Biomimetic Magnetic Nanoparticles Research Articles

The importance of cell uptake in photothermal treatments mediated by biomimetic magnetic nanoparticles

Biomimetic magnetic nanoparticles (BMNPs) mediated by MamC have proven to be photothermal agents able to allow an optimized cytotoxicity against tumoral cells when used simultaneously as drug nanotransporters and as hyperthermia agents. However, it remains unclear whether BMNPs need to be internalized by the cells and/or if there is a threshold for internal Fe concentration for the photothermal therapy to be effective. In this study, three different situations for photothermal treatments have been simulated to disentangle the effect of BMNPs cell uptake on cell viability after photothermal treatments. Human hepatoblastoma (HepG2) cell line was treated with suspensions of BMNPs, and protocols were developed to have only intracellular BMNPs, only extracellular BMNPs or both, followed by photothermal exposure of the treated cell cultures. Our data demonstrate that: (1) Although the heating efficiency of the photothermal agent is not altered by its location (intra/extracellular), the intracellular location of BMNPs is crucial to ensure the cytotoxic effect of photothermal treatments, especially at low Fe concentration. In fact, the concentration of BMNPs needed to reach the same cytotoxic effect following upon laser irradiation of 0.2 W/cm2 is three times larger if BMNPs are located extracellularly compared to that needed if BMNPs are located intracellularly; (2) For a given location of the BMNPs, cell death increases with BMNPs (or Fe) concentration. When BMNPs are located intracellularly, there is a threshold for Fe concentration (∼ 0.5 mM at laser power intensities of 0.1 W/cm2) needed to affect cell viability following upon cell exposure to photothermia. (3) Bulk temperature rise is not the only factor accounting for cell death. Actually, temperature increases inside the cells cause more damage to cell structures and trigger cell death more efficiently than an increase in the temperature outside the cell.

MAb-Functionalized Biomimetic MamC-Mediated-Magnetoliposomes as Drug Delivery Systems for Cancer Therapy.

In cancer therapy, new therapeutic nanoformulations able to mediate targeted chemotherapy are required. Recently, biomimetic magnetic nanoparticles (BMNPs) mediated by MamC, a magnetosome protein from Magnetococcus marinus MC-1, have proven, in vitro and in vivo, to be effective drug nanocarriers (following the application of an external gradient magnetic field) and to allow combination with hyperthermia. However, these nanoassemblies require further optimization to improve cytocompatibility, stability and active targeting ability. Herein, we describe the production of the magnetoliposomes (LP) embedding BMNPs functionalized (or not) with doxorubicin (DOXO), [LP(+/-DOXO-BMNPs)], and their surface modification with the DO-24 mAb, which targets the human Met/HGF receptor's ectodomain (overexpressed in many cancers). Nanoformulations were extensively characterized using TEM, DLS, FTIR and when tested in vitro, the lipid coating increased the colloidal stability and their biocompatibility, favoring the cellular uptake in cells overexpressing the cognate receptor. Indeed, the magnetoliposomes mAb-LP(+/-DOXO-BMNPs) exerted a specific active targeting ability by the presence of the mAb that preserved its immunocompetence. Both LP(BMNPs) and mAb-LP(BMNPs) were not toxic to cells, while +/-mAb-LP(DOXO-BMNPs) nanoformulations were indeed cytotoxic. Therefore, this study represents a proof of concept for the development of promising drug carriers for cancer therapy based on local chemotherapy directed by mAbs.

Nanoassemblies of acetylcholinesterase and β-lactamase immobilized on magnetic nanoparticles as biosensors to detect pollutants in water.

