Magnetic Liposomes Research Articles

Comparative In Vitro Study between Biocompatible Chitosan-Based Magnetic Nanocapsules and Liposome Formulations with Potential Application in Anti-Inflammatory Therapy.

This study describes the comparison between the interaction of a series of peptide-functionalized chitosan-based nanocapsules and liposomes with two cell lines, i.e., mouse macrophages RAW 264.7 and human endothelial cells EA.hy926. Both types of nanocarriers are loaded with magnetic nanoparticles and designed for anti-inflammatory therapy. The choice of these magnetic nanostructures is argued based on their advantages in terms of size, morphology, chemical composition, and the multiple possibilities of modifying their surface. Moreover, active targeting might be ensured by using an external magnetic field. To explore the impact of chitosan-based nanocapsules and liposomes on cell cytophysiology, the cell viability, using the MTT assay, and cell morphology were investigated. The results revealed low to moderate cytotoxicity of free nanocapsules and significant cytotoxicity induced by chitosan-coated liposomes loaded with dexamethasone, confirming its release from the delivery system. Thus, after 48 h of treatment with nanocapsules, the viability of RAW 264.7 cells varied between 88.18% (OCNPM-1I, 3.125 µg/mL) and 76.37% (OCNPM-1, 25 µg/mL). In the same conditions, EA.hy926 cell viability was between 99.91% (OCNPM-3, 3.125 µg/mL) and 75.15% (OCNPM-3, 25 µg/mL) at the highest dose (25 µg/mL), the values being comparable for both cell lines. Referring to the cell reactivity after dexamethasone-loaded liposome application, the lowest viability of RAW 264.7 cells was 41.25% (CLDM5CP-1, 25 µg/mL) and 58.20% (CLDMM2CP-1 1.25 µg/mL) in the endothelial cell line, proving a selective character of action of nanocarriers. The cell morphology test, performed to support and confirm the results obtained by the MTT test, revealed a differentiated response for the two types of nano-carriers. As expected, an intense cytotoxic effect in the case of dexamethasone-loaded liposomes and a lack of cytotoxicity for drug-free nanocapsules were noticed. Therefore, our study demonstrated the biocompatible feature of the studied nanocarriers, which highlights them for future research as potential drug delivery systems for pharmacological applications, including anti-inflammatory therapy.

Construction strategy of stimuli-responsive liposome and its biological application

Stimuli-responsive liposomes, a novel type of nanocarriers, have been widely used in the fields of medicine, food, and cosmetics. This paper provides a comprehensive introduction to the preparation methods, construction strategies, and biological applications of stimuli-responsive liposomes. The review highlights the functional principles of pH-sensitive, redox-sensitive, enzyme-sensitive, heat-sensitive, light-sensitive, and magnetic field-responsive liposomes, and summarizes their applications based on various drug delivery mode. Finally, the article provides an overview of the current challenges and future development prospects for stimuli-responsive liposomes.

Preparation of a Novel Multifunctional Cationic Liposome Drug-carrying System and its Functional Study on Lung Cancer.

Low-dose chemotherapy is a promising treatment strategy that may be improved by controlled delivery. This study aimed to design polyethylene glycol-stabilized bilayer-decorated magnetic Cationic Liposomes (CLs) as a drug delivery system for integrated functional studies of lung cancer cell therapy and imaging. A novel multifunctional folic acid targeting magnetic CLs docetaxel drug-loading system (FA-CLs-Fe- DOC) was prepared and tested for its physical properties, encapsulation rate and drug release performance. The feasibility of FA-CLs-Fe-DOC ability to inhibit tumor cells and act as an MRI contrast agent was investigated in vitro, and the target recognition and therapeutic ability of FA-CLs-Fe-DOC was studied in vivo. FA-CLs-Fe-DOC had a particle size of 221.54 ± 6.42 nm and a potential of 28.64 ± 3.56 mv, with superparamagnetic properties and better stability. The encapsulation rate was 95.36 ± 1.63%, and the drug loading capacity was 9.52 ± 0.22%, which possessed the drug slow-release performance and low cytotoxicity and could effectively inhibit the proliferation of lung cancer cells, promoting apoptosis of lung cancer cells. MRI showed that it had the function of tracking and localization of lung cancer cells. In vivo experiments confirmed the targeted recognition property and therapeutic function of lung cancer cells. In this study, we successfully prepared an FA-CLs-Fe-DOC capable of specifically targeting lung cancer cells with integrated functions of efficient lung cancer cell killing and imaging localization. This targeted drug packaging technology may provide a new strategy for the design of integrated carriers for targeted cancer therapy and imaging.

