic carrier protein. However, conjugate vaccines have demonstrated some intrinsic shortfalls, such as fast degradation and poor recognition by immune cells. To overcome these challenges, we proposed a lipid-PLGA hybrid nanoparticle (hNP)-based vaccine against oxycodone (OXY), which is one of the most frequently misused opioid analgesics. The hNP-based OXY vaccine exhibited superior immunogenicity and pharmacokinetic efficacy in comparison to its conjugate vaccine counterpart. Specifically, the hNP-based OXY vaccine formulated with subunit keyhole limpet hemocyanin (sKLH) as the carrier protein and aluminum hydroxide (Alum) as the adjuvant (OXY-sKLH-hNP(Alum)) elicited the most potent OXY-specific antibody response in mice. The induced antibodies efficiently bound with OXY molecules in blood and suppressed their entry into the brain. In a following dose-response study, OXY-sKLH-hNP(Alum) equivalent to 60 µg of sKLH was determined to be the most promising OXY vaccine candidate moving forward. This study provides evidence that hybrid nanoparticle-based vaccines may be superior vaccine candidates than conjugate vaccines and will be beneficial in treating those suffering from OUD.

Current Review on Nanophytomedicines in the Treatment of Oral Cancer: Recent Trends and Treatment Prospects.

Cancer is one of the major life-threatening diseases in the world and oral cancer is the 8th most common type of deadly cancers in Asian countries. Despite many causes, tobacco is the main causative agent as 90% of oral cancer cases were due to daily consumption of tobacco and its products. The major drawback of the conventional therapies for oral cancer including chemotherapy, surgery and radiotherapy or combination of these is the dose limiting toxicity. Developments in technology and research led to new innovative discoveries in cancer treatments. In the past few decades, increased attention has been given to researches in alternative cancer treatment strategies using plants and plant products. Recently many anticancer drugs from natural products or phytochemicals were approved internationally. Due to the low bioavailability and poor solubility of phytochemicals, various research works on nano-carrier based drug delivery systems were exploited in the recent past to make them as promising anticancer agents. In the current review, an overview of oral cancer and its treatment, risk factors, missing links of conventional therapies, contribution of nanotechnology in cancer treatment and research on phytochemical based drug treatment and different polymeric nanoparticles were discussed briefly. The future prospects for the use of various types of polymeric nanoparticles applied in the diagnosis and treatment of oral cancer were also mentioned. The major concern of this review is to give the reader a better understanding on various types of treatment for oral cancer.

Nanobiocatalysis: Approach and Applications in Drug Development and Sensing.

Enzymes play a pivotal role in the human body, but their potential is not limited to just that. Scientists have successfully modified these enzymes as nanobiocatalysts or nanozymes for industrial or commercial use, either in the food, medicine, biotech or even textile industries. These nanobiocatalysts and nanozymes offer several advantages over enzymes, like better stability, improved shelf-life, increased percentage yield, and reuse potential, which is very difficult with normal enzymes. The various techniques of NBC synthesis using immobilization techniques like adsorption, covalent binding, affinity immobilization, and entrapment methods are briefly discussed. The enzymes are either entrapped or adsorbed on the nanocarrier matrices, which can be nanofibers, nanoporous carriers, or nanocontainers as nanobiocatalysts. We also highlight the challenges the nanobiocatalyst overcomes in the industrial production of some drugs like sitagliptin, montelukast, pregabalin, and atorvastatin. Also, the inactivation of an organophosphate or opioid poisoning treating agent, SSOPOX nanohybrid, is discussed in this paper. Nanozymes are intrinsic enzyme-like compounds, and they also show wide application in themselves. Their GQD/AGNP nanohybrid shows antibacterial potential; they can also be utilized in optical sensing to detect small molecules, ions, nucleic acids, proteins, and cancer cells. In this paper, various applications of these NBCs have been discussed, and their potential applications with examples are also mentioned. Nanoenzymes can address targeted drug delivery via the controlled release of drugs to increase the efficacy of anticancer drugs that minimize damage to healthy tissue or cells.

A carrier-free nanovaccine combined with cancer immunotherapy overcomes gemcitabine resistance.