The use of enzymes immobilized on magnetic nanoparticles to detect contaminants in aqueous samples has gained interest, since it allows the magnetic control, concentration and reuse of the enzymes. In this work, the detection of trace amounts of organophosphate pesticides (chlorpyrifos) and antibiotics (penicillin G) in water was attained by developing a nanoassembly formed by either inorganic or biomimetic magnetic nanoparticles used as substrates to immobilize acetylcholinesterase (AChE) and β-lactamase (BL). Other than the substrate, the optimization of the nanoassembly was done by testing enzyme immobilization both through electrostatic interaction (also reinforced with glutaraldehyde) and covalent bonds (by carbodiimide chemistry). Temperature (25°C), ionic strength (150mM NaCl) and pH (7) were set to ensure enzymatic stability and to allow both the nanoparticles and the enzymes to present ionic charges that would allow electrostatic interaction. Under these conditions, the enzyme load on the nanoparticles was ⁓0.1mg enzyme per mg nanoparticles, and the preserved activity after immobilization was 50-60% of the specific activity of the free enzyme, being covalent bonding the one which yielded better results. Covalent nanoassemblies could detect trace concentrations of pollutants down to 1.43nM chlorpyrifos and 0.28nM penicillin G. They even permitted the quantification of 14.3μM chlorpyrifos and 2.8μM penicillin G. Also, immobilization conferred higher stability to AChE (⁓94% activity after 20 days storage at 4°C) and allowed to reuse the BL up to 12 cycles.

Biomimetic magnetic nanoparticles for bacterial magnetic concentration in liquids and qPCR-detection

Biomimetic magnetic nanoparticles for bacterial magnetic concentration in liquids and qPCR-detection

The Future of Interventions for Stage IV Colorectal Cancers

AbstractFuture options for the management of stage IV colorectal cancer are primarily focused on personalized and directed therapies. Interventions include precision cancer medicine, utilizing nanocarrier platforms for directed chemotherapy, palliative pressurized intraperitoneal aerosol chemotherapy (PIPAC), adjunctive oncolytic virotherapy, and radioembolization techniques. Comprehensive genetic profiling provides specific tumor-directed therapy based on individual genetics. Biomimetic magnetic nanoparticles as chemotherapy delivery systems may reduce systemic side effects of traditional chemotherapy by targeting tumor cells and sparing healthy cells. PIPAC is a newly emerging option for patients with peritoneal metastasis from colorectal cancer and is now being used internationally, showing promising results as a palliative therapy for colorectal cancer. Oncolytic virotherapy is another emerging potential treatment option, especially when combined with standard chemotherapy and/or radiation, as well as immunotherapy. And finally, radioembolization with yttrium-90 (90Y) microspheres has shown some success in treating patients with unresectable liver metastasis from colorectal cancer via selective arterial injection.

Effects of Magnetic Nanoparticles on the Functional Activity of Human Monocytes and Dendritic Cells.

The use of nanoparticles in medicine is sometimes hampered by their potential to activate immune cells, eliciting inflammation or allergy. We investigated whether magnetic nanoparticles (MNPs) or biomimetic magnetic nanoparticles (BMNPs) affect relevant activities of human monocytes. We found that the nanoparticles neither elicited the production of pro-inflammatory mediators IL-6 and TNFα by resting monocytes (when BMNP dose < 300 μg/mL) nor enhanced their secretion induced by R848, a molecule engaging virus-recognizing receptors, or bacterial lipopolysaccharide (LPS). MNPs and BMNPs neither induced the generation of reactive oxygen species (ROS), nor affected the ROS production elicited by the NADPH oxidase activator phorbol myristate acetate (PMA) or the fungal derivative β-glucan. BMNPs, but not MNPs, caused an up-regulation of the maturation markers CD80, CD83, and CD86 in immature monocyte-derived dendritic cells (DCs), whereas both nanoparticles did not affect the LPS-induced expression of these markers. Moreover, the nanoparticles were greedily ingested by monocytes and DCs without altering their viability. Therefore, these nanoparticles are candidates for medical applications because they do not activate pro-inflammatory activities of monocytes. Furthermore, their ability to stimulate DC maturation could be used for the design of vaccines. Moreover, harmlessly engulfed nanoparticles could be vehicles to carry molecules inside the immune cells to regulate the immune response.