Inhibitory Effect of Iron Oxide Nanoparticle Liposome on the Growth of Non-Small Cell Lung Cancer In Vitro

In this study, we assessed the inhibitory potential of magnetic liposomes as gene vectors targeting human non-small cell lung cancer (NSCLC) growth In Vitro via hairpin RNA (shRNA) under the influence of an external magnetic field. Specifically, we engineered the plasmid pGFPshIGF-1R to co-express green fluorescent protein (GFP) and shRNA against insulin-like growth factor-1 receptor (IGF-1R), a gene associated with NSCLC progression. Utilizing superparamagnetic iron oxide nanoparticles (CombiMAG) and Lipofectamine2000,we constructed magnetic liposomes to deliver pGFPshIGF-1R into A549 NSCLC cells. Varying magnetic field strengths and exposure times were employed. The efficacy of transfection was gauged against liposome-only methods using Western blot analysis to measure IGF-1R protein reduction. In Vitro, the magnetic approach exhibited higher transfection efficiency (66.3%) compared to liposomes alone (22.1%), marking a threefold enhancement. In vivo, using a subcutaneous A549 tumor model in nude mice, shRNA-transfected A549 cells displayed substantial IGF-1R protein inhibition (interference rates: 56.1% and 85.1%). Importantly, magnetic transfection outperformed liposomal transfection in suppressing IGF-1R protein expression (P <0.05). Our findings suggest that magnetic liposome-mediated gene delivery, facilitated by an external magnetic field, holds promise as a targeted and safe therapeutic strategy for lung cancer.

Magnetic Delivery of Antigen‐Loaded Magnetic Liposomes for Active Lymph Node Targeting and Enhanced Anti‐Tumor Immunity (Adv. Healthcare Mater. 32/2023)

Magnetic Delivery of Antigen‐Loaded Magnetic Liposomes for Active Lymph Node Targeting and Enhanced Anti‐Tumor Immunity (Adv. Healthcare Mater. 32/2023)

Quercetin‐encapsulated magnetoliposomes: Fabrication, optimization, characterization, and antioxidant studies

AbstractQuercetin (QU) faces challenges in its therapeutic efficacy due to its hydrophobic nature and limited oral bioavailability. Using a Box–Behnken design (BBD) approach, we developed QU‐loaded magnetoliposomes (QMLs) to address these limitations. By encapsulating QU within iron oxide nanoparticles (IONPs) and liposomes (LPs), we enhanced its hydrophilicity and improved its potential for drug delivery. Through systematic adjustments of phosal, polyvinyl alcohol, and magnetic/IONPs, we optimized the particle size, zeta potential, and iron content of the QMLs. The formulations underwent comprehensive structural characterization using techniques, such as Fourier transform infrared spectroscopy, X‐Ray diffraction, differential scanning calorimetry–thermogravimetric analysis, and energy‐dispersive X‐ray analysis, whereas their morphology was examined through field emission scanning electron microscopy. Furthermore, we evaluated the in vitro drug release of the QMLs and antioxidant activity of QU, QU‐loaded LPs, and QMLs using DPPH, 2,2′‐azino‐bis(3‐ethylbenzthiazoline‐6‐sulfonic acid), and H2O2 scavenging assays, enabling us to compare their antioxidant potential and the efficiency of QU encapsulation within the magneto LPs.Practical Applications: This research holds significant practical implications, particularly in targeted drug delivery using magnetic liposomes. The developed system shows promise in enhancing cancer therapy, providing localized treatment for inflammation‐related conditions, delivering drugs to the brain to address neurological disorders, promoting wound healing, and incorporating quercetin into skincare products for its antioxidant and antiaging benefits.

Magnetic Delivery of Antigen-Loaded Magnetic Liposomes for Active Lymph Node Targeting and Enhanced Anti-Tumor Immunity.