Drug resistance is a significant challenge in cancer chemotherapy and is a primary factor contributing to poor recovery for cancer patients. Although drug-loaded nanoparticles have shown promise in overcoming chemotherapy resistance, they often carry a combination of drugs and require advanced design and manufacturing processes. Furthermore, they seldom approach chemotherapy-resistant tumors from an immunotherapy perspective. In this study, we developed a therapeutic nanovaccine composed solely of chemotherapy-induced resistant tumor antigens (CIRTAs) and the immune adjuvant Toll-like receptor (TLR) 7/8 agonist R848 (CIRTAs@R848). This nanovaccine does not require additional carriers and has a simple production process. It efficiently delivers antigens and immune stimulants to dendritic cells (DCs) simultaneously, promoting DCs maturation. CIRTAs@R848 demonstrated significant tumor suppression, particularly when used in combination with the immune checkpoint blockade (ICB) anti-PD-1 (αPD-1). The combined therapy increased the infiltration of T cells into the tumor while decreasing the proportion of regulatory T cells (Tregs) and modulating the tumor microenvironment, resulting in long-term immune memory. Overall, this study introduces an innovative strategy for treating chemotherapy-resistant tumors from a novel perspective, with potential applications in personalized immunotherapy and precision medicine.

MSCs biomimetic ultrasonic phase change nanoparticles promotes cardiac functional recovery after acute myocardial infarction.

Acute Myocardial Infarction (AMI) has seen rising cases, particularly in younger people, leading to public health concerns. Standard treatments, like coronary artery recanalization, often don't fully repair the heart's microvasculature, risking heart failure. Advances show that Mesenchymal Stromal Cells (MSCs) transplantation improves cardiac function after AMI, but the harsh microenvironment post-AMI impacts cell survival and therapeutic results. MSCs aid heart repair via their membrane proteins and paracrine extracellular vesicles that carry microRNA-125b, which regulates multiple targets, preventing cardiomyocyte death, limiting fibroblast growth, and combating myocardial remodeling after AMI. This study introduces ultrasound-responsive phase-change bionic nanoparticles, leveraging MSCs' natural properties. These particles contain MSC membrane and microRNA-125b, with added macrophage membrane for stability. Using Ultrasound Targeted Microbubble Destruction (UTMD), this method targets the delivery of MSC membrane proteins and microRNA-125b to AMI's inflamed areas. This aims to enhance cardiac function recovery and provide precise, targeted AMI therapy.

"All in one" lipid-polymer nanodelivery system for gene therapy of ischemic diseases.

Gene therapy offers a promising avenue for treating ischemic diseases, yet its clinical efficacy is hindered by the limitations of single gene therapy and the high oxidative stress microenvironment characteristic of such conditions. Lipid-polymer hybrid vectors represent a novel approach to enhance the effectiveness of gene therapy by harnessing the combined advantages of lipids and polymers. In this study, we engineered lipid-polymer hybrid nanocarriers with tailored structural modifications to create a versatile membrane fusion lipid-nuclear targeted polymer nanodelivery system (FLNPs) optimized for gene delivery. Our results demonstrate that FLNPs facilitate efficient cellular uptake and gene transfection via membrane fusion, lysosome avoidance, and nuclear targeting mechanisms. Upon encapsulating Hepatocyte Growth Factor plasmid (pHGF) and Catalase plasmid (pCAT), HGF/CAT-FLNPs were prepared, which significantly enhanced the resistance of C2C12 cells to H2O2-induced injury in vitro. In vivo studies further revealed that HGF/CAT-FLNPs effectively alleviated hindlimb ischemia-induced gangrene, restored motor function, and promoted blood perfusion recovery in mice. Metabolomics analysis indicated that FLNPs didn't induce metabolic disturbances during gene transfection. In conclusion, FLNPs represent a versatile platform for multi-dimensional assisted gene delivery, significantly improving the efficiency of gene delivery and holding promise for effective synergistic treatment of lower limb ischemia using pHGF and pCAT.

Trojan-horse inspired nanoblaster: X-ray triggered spot attack on radio-resistant cancer through radiodynamic therapy.