Inside-out extracellular vesicles-like biomimetic magnetic nanoparticles for efficient screening P-Glycoprotein inhibitors to overcome cancer multidrug resistance

The discovery of P-Glycoprotein (P-gp) inhibitors to block chemotherapy drugs efflux is considered an attractive treatment strategy for overcoming cancer multidrug resistance (MDR). Cell membrane biomimetic platform has emerged as a promising candidate method for screening small molecule P-gp inhibitors from natural products. However, randomly oriented cell membrane coating does not guarantee the inward-opening conformation of P-gp, limiting the precise screening of P-gp inhibitors. Herein, inside-out orientation extracellular vesicles camouflaged magnetic nanoparticles (IOVMNPs) were prepared to discover P-gp inhibitors with low toxicity and high efficiency from natural products. The orientation of extracellular vesicles on the surface of IOVMNPs was rigorously confirmed by immunogold electron microscopy and sialic acid quantification assay. Finally, two potential P-gp inhibitors, honokiol and magnolol, were captured by obtained IOVMNPs. The effect of MDR reversal in combination with chemotherapy drugs was further verified by pharmacological activity experiments. The inside-out orientation extracellular vesicles encapsulation strategy provides an effective tool for the discovery of novel P-gp inhibitors from nature products, thus further extending the application field of orientation assembly cell membrane biomimetic magnetic nanoparticles. This inside-out extracellular vesicles coating also proposes a new concept for the assembly of cell membrane biomimetic platform.

Embedding Biomimetic Magnetic Nanoparticles Coupled with Peptide AS-48 into PLGA to Treat Intracellular Pathogens.

Among the strategies employed to overcome the development of multidrug-resistant bacteria, directed chemotherapy combined with local therapies (e.g., magnetic hyperthermia) has gained great interest. A nano-assembly coupling the antimicrobial peptide AS-48 to biomimetic magnetic nanoparticles (AS-48-BMNPs) was demonstrated to have potent bactericidal effects on both Gram-positive and Gram-negative bacteria when the antimicrobial activity of the peptide was combined with magnetic hyperthermia. Nevertheless, intracellular pathogens remain challenging due to the difficulty of the drug reaching the bacterium. Thus, improving the cellular uptake of the nanocarrier is crucial for the success of the treatment. In the present study, we demonstrate the embedding cellular uptake of the original nano-assembly into THP-1, reducing the toxicity of AS-48 toward healthy THP-1 cells. We optimized the design of PLGA[AS-48-BMNPs] in terms of size, colloidal stability, and hyperthermia activity (either magnetic or photothermal). The stability of the nano-formulation at physiological pH values was evaluated by studying the AS-48 release at this pH value. The influence of pH and hyperthermia on the AS-48 release from the nano-formulation was also studied. These results show a slower AS-48 release from PLGA[AS-48-BMNPs] compared to previous nano-formulations, which could make this new nano-formulation suitable for longer extended treatments of intracellular pathogens. PLGA[AS-48-BMNPs] are internalized in THP-1 cells where AS-48 is liberated slowly, which may be useful to treat diseases and prevent infection caused by intracellular pathogens. The treatment will be more efficient combined with hyperthermia or photothermia.

Cell membrane-coated biomimetic magnetic nanoparticles for the bio-specific extraction of components from Gualou Guizhi decoction exhibiting activities against oxygen-glucose deprivation/reperfusion injury

Gua-Lou-Gui-Zhi decoction (GLGZD) is a classical multiherb traditional Chinese medicine formula that has ameliorative effects on oxygen-glucose deprivation/reperfusion (OGD/R) injury and has been applied for the treatment of stroke in clinical practice; however, its active ingredients remain unknown. The aim of this study was to develop an effective method for screening for components of GLGZD with potential therapeutic activity against OGD/R injury. Brain microvascular endothelial cell membrane-coated magnetic beads (CMs@rBMECs-MBs) were incubated with the GLGZD extract; the bound material was eluted and the constituents were identified using solid phase extraction and ultra-performance liquid chromatography-Orbitrap Fusion Tribrid mass spectrometry (UPLC-Orbitrap Fusion Tribrid MS). The biological activities of the identified GLGZD components were analyzed using OGD/R-exposed brain endothelial cells. Seven compounds bound to the CMs@rBMECs-MBs were identified as gallic acid, paeoniflorin, liquiritigenin, isoliquiritigenin, liquiritin, isoliquiritin, and formononetin. Among them, six (except formononetin) protected brain endothelial cells against OGD/R injury in a concentration-dependent manner (20–120 μM; P < 0.01–0.05) and downregulated the expression of hypoxia-inducible factor-1α (P < 0.01) involved in the pathogenic mechanisms triggered by stroke. Our findings suggest that the screening of bioactive compounds using cell membrane-coated magnetic beads combined with solid phase extraction and UPLC-Orbitrap Fusion Tribrid MS is an effective method for the bio-specific extraction and identification of ingredients responsible for the therapeutic activity of traditional Chinese medicines.