Therapeutic cancer vaccines offer the greatest advantage of enhancing antigen-specific immunity against tumors, particularly for immunogenic tumors, such as melanoma. However, clinical responses remain unsatisfactory, primarily due to inadequate T cell priming and the development of acquired immune tolerance. A major obstacle lies in the inefficient uptake of antigen by peripheral dendritic cells (DCs) and their migration to lymph nodes for antigen presentation. In this context, the magnetic delivery of antigen-loaded magnetic liposomes (Ag-MLs) to actively target lymph node, is proposed. These magnetic responsive liposomes contain soluble mouse melanoma lysate and iron oxide nanoparticles in the core, along with the immunostimulatory adjuvant CpG-1826 incorporated into the lipid bilayer. When applied through magnetic targeting in the mouse melanoma model, Ag-MLs accumulate significantly in the target lymph nodes. This accumulation results in increased population of active DCs in lymph nodes and cytotoxic T lymphocytes (CTLs) within tumors, correlating with effective tumor growth inhibition. Overall, this study demonstrates the potential of magnetic targeting as an effective strategy for delivering cancer vaccines and activating the immune response, offering a novel platform for cancer immunotherapies.

Magnetic Liposomes Infused with GPCR-Expressing Cell Membrane for Targeted Extraction Using Minimum Organic Solvent: An Investigative Study of Trace THC in Sewage.

Trace analysis of lipophilic substances in complex environmental, food, or biological matrices has proven to be a challenge, on account of their high susceptibility to adsorption by particulate matter and liquid-solid interfaces. For this purpose, liquid-liquid extraction (LLE) is often employed as the separation method, which uses water-immiscible organic solvents. As an alternative, magnetic solid-phase extraction (MSPE) allows for adsorption, separation, and recovery of analytes from large volumes of aqueous samples with minimum usage of organic solvents. However, the poor selectivity hampers its performance in various scenarios, especially in sewage samples where complicated and unpredictable interference exists, resulting in block of the active adsorption sites of the sorbent. To this end, we propose receptor-affinity MSPE employing magnetic liposomes decorated with cell membranes expressing G-protein-coupled receptor as the sorbents. Application of the novel sorbent CM@Lip@Fe infused with CB1 cannabinoid receptors was demonstrated for the targeted extraction and enrichment of tetrahydrocannabinol from sewage matrix. Thanks to the high affinity and molecular selectivity of the ligand-receptor interactions, a limit of quantitation of 5.17 ng/L was achieved coupled with HPLC-MS/MS in unfiltered raw sewage, featuring minimum usage of organic solvents, fivefold enhanced sensitivity, low sorbent dosage (75 mg/L of sewage), and high efficiency as major advantages over conventional LLE. This work establishes a framework for efficient separation of specific molecules from complex media, thus promising to extend and refine standard LLE as the clean-up procedure for trace analysis.

A Moexitecan Magnetic Liposomal Strategy for Ferroptosis-Enhanced Chemotherapy.

Moexitecan (Mex) is a novel camptothecin derivative that retains the potent antitumor properties of camptothecin drugs and has improved hydrophilicity to enhance biocompatibility in vitro. However, single-drug therapy still has limitations. In this study, magnetic liposomes loaded with both moexitecan and superparamagnetic iron oxide nanoparticles (SPIO) have been fabricated by a film hydration and filtration method, which is abbreviated as Mex@MLipo. By using liposomes as drug carriers, Mex can be delivered specifically to the target site, resulting in improved therapeutic efficacy and reduced toxicity. Morphology characterization results show that Mex@MLipo has a mean diameter of 180-200 nm with a round morphology. The loading efficiencies of Mex and SPIO are 65.86% and 76.86%, respectively. Cell toxicity, in vitro cell uptake, and in vivo fluorescence imaging experiments showed that Mex@MLipo was the most effective in killing HT-29 cells compared with HepG-2 and PC-3 cells, due to its ability to combine chemotherapy and induce ferroptosis, resulting in a strong anti-tumor effect. Thus, this study developed an innovative nanoscale drug delivery system that paves the way for clinical applications of moexitecan.

Development of doxorubicin-encapsulated magnetic liposome@PEG for treatment of breast cancer in BALB/c mice.