Radiotherapy as a mainstay of in-depth cervical cancer (CC) treatment suffers from its radioresistance. Radiodynamic therapy (RDT) effectively reverses radio-resistance by generating reactive oxygen species (ROS) with deep tissue penetration. However, the photosensitizers stimulated by X-ray have high toxicity and energy attenuation. Therefore, X-ray responsive diselenide-bridged mesoporous silica nanoparticles (DMSNs) are designed, loading X-ray-activated photosensitizer acridine orange (AO) for spot blasting RDT like Trojan-horse against radio-resistance cervical cancer (R-CC). DMSNs can encapsulate a large amount of AO, in the tumor microenvironment (TME), which has a high concentration of hydrogen peroxide, X-ray radiation triggers the cleavage of diselenide bonds, leading to the degradation of DMSNs and the consequent release of AO directly at the tumor site. On the one hand, it solves the problems of rapid drug clearance, adverse distribution, and side effects caused by simple AO treatment. On the other hand, it fully utilizes the advantages of highly penetrating X-ray responsive RDT to enhance radiotherapy sensitivity. This approach results in ROS-induced mitochondria damage, inhibition of DNA damage repair, cell cycle arrest and promotion of cancer cell apoptosis in R-CC. The X-ray responsive DMSNs@AO hold considerable potential in overcoming obstacles for advanced RDT in the treatment of R-CC.

Tumor microenvironment immunomodulation by nanoformulated TLR 7/8 agonist and PI3k delta inhibitor enhances therapeutic benefits of radiotherapy.

Infiltration of immunosuppressive cells into the breast tumor microenvironment (TME) is associated with suppressed effector T cell (Teff) responses, accelerated tumor growth, and poor clinical outcomes. Previous studies from our group and others identified infiltration of immunosuppressive myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) as critical contributors to immune dysfunction in the orthotopic claudin-low tumor model, limiting the efficacy of adoptive cellular therapy. However, approaches to target these cells in the TME are currently lacking. To overcome this barrier, polymeric micellular nanoparticles (PMNPs) were used for the co-delivery of small molecule drugs activating Toll-like receptors 7 and 8 (TLR7/8) and inhibiting PI3K delta (PI3Kδ). The immunomodulation of the TME by TLR7/8 agonist and PI3K inhibitor led to type 1 macrophage polarization, decreased MDSC accumulation and selectively decreased tissue-resident Tregs in the TME, while enhancing the T and B cell adaptive immune responses. PMNPs significantly enhanced the anti-tumor activity of local radiation therapy (RT) in mice bearing orthotopic claudin-low tumors compared to RT alone. Taken together, these data demonstrate that RT combined with a nanoformulated immunostimulant diminished the immunosuppressive TME resulting in tumor regression. These findings set the stage for clinical studies of this approach.

A cuproptosis-based nanomedicine suppresses triple negative breast cancers by regulating tumor microenvironment and eliminating cancer stem cells.

Cuproptosis is a new kind of cell death that depends on delivering copper ions into mitochondria to trigger the aggradation of tricarboxylic acid (TCA) cycle proteins and has been observed in various cancer cells. However, whether cuproptosis occurs in cancer stem cells (CSCs) is unexplored thus far, and CSCs often reside in a hypoxic tumor microenvironment (TME) of triple negative breast cancers (TNBC), which suppresses the expression of the cuproptosis protein FDX1, thereby diminishing anticancer efficacy of cuproptosis. Herein, a ROS-responsive active targeting cuproptosis-based nanomedicine CuET@PHF is developed by stabilizing copper ionophores CuET nanocrystals with polydopamine and hydroxyethyl starch to eradicate CSCs. By taking advantage of the photothermal effects of CuET@PHF, tumor hypoxia is overcome via tumor mechanics normalization, thereby leading to enhanced cuproptosis and immunogenic cell death in 4T1 CSCs. As a result, the integration of CuET@PHF and mild photothermal therapy not only significantly suppresses tumor growth but also effectively inhibits tumor recurrence and distant metastasis by eliminating CSCs and augmenting antitumor immune responses. This study presents the first evidence of cuproptosis in CSCs, reveals that disrupting hypoxia augments cuproptosis cancer therapy, and establishes a paradigm for potent cancer therapy by simultaneously eliminating CSCs and boosting antitumor immunity.

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.

A versatile nanoplatform carrying cascade Pt nanozymes remodeling tumor microenvironment for amplified sonodynamic/chemo therapy of thyroid cancer.