Antibacterial directed chemotherapy using AS-48 peptide immobilized on biomimetic magnetic nanoparticles combined with magnetic hyperthermia

The design of new strategies to increase the effectiveness of the antibacterial treatments is a main goal in public health. So, the aim of the study was to achieve a local antibacterial directed therapy as novel alternative allowing both, the delivery of the drug at the target, while minimizing undesirable side effects, thus anticipating an enhanced effectiveness. Hence, we have developed an innovative nanoformulation composed by biomimetic magnetic nanoparticles functionalized with the antimicrobial peptide AS-48 and its potential against Gram-positive and Gram-negative bacteria, either by itself or combined with magnetic hyperthermia has been investigated. Besides, the physical properties, binding efficiency, stability and mechanism of action of this nanoassembly are analyzed. Remarkably, the nanoassembly has a strong bactericidal effect on Gram-positive bacteria, but surprisingly also on E. coli and, finally, when combined with magnetic hyperthermia, on P. aeruginosa and K. pneumoniae. The results obtained represent a breakthrough since it allows a local treatment of infections, reducing and concentrating the dose of antimicrobial compounds, avoiding secondary effects, including the resistance generation and particularly because the combination with magnetic hyperthermia helps sensitizing resistant bacteria to the bactericidal effect of AS-48. Thus, this new formulation should be considered a promising tool in the antibacterial fight.

Enhanced Cytotoxic Effect of TAT-PLGA-Embedded DOXO Carried by Biomimetic Magnetic Nanoparticles upon Combination with Magnetic Hyperthermia and Photothermia.

The synergy between directed chemotherapy and thermal therapy (both magnetic hyperthermia and photothermia) mediated by a nanoassembly composed of functionalized biomimetic magnetic nanoparticles (BMNPs) with the chemotherapeutic drug doxorubicin (DOXO) covered by the polymer poly(lactic-co-glycolic acid) (PLGA), decorated with TAT peptide (here referred to as TAT–PLGA(DOXO-BMNPs)) is explored in the present study. The rationale behind this nanoassembly lies in an optimization of the nanoformulation DOXO-BMNPs, already demonstrated to be more efficient against tumor cells, both in vitro and in vivo, than systemic traditional therapies. By embedding DOXO-BMNPs into PLGA, which is further functionalized with the cell-penetrating TAT peptide, the resulting nanoassembly is able to mediate drug transport (using DOXO as a drug model) and behaves as a hyperthermic agent (induced by an alternating magnetic field (AMF) or by laser irradiation with a laser power density of 2 W/cm2). Our results obtained using the HepG2 cell line show that there is a synergy between chemotherapy and thermal therapy that results in a stronger cytotoxic effect when compared to that caused by the soluble DOXO. This is probably due to the enhanced DOXO release occurring upon the application of the thermal therapy, as well as the induced local temperature rise mediated by BMNPs in the nanoassembly following exposition to AMF or to near-infrared (NIR) laser irradiation. These results represent a proof of concept demonstrating that TAT–PLGA(DOXO-BMNPs) can be used to efficiently combine therapies against tumor cells, which is a step forward in the transition from systemic to local treatments.

Inside-Out-Oriented Cell Membrane Biomimetic Magnetic Nanoparticles for High-Performance Drug Lead Discovery.