The magnetic doxorubicin-encapsulated liposome/PEG/Fe3O4 (called as DOX@m-Lip/PEG) was synthesized and studied as a novel nanocarrier for the treatment of breast cancer in BALB/c mice. Nanocarrier was characterized by FT-IR, zeta-potential sizer, EDX elemental analysis, EDX mapping, TEM, and DLS techniques. The results showed that the size of the nanocarrier was determined around 128nm by TEM. EDX study confirmed PEG-conjugation in the magnetic liposomes and was homogenously distributed in the nanosize range (100-200nm) with a negative surface charge (-61.7mV). The kinetic studies indicated that the release of doxorubicin from DOX@m-Lip/PEG follows the Korsmeyer-Peppas model. The n-value of the model was 0.315, indicating that doxorubicin release from the nanocarrier had a slow releasing rate and followed Fick's law. The DOX release from the nanocarrier lasted a long time (more than 300h). In in vivo part, a mouse 4T1 breast tumor model was used. The in vivo results indicated that DOX@m-Lip/PEG caused much stronger tumor cell necrosis and less cardiotoxic effects than the other groups. In conclusion, we show that m-Lip/PEG is a promising nanocarrier for low dosage and slow release of doxorubicin in treating breast cancer, and treatment with encapsulated DOX (DOX@m-Lip/PEG) demonstrated higher efficacy with low cardiac toxicity. Besides, the magnetic property of m-Lip@PEG nanocarrier allows it to be a potent mater for hyperthermia and MRI studies.

Thermosensitive Cationic Magnetic Liposomes for Thermoresponsive Delivery of CPT-11 and SLP2 shRNA in Glioblastoma Treatment.

Thermosensitive cationic magnetic liposomes (TCMLs), prepared from dipalmitoylphosphatidylcholine (DPPC), cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)]-2000, and didodecyldimethylammonium bromide (DDAB) were used in this study for the controlled release of drug/gene for cancer treatment. After co-entrapping citric-acid-coated magnetic nanoparticles (MNPs) and the chemotherapeutic drug irinotecan (CPT-11) in the core of TCML (TCML@CPT-11), SLP2 shRNA plasmids were complexed with DDAB in the lipid bilayer to prepare TCML@CPT-11/shRNA with a 135.6 ± 2.1 nm diameter. As DPPC has a melting temperature slightly above the physiological temperature, drug release from the liposomes can be triggered by an increase in solution temperature or by magneto-heating induced with an alternating magnetic field (AMF). The MNPs in the liposomes also endow the TCMLs with magnetically targeted drug delivery with guidance by a magnetic field. The successful preparation of drug-loaded liposomes was confirmed by various physical and chemical methods. Enhanced drug release, from 18% to 59%, at pH 7.4 was observed when raising the temperature from 37 to 43 °C, as well as during induction with an AMF. The in vitro cell culture experiments endorse the biocompatibility of TCMLs, whereas TCML@CPT-11 shows some enhancement of cytotoxicity toward U87 human glioblastoma cells when compared with free CPT-11. The U87 cells can be transfected with the SLP2 shRNA plasmids with very high efficiency (~100%), leading to silencing of the SLP2 gene and reducing the migration ability of U87 from 63% to 24% in a wound-healing assay. Finally, an in vivo study, using subcutaneously implanted U87 xenografts in nude mice, demonstrates that the intravenous injection of TCML@CPT11-shRNA, plus magnetic guidance and AMF treatment, can provide a safe and promising therapeutic modality for glioblastoma treatment.

Efficient Liposome Loading onto Surface of Mesenchymal Stem Cells via Electrostatic Interactions for Tumor-Targeted Drug Delivery.

Mesenchymal stem cells (MSCs) have a tumor-homing capacity; therefore, MSCs are a promising drug delivery carrier for cancer therapy. To maintain the viability and activity of MSCs, anti-cancer drugs are preferably loaded on the surface of MSCs, rather than directly introduced into MSCs. In this study, we attempted to load liposomes on the surface of MSCs by using the magnetic anionic liposome/atelocollagen complexes that we previously developed and assessed the characters of liposome-loaded MSCs as drug carriers. We observed that large-sized magnetic anionic liposome/atelocollagen complexes were abundantly associated with MSCs via electrostatic interactions under a magnetic field, and its cellular internalization was lower than that of the small-sized complexes. Moreover, the complexes with higher atelocollagen concentrations showed lower cellular internalization than the complexes with lower atelocollagen concentrations. Based on these results, we succeeded in the efficient loading of liposomes on the surface of MSCs by using large-sized magnetic anionic liposomes complexed with a high concentration of atelocollagen. The constructed liposome-loaded MSCs showed a comparable proliferation rate and differentiation potential to non-loaded MSCs. Furthermore, the liposome-loaded MSCs efficiently adhered to vascular endothelial cells and migrated toward the conditioned medium from cancer cells in vitro and solid tumor tissue in vivo. These findings suggest that liposome-loaded MSCs could serve as an efficient cell-based drug carrier for tumor-targeted delivery.