Thyroid cancer is increasing globally, with anaplastic thyroid carcinoma (ATC) being the most aggressive type and having a poor prognosis. Current clinical treatments for thyroid cancer present numerous challenges, including invasiveness and the necessity of lifelong medication. Furthermore, a significant portion of patients with ATC experience cancer recurrence and metastasis. To overcome this dilemma, we developed a pH-responsive biomimetic nanocarrier (CLP@HP-A) through the incorporation of Chlorin e6 (Ce6) and Lenvatinib (Len) within hollow polydopamine nanoparticles (HP) that were further modified with platinum nanoparticles (Pt), enabling synergistic chemotherapy and sonodynamic therapy. The CLP@HP-A nanocarriers exhibited specific binding with galectin-3 receptors, facilitating their internalization through receptor-mediated endocytosis for targeted drug delivery. Upon exposure to ultrasound (US) irradiation, Ce6 rapidly generated reactive oxygen species (ROS) to induce significant oxidative stress and trigger apoptosis in tumor cells. Additionally, Pt not only alleviated tumor hypoxia by catalyzing the conversion of H2O2 to oxygen (O2) but also augmented intracellular ROS levels through the production of hydroxyl radicals (•OH), thereby enhancing the efficacy of sonodynamic therapy. Moreover, Len demonstrated a potent cytotoxic effect on thyroid cancer cells through the induction of apoptosis. Transcriptomics analysis findings additionally corroborated that CLP@HP-A effectively triggered cancer cell apoptosis, thereby serving as a crucial mechanism for its cytotoxic effects. In conclusion, the integration of sonodynamic/chemo combination therapy with targeted drug delivery systems offers a novel approach to the management of malignant tumors.

Application of new tetra-cationic imidazolium ionic liquids for capture and conversion of CO2 to amphiphilic calcium carbonate nanoparticles as a green additive in water based drilling fluids.

Conversion and capture of carbon pollutants based on carbon dioxide to valuable green oil-field chemicals are target all over the world for controlling the global warming. The present article used new room temperature amphiphilic imidazolium ionic liquids with superior surface activity in the aqueous solutions to convert carbon dioxide gas to superior amphiphilic calcium carbonate nanoparticles. In this respect, tetra-cationic ionic liquids 2-(4-dodecyldimethylamino) phenyl)-1,3-bis (3-dodecyldimethylammnonio) propyl) bromide-1-H-imidazol-3-ium acetate and 2-(4-hexyldimethylamino) phenyl)-1,3-bis(3-hexcyldimethylammnonio) propyl) bromide-1 H-imidazol-3-ium acetate were prepared. Their chemical structures, thermal as well as their carbon dioxide absorption/ desorption characteristics were evaluated. They were used as solvent and capping agent to synthesize calcium carbonate nanoparticles with controlled crystalline lattice, sizes, thermal properties and spherical surface morphologies. The prepared calcium carbonate nanoparticles were used as additives for the commercial water based drilling mud to improve their filter lose and rheology. The data confirm that the lower concentrations of 2-(4-dodecyldimethylamino) phenyl)-1,3-bis (3-dodecyldimethylammnonio) propyl) bromide-1-H-imidazol-3-ium acetate achieved lower seawater filter lose and improved viscosities.

Engineering mesoporous polydopamine-based potentiate STING pathway activation for advanced anti-biofilm therapy.

The biofilm-induced "relatively immune-compromised zone" creates an immunosuppressive microenvironment that is a significant contributor to refractory infections in orthopedic endophytes. Consequently, the manipulation of immune cells to co-inhibit or co-activate signaling represents a crucial strategy for the management of biofilm. This study reports the incorporation of Mn2+ into mesoporous dopamine nanoparticles (Mnp) containing the stimulator of interferon genes (STING) pathway activator cGAMP (Mncp), and outer wrapping by M1-like macrophage cell membrane (m-Mncp). The cell membrane enhances the material's targeting ability for biofilm, allowing it to accumulate locally at the infectious focus. Furthermore, m-Mncp mechanically disrupts the biofilm through photothermal therapy and induces antigen exposure through photodynamic therapy-generated reactive oxygen species (ROS). Importantly, the modulation of immunosuppression and immune activation results in the augmentation of antigen-presenting cells (APCs) and the commencement of antigen presentation, thereby inducing biofilm-specific humoral immunity and memory responses. Additionally, this approach effectively suppresses the activation of myeloid-derived suppressor cells (MDSCs) while simultaneously boosting the activity of T cells. Our study showcases the efficacy of utilizing m-Mncp immunotherapy in conjunction with photothermal and photodynamic therapy to effectively mitigate residual and recurrent infections following the extraction of infected implants. As such, this research presents a viable alternative to traditional antibiotic treatments for biofilm that are challenging to manage.