Biomimetic cell membrane-coated nanoparticles have been broadly applied because of their superior biochemical properties. The right-side-out cell membrane coating manner provides nanoparticles with an immune-evasive stealth function in vivo. However, this acts as a drag for drug discovery when the drug targets are the intracellular domain of transmembrane receptors. Herein, inside-out-oriented cell membrane-coated nanoparticles were prepared for screening tyrosine kinase inhibitors, which specifically interacted with the intracellular kinase domain of the epidermal growth factor receptor. Biotinylated human lung adenocarcinoma epithelial cell membranes specifically interacted with streptavidin-immobilized Fe3O4 magnetic nanoparticles and then formed inside-out-oriented cell membrane-coated magnetic nanoparticles (IOCMMNPs). The cell membrane orientation of the IOCMMNPs was successfully confirmed by immunogold electron microscopy, fluorescently labeled confocal microscopy, sialic acid quantification assay, and the adsorption capacity assay. Moreover, IOCMMNPs possessed satisfactory binding capacity, selectivity, and high sensitivity (limit of detection = 0.4 × 10-3 μg mL-1). Ultimately, IOCMMNPs successfully targeted two main compounds from Strychnos nux-vomica whose potential antitumor activities were further validated by pharmacological studies. The application of the inside-out cell membrane coating strategy further enhances the drug screening efficiency and broadens the insight and methodologies for drug lead discovery. This inside-out cell membrane coating concept also provides a method for the future development of engineered cell membrane-coated nanotechnology.

Synergistic Photothermal-Chemotherapy Based on the Use of Biomimetic Magnetic Nanoparticles.

MamC-mediated biomimetic magnetic nanoparticles (BMNPs) have emerged as one of the most promising nanomaterials due to their magnetic features (superparamagnetic character and large magnetic moment per particle), their novel surface properties determined by MamC, their biocompatibility and their ability as magnetic hyperthermia agents. However, the current clinical application of magnetic hyperthermia is limited due to the fact that, in order to be able to reach an effective temperature at the target site, relatively high nanoparticle concentration, as well as high magnetic field strength and/or AC frequency are needed. In the present study, the potential of BMNPs to increase the temperature upon irradiation of a laser beam in the near infrared, at a wavelength at which tissues become partially transparent, is explored. Moreover, our results also demonstrate the synergy between photothermia and chemotherapy in terms of drug release and cytotoxicity, by using BMNPs functionalized with doxorubicin, and the effectiveness of this combination therapy against tumor cells in in vitro experiments. Therefore, the findings of the present study open the possibility of a novel, alternative approach to fight localized tumors.

Improving the Cellular Uptake of Biomimetic Magnetic Nanoparticles.

Magnetococcus marinus magnetosome-associated protein MamC, expressed as recombinant, has been proven to mediate the formation of novel biomimetic magnetic nanoparticles (BMNPs) that are successful drug nanocarriers for targeted chemotherapy and hyperthermia agents. These BMNPs present several advantages over inorganic magnetic nanoparticles, such as larger sizes that allow the former to have larger magnetic moment per particle, and an isoelectric point at acidic pH values, which allows both the stable functionalization of BMNPs at physiological pH value and the molecule release at acidic (tumor) environments, simply based on electrostatic interactions. However, difficulties for BMNPs cell internalization still hold back the efficiency of these nanoparticles as drug nanocarriers and hyperthermia agents. In the present study we explore the enhanced BMNPs internalization following upon their encapsulation by poly (lactic-co-glycolic) acid (PLGA), a Food and Drug Administration (FDA) approved molecule. Internalization is further optimized by the functionalization of the nanoformulation with the cell-penetrating TAT peptide (TATp). Our results evidence that cells treated with the nanoformulation [TAT-PLGA(BMNPs)] show up to 80% more iron internalized (after 72 h) compared to that of cells treated with BMNPs (40%), without any significant decrease in cell viability. This nanoformulation showing optimal internalization is further characterized. In particular, the present manuscript demonstrates that neither its magnetic properties nor its performance as a hyperthermia agent are significantly altered due to the encapsulation. In vitro experiments demonstrate that, following upon the application of an alternating magnetic field on U87MG cells treated with BMNPs and TAT-PLGA(BMNPs), the cytotoxic effect of BMNPs was not affected by the TAT-PLGA enveloping. Based on that, difficulties shown in previous studies related to poor cell uptake of BMNPs can be overcome by the novel nanoassembly described here.