Magnetic liposome as a dual-targeting delivery system for idiopathic pulmonary fibrosis treatment

Idiopathic pulmonary fibrosis (IPF) is the most common form of idiopathic interstitial pneumonia, where M2 macrophages play an irreplaceable role in the anti-inflammatory progress. Targeting M2 macrophages and regulating their polarization may be a potential treatment strategy for IPF. Herein, we designed a magnetic liposome based dual-targeting delivery system for the IPF treatment, constructed by mannose-modified magnetic nanoparticles (MAN-MNPs) loaded on the surface of the liposome (MAN-MNPs@LP). The delivery system is capable of responding to a static magnetic field (SMF) and then recognizing in situ of M2 macrophages through the mannose receptor-dependent internalization. Firstly, a series of physical and chemical assays were used to characterize these nanoparticles. Subsequently, magnetic liposomes accumulation in the damaged lung with/without mannose modification and SMF were compared by in vivo imaging system. Finally, the reduction of M2 macrophages and inhibition of their polarization confirmed that the development of IPF was retarded due to the in situ release of encapsulated dexamethasone (Dex) in lungs under the SMF. Further investigation demonstrated that the expression of α-SMA and collagen deposition was reduced. Altogether, this dual-targeting delivery system can effectively deliver Dex into M2 macrophages in the lung, making it a novel and promising therapeutic system for the IPF treatment.

GLUT1-mediated magnetic liposomes for targeting bone metastatic breast cancer

Bone metastatic breast cancer is a malignant tumor in bone due to the metastasis of breast cancer, and its incidence is increasing worldwide. Treatment of cancer metastasized to bone is still a challenge because of the anticancer drugs lack target specificity. Finding an effective treatment for bone metastasis remains an urgent issue. In order to enhance the delivery of paclitaxel (PTX) to the bone metastases lesions, a novel glucose derivative was designed and synthesized in this work, which was used as liposome ligand to develop the magnetic liposome G-MLip (Glucose-modified magnetic liposome). The liposome could improve the drug formulations in the bone metastases mediated by glucose transporter 1 (GLUT1) and then target cancer cells. The PTX-loaded magnetic liposome PTX-G-MLip was prepared by the film hydration-ultrasound method. And the characterizations, such as size, zeta potential, encapsulation efficiency, release profile, stability, hemolysis, were well evaluated. What’s more, the enhanced target ability was also investigated in vitro and in mice. The metastatic bone-targeted capacity was confirmed that the PTX concentration from PTX-G-MLip in the bone metastases lesions was markedly increased in the presence of magnetic field (MF) compared with the free PTX and other liposomes. Inspired by the enhanced targeting ability, glucose-modified magnetic liposomes could serve as an effective drug delivery system for targeting and treating bone metastases.

Magnetic Thermosensitive Liposomes Loaded with Doxorubicin.

Liposome-mediated anticancer drug delivery has the advantage of limiting the massive cytotoxicity of chemotherapeutic agents. Doxorubicin (DOX) PEG-liposomal does however have a slow-release rate that hinders its therapeutic efficacy. In this study, an integrated therapeutic system based on magnetic thermosensitive liposomes was designed. The chelated gadolinium acquired magnetic properties in the liposomes. The hyperthermia induced by ultra-high-field magnetic resonance imaging (UHF-MRI) enhances the chemotherapeutic effects of DOX. The DOX release from liposomes was facilitated over a narrow range of temperatures owing to the phase transition temperature of the liposomes. The magnetic properties of the liposomes were evident by the elevation of contrast after the exposure to UHF-MRI. Moreover, triple-negative breast cancer (TNBC) cells showed a significant decrease in cellular viability reaching less than 40% viability after 1h of exposure to UHF-MRI. The liposomes demonstrated a physiological coagulation time and a minimal hemolytic potential in hemocompatibility studies; therefore, they were considered safe for physiological application. As a result, magnetic-thermosensitive liposomal guidance of local delivery of DOX could increase the therapeutic index, thereby reducing the amount of the drug required for systemic administration and the chance of affecting the adjacent tissues.