Enzyme Storage and Recycling: Nanoassemblies of α-Amylase and Xylanase Immobilized on Biomimetic Magnetic Nanoparticles.

Immobilization of enzymes has been extensively required in a wide variety of industrial applications as a way to ensure functionality and the potential of enzyme recycling after use. In particular, enzyme immobilization on magnetic nanoparticles (MNPs) could offer reusability by means of magnetic recovery and concentration, along with increased stability and robust activity of the enzyme under different physicochemical conditions. In the present work, microbial α-amylase (AmyKS) and xylanase (XAn11) were both immobilized on different types of MNPs [MamC-mediated biomimetic MNPs (BMNPs) and inorganic MNPs] by using two different strategies (electrostatic interaction and covalent bond). AmyKS immobilization was successful using electrostatic interaction with BMNPs. Instead, the best strategy to immobilize XAn11 was using MNPs through the hetero-crosslinker 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The immobilization protocols were optimized by varying glutaraldehyde (GA) concentration, enzyme quantity, and reaction time. Under optimal conditions, 92% of AmyKS and 87% of XAn11 were immobilized on BMNPs and MNPs–E/N, respectively (here referred as AmyKS–BMNPs and XAn11–MNPs nanoassemblies). The results show that the immobilization of the enzymes did not extensively alter their functionality and increased enzyme stability compared to that of the free enzyme upon storage at 4 and 20 °C. Interestingly, the immobilized amylase and xylanase were reused for 15 and 8 cycles, respectively, without significant loss of activity upon magnetic recovery of the nanoassemblies. The results suggest the great potential of these nanoassemblies in bioindustry applications.

Cell membrane-encapsulated magnetic nanoparticles for enhancing natural killer cell-mediated cancer immunotherapy

Natural killer (NK) cells have exhibited therapeutic potential for various malignant tumors. However, the cytotoxic effect of NK cells is relatively weak and less specific compared to other immunotherapy approaches such as chimeric antigen receptor T-Cell (CART) therapy, constituting a great challenge for adoptive immunotherapy. Here, we report cell membrane-encapsulated magnetic nanoparticles for activating NK cells and enhancing anti-tumor effects. Magnetic nanoparticles were coated with silicon dioxide (SiO2), and cancer cell membranes were mixed with Fe3O4@SiO2 to construct cancer cell membrane coated Fe3O4@SiO2 magnetic nanoparticles (CMNPs). The functionalized nanoparticles bearing cancer-specific antigens on the surface effectively stimulated NK cells by enhancing expression of surface activating receptors and boosting anti-tumor function through the secretion of soluble cytotoxic effectors. To conclude, the biomimetic magnetic nanoparticles offer a versatile and powerful tool to present tumor-specific antigens, priming anti-tumor capability, which is promising to enhance NK cell-based adoptive cancer immunotherapy.

Nanoformulation Design Including MamC-Mediated Biomimetic Nanoparticles Allows the Simultaneous Application of Targeted Drug Delivery and Magnetic Hyperthermia.

The design of novel nanomaterials that can be used as multifunctional platforms allowing the combination of therapies is gaining increased interest. Moreover, if this nanomaterial is intended for a targeted drug delivery, the use of several guidance methods to increase guidance efficiency is also crucial. Magnetic nanoparticles (MNPs) allow this combination of therapies and guidance strategies. In fact, MNPs can be used simultaneously as drug nanocarriers and magnetic hyperthermia agents and, moreover, they can be guided toward the target by an external magnetic field and by their functionalization with a specific probe. However, it is difficult to find a system based on MNPs that exhibits optimal conditions as a drug nanocarrier and as a magnetic hyperthermia agent. In this work, a novel nanoformulation is proposed to be used as a multifunctional platform that also allows dual complementary guidance. This nanoformulation is based on mixtures of inorganic magnetic nanoparticles (M) that have been shown to be optimal hyperthermia agents, and biomimetic magnetic nanoparticles (BM), that have been shown to be highly efficient drug nanocarriers. The presence of the magnetosome protein MamC at the surface of BM confers novel surface properties that allow for the efficient and stable functionalization of these nanoparticles without the need of further coating, with the release of the relevant molecule being pH-dependent, improved by magnetic hyperthermia. The BM are functionalized with Doxorubicin (DOXO) as a model drug and with an antibody that allows for dual guidance based on a magnetic field and on an antibody. The present study represents a proof of concept to optimize the nanoformulation composition in order to provide the best performance in terms of the magnetic hyperthermia agent and drug nanocarrier.