Magnetorheological liposomes. An alternative approach for drug delivery driven by mutual magnetic dipole–dipole interaction

In this study consideration is given to an alternative approach for drug release by the use magnetorheological liposomes with the aim to eliminate the need for an external oscillatory magnetic field (hyperthermia) for rupture of the liposome. Contrariwise traditional magnetic liposomes – using nano magnetic particles or ferrofluids, here the magnetic liposome contains a magnetorheological particle (i.e., of micrometric size) which makes the dipole–dipole magnetic interaction between particles strong enough to break up the bilipid layer and then releasing the drug. Utilizing a simplified physical model an expression for the liposome rupture by dipole–dipole magnetic interaction as a function of the drug and magnetorheological particle fraction was derived. It is shown that rupture of the bilipid layer by dipole–dipole magnetic interaction could be feasible when the magnetorheological particle fraction inside the liposome is around a 20 per cent or higher.

Preparation of Magnetized Mesenchymal Stem Cells Using Magnetic Liposomes to Enhance Their Retention in Targeted Tissue -Evaluation of Retention and Anti-inflammatory Efficiency in Skeletal Muscle

Magnetic nanoparticle-incorporated liposomes (magnetic liposomes) are considered a promising site-specific drug delivery carrier. Although there are many reports on the development of magnetic liposomes, most of them focus on the characteristics of magnetic nanoparticles, rather than liposomes. Therefore, we first evaluated the effect of the physicochemical properties of magnetic liposomes on their interaction with cells. The highest cellular uptake and retention under a magnetic field was observed using small magnetic cationic liposomes. However, magnetic cationic liposomes exhibited strong cytotoxicity. Based on these results, we constructed complexes of less toxic magnetic anionic liposomes (Mag-AL) and atelocollagen (ATCOL), a biocompatible cationic biomaterial. The cellular associated amount of Mag-AL under a magnetic field was significantly increased when Mag-AL was complexed with ATCOL, and it was comparable to that of magnetic cationic liposomes. Additionally, Mag-AL/ATCOL complexes produced no cytotoxic effect. Moreover, liver accumulation of Mag-AL/ATCOL complexes was significantly increased at a magnetic field-exposed region after intravenous injection in rats. These results indicate that Mag-AL/ATCOL complexes may be a safe and efficient magnetic responsive drug carrier. Next, we applied Mag-AL/ATCOL complexes to prepare magnetized cells for effective cell therapy. Mesenchymal stem cells (MSCs), which have the capacity to suppress tissue inflammation, were efficiently magnetized by incubation with Mag-AL/ATCOL complexes under a magnetic field. Intramuscularly injected magnetized MSCs were significantly retained in mouse skeletal muscle in the presence of a magnetic field and modulated tissue inflammatory responses. These results suggest that magnetized MSCs are useful for muscle regeneration.

Indocyanine Green-Containing Magnetic Liposomes for Constant Magnetic Field-Guided Targeted Delivery and Theranostics

The aim of the present study was to develop magnetic liposomes (MLPSs) incorporating an agent with the ability to act both as a photosensitizer and as a fluorophore for optical imaging. We therefore aimed to develop a preparation method for indocyanine green (ICG)-containing MLPS, followed by a detailed characterization of their physicochemical and magnetic properties. The ability of intravenously administered ICG-containing MLPSs to accumulate in tissue exposed to a constant magnetic field was tested in vivo. Using the thin film hydration method, 170-nm aqueous liposomes containing magnetic nanoparticles and indocyanine green were synthesized, followed by a detailed characterization of their physicochemical properties. It was shown that ICG-containing MLPSs possess the properties of T2 contrast for MRI. Apart from this, ICG-containing MLPSs were clearly visualized using near infrared fluorescent imaging, which was demonstrated in in vivo experiments showing an accumulation of ICG-containing MLPSs in the zone of magnetic field distribution produced by a previously implanted constant magnet in the tissue. Although not directly tested in the present study, therapeutic applications of ICG-containing MLPSs include magnetic hyperthermia, as well as the photodynamic, photothermal, and photoacoustic effects of ICG. Taking into account the fact that liposomes, iron oxide nanoparticles, and ICG are all FDA-approved agents, it is highly likely that ICG-containing MLPSs could be successfully translated to clinical practice.

Research on the Construction of Bispecific-Targeted Sustained-Release Drug-Delivery Microspheres and Their Function in Treatment of Hepatocellular Carcinoma.

Lenvatinib (LEN) is approved as one of the commonly used drugs in the treatment of hepatocellular carcinoma (HCC). It is recognized to be a novel therapeutic choice for the direct and targeted delivery of effective drugs to HCC tumor sites. The key to the proposed method lies in the requirement for efficient targeted drug delivery carriers with targeting performance to deliver effective drugs directly and safely to tumor lesions. Methods: Here, magnetic liposomes (MLs) were modified by phosphatidylinositol proteoglycan 3 (GPC3) and epithelial cell adhesion molecules (EpCAMs). Subsequently, bispecific-targeted sustained-release drug-loaded microspheres containing LEN (GPC3/EpCAM-LEN-MLs) were constructed. In addition, both cytotoxicity and magnetic resonance imaging (MRI) analyses were performed to establish a mouse model and further perform corresponding performance assessments. Results: The corresponding results showed that GPC3/EpCAM-LEN-MLs were spherical-shaped and evenly dispersed. The encapsulation and drug-loading efficiencies were 91.08% ± 1.83% and 8.22% ± 1.24%, respectively. Meanwhile, GPC3/EpCAM-LEN-MLs showed a high inhibition rate on the proliferation of HCC cells and significantly increased their apoptosis. Furthermore, MRI revealed that the system possessed the function of tracking and localizing tumor cells, and animal experiments verified that it could exert the function of disease diagnosis. Conclusions: Our experiments successfully constructed a safe and efficient bispecific-targeted sustained-release drug delivery system for HCC tumor cells. It provides a useful diagnostic and therapeutic scheme for the clinical diagnosis and targeted therapy of HCC. Moreover, it can be used as a potential tumor-specific MRI contrast agent for the localization and diagnosis of malignant tumors.

Targeting Peptide, Fluorescent Reagent Modified Magnetic Liposomes Coated with Rapamycin Target Early Atherosclerotic Plaque and Therapy.

Atherosclerosis is the leading cause of global morbidity and mortality. Its therapy requires research in several areas, such as diagnosis of early arteriosclerosis, improvement of the pharmacokinetics and bioavailability of rapamycin as its therapeutic agents. Here, we used the targeting peptide VHPKQHR (VHP) (or fluorescent reagent) to modify the phospholipid molecules to target vascular cell adhesion molecule-1 (VCAM-1) and loaded ultrasmall paramagnetic iron oxide (USPIO/Fe3O4) plus rapamycin (Rap) to Rap/Fe3O4@VHP-Lipo (VHPKQHR-modified magnetic liposomes coated with Rap). This nanoparticle can be used for both the diagnosis and therapy of early atherosclerosis. We designed both an ex vivo system with mouse aortic endothelial cells (MAECs) and an in vivo system with ApoE knockout mice to test the labeling and delivering potential of Rap/Fe3O4@VHP-Lipo with fluorescent microscopy, flow cytometry and MRI. Our results of MRI imaging and fluorescence imaging showed that the T2 relaxation time of the Rap/Fe3O4@VHP-Lipo group was reduced by 2.7 times and 1.5 times, and the fluorescence intensity increased by 3.4 times and 2.5 times, respectively, compared with the normal saline group and the control liposome treatment group. It showed that Rap/Fe3O4@VHP-Lipo realized the diagnosis of early AS. Additionally, our results showed that, compared with the normal saline and control liposomes treatment group, the aortic fluorescence intensity of the Rap/Fe3O4@VHP-Lipo treatment group was significantly weaker, and the T2 relaxation time was prolonged by 8.9 times and 2.0 times, indicating that the targeted diagnostic agent detected the least plaques in the Rap/Fe3O4@VHP-Lipo treatment group. Based on our results, the synthesized theragnostic Rap/Fe3O4@VHP-Lipo serves as a great label for both MRI and fluorescence bimodal imaging of atherosclerosis. It also has therapeutic effects for the early treatment of atherosclerosis, and it has great potential for early diagnosis and can achieve the same level of therapy with a lower dose of Rap.