Biomimetic Magnetoliposomes as Oxaliplatin Nanocarriers: In Vitro Study for Potential Application in Colon Cancer.

Current chemotherapy for colorectal cancer (CRC) includes the use of oxaliplatin (Oxa), a first-line cytotoxic drug which, in combination with irinotecan/5-fluorouracil or biologic agents, increases the survival rate of patients. However, the administration of this drug induces side effects that limit its application in patients, making it necessary to develop new tools for targeted chemotherapy. MamC-mediated biomimetic magnetic nanoparticles coupled with Oxa (Oxa-BMNPs) have been previously demonstrated to efficiently reduce the IC50 compared to that of soluble Oxa. However, their strong interaction with the macrophages revealed toxicity and possibility of aggregation. In this scenario, a further improvement of this nanoassembly was necessary. In the present study, Oxa-BMNPs nanoassemblies were enveloped in phosphatidylcholine unilamellar liposomes (both pegylated and non-pegylated). Our results demonstrate that the addition of both a lipid cover and further pegylation improves the biocompatibility and cellular uptake of the Oxa-BMNPs nanoassemblies without significantly reducing their cytotoxic activity in colon cancer cells. In particular, with the pegylated magnetoliposome nanoformulation (a) hemolysis was reduced from 5% to 2%, being now hematocompatibles, (b) red blood cell agglutination was reduced, (c) toxicity in white blood cells was eliminated. This study represents a truly stepforward in this area as describes the production of one of the very few existing nanoformulations that could be used for a local chemotherapy to treat CRC.

Platelet Membrane-Camouflaged Magnetic Nanoparticles for Ferroptosis-Enhanced Cancer Immunotherapy.

Although cancer immunotherapy has emerged as a tremendously promising cancer therapy method, it remains effective only for several cancers. Photoimmunotherapy (e.g., photodynamic/photothermal therapy) could synergistically enhance the immune response of immunotherapy. However, excessively generated immunogenicity will cause serious inflammatory response syndrome. Herein, biomimetic magnetic nanoparticles, Fe3 O4 -SAS @ PLT, are reported as a novel approach to sensitize effective ferroptosis and generate mild immunogenicity, enhancing the response rate of non-inflamed tumors for cancer immunotherapy. Fe3 O4 -SAS@PLT are built from sulfasalazine (SAS)-loaded mesoporous magnetic nanoparticles (Fe3 O4 ) and platelet (PLT) membrane camouflage and triggered a ferroptotic cell death via inhibiting the glutamate-cystine antiporter system Xc- pathway. Fe3 O4 -SAS @ PLT-mediated ferroptosis significantly improves the efficacy of programmed cell death 1 immune checkpoint blockade therapy and achieves a continuous tumor elimination in a mouse model of 4T1 metastatic tumors. Proteomics studies reveal that Fe3 O4 -SAS @ PLT-mediated ferroptosis could not only induce tumor-specific immune response but also efficiently repolarize macrophages from immunosuppressive M2 phenotype to antitumor M1 phenotype. Therefore, the concomitant of Fe3 O4 -SAS @ PLT-mediated ferroptosis with immunotherapy are expected to provide great potential in the clinical treatment of tumor metastasis.

Surface Molecularly Imprinted Biomimetic Magnetic Nanoparticles for Enantioseparation

A cost-effective and robust biomimetic magnetic nanomaterial based on surface molecular imprinting similar to antibody-like biorecognition sites for chiral drug molecules has been demonstrated. The...