Liposomes-enabled cancer chemoimmunotherapy.

Chemoimmunotherapy is an emerging paradigm in the clinic for treating several malignant diseases, such as non-small cell lung cancer, breast cancer, and large B-cell lymphoma. However, the efficacy of this strategy is still restricted by serious adverse events and a high therapeutic termination rate, presumably due to the lack of tumor-targeted distribution of both chemotherapeutic and immunotherapeutic agents. Targeted drug delivery has the potential to address this issue. Among the most promising nanocarriers in clinical translation, liposomes have drawn great attention in cancer chemoimmunotherapy in recent years. Liposomes-enabled cancer chemoimmunotherapy has made significant progress in clinics, with impressive therapeutic outcomes. This review summarizes the latest preclinical and clinical progress in liposome-enabled cancer chemoimmunotherapy and discusses the challenges and future directions of this field.

Preparation and characterization of astaxanthin-loaded liposomes by phytosterol oleate instead of cholesterol.

Hydrophobic bioactive compounds like astaxanthin (AST) exhibit poor water solubility and low bioavailability. Liposomes, which serve as nanocarriers, are known for their excellent biocompatibility and minimal immunogenicity. Traditionally, liposomes have been primarily constructed using phospholipids and cholesterol. However, the intake of cholesterol may pose a risk to human health. Phytosterol ester was reported to reduce level of cholesterol and improve properties of liposomes. In this study, phytosterol oleate was used to prepare liposomes instead of cholesterol to deliver AST (AST-P-Lip). The size range of AST-P-Lip was 100-220 nm, and the morphology was complete and uniform. In vitro studies showed that AST-P-Lip significantly enhanced the antioxidant activity and oral bioavailability of AST. During simulated digestion, AST-P-Lip protected AST from damage by gastric and intestinal digestive fluid. Additionally, AST-P-Lip had a good storage stability and safety. These results provide references for the preparation of novel liposomes and the delivery of bioactive compounds.

Thermosensitive multivesicular liposomal hydrogel: a potential platform for loco-regional drug delivery in the treatment of osteomyelitis caused by antibiotic-resistant biofilm-forming bacteria.

Biofilm-mediated osteomyelitis presents significant therapeutic challenges. Given the limitations of existing osteomyelitis treatment approaches, there is a distinct need to develop a localized drug delivery system that is biocompatible, biodegradable, and capable of controlled antibiotic release. Multivesicular liposomes (MVLs), characterized by their non-concentric vesicular structure, distinct composition, and enhanced stability, serve as the system for a robust sustained-release drug delivery platform. In this study, various hydrogel formulations composed of poloxamer 407 and other hydrogels, incorporating vancomycin hydrochloride (VAN HL) -loaded MVLs (VAN HL-MVL), were prepared and evaluated. The optimized VAN HL-MVL sol-gel system, consisting of poloxamer 407 and hyaluronic acid, successfully maintained drug release for up to three weeks and exhibited shear-thinning behavior at 37°C. While complete drug release from MVLs alone took place in 312 hours, the hydrogel formulation extended this release to 504 hours. The released drug effectively inhibited the Staphylococcus aureus biofilms growth within 24 hours and methicillin-resistant Staphylococcus aureus biofilms within 72 hours. It also eradicated pre-formed biofilms of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus in 96 and 120 hours, respectively. This injectable in situ gel system incorporating VAN HL-MVLs holds potential as an alternative to undergoing multiple surgeries for osteomyelitis treatment and warrants further studies.

Optimizing Transfection Efficiency of Spermine Polar Head Cholesterol-based Cationic Lipids with Amino Acid Linker.

In this work, a series of spermine polar head cholesterol-based cationic lipids with various amino acid spacers were synthesized and evaluated as non-viral gene delivery systems. The physicochemical properties of the resulting lipoplexes, formed from these lipids and DOPE, were assessed, including zeta-potential, DNA binding and DNA protection from serum. Transfection efficiency and cytotoxicity were examined under serum-free and 10-40% serum-containing conditions. The results showed that the physicochemical properties of cationic lipids, both with and without amino acid spacers, were not significantly different. Cationic liposomes composed of lipid Sper-Ahx-Chol, which has a 6-aminohexanoic acid spacer, and DOPE exhibited greater transfection efficiency in HeLa cells compared to Lipofectamine3000, both in the absence and presence of 10-40% serum. Additionally, lipid Sper-His-Chol with a histidine spacer and Sper-Ahx-Chol showed higher efficiency than Lipofectamine3000 against HEK293T under 40% serum conditions. These results suggest that the incorporation of amino acids into the cationic lipids can significantly enhance their DNA delivery efficiency. Specifically, certain amino acid modifications improved transfection efficiency while maintaining low cytotoxicity. Our findings highlight the potential of amino acid-tailored cationic lipids as promising vectors for enhanced DNA delivery.

Two hearts beat as one: the debate over RAS dimers continues.

A recent report by Yun et al. describes the detection of RAS dimers using intact mass spectrometry and investigates the role that membrane lipids, nucleotide state, and binding partners have in their formation.

MPS blockade with liposomes controls pharmacokinetics of nanoparticles in a size-dependent manner.

Pharmacokinetics of nanomedicines can be improved by a temporal blockade of mononuclear phagocyte system (MPS) through the interaction with other biocompatible nanoparticles. Liposomes are excellent candidates as blocking agents, but the efficiency of the MPS blockade can greatly depend on the liposome properties. Here, we investigated the dependence of the efficiency of the induced MPS blockade in vitro and in vivo on the size of blocking liposomes in the 100-500 nm range. Saturation of RAW 264.7 macrophage uptake was observed for phosphatidylcholine/cholesterol liposomes larger than 200 nm in vitro. In mice, liposomes of all sizes exhibited a blocking effect on liver macrophages, prolonging the circulation of subsequently administrated magnetic nanoparticles in the bloodstream, reducing their liver uptake, and increasing accumulation in the spleen and lungs. Importantly, these effects became more pronounced with the increase of liposome size. Optimization of the size of the blocking liposomes holds the potential to enhance drug delivery and improve cancer therapy.

In Situ Bioorthogonal Repair of the Vascular Endothelium Glycocalyx to Treat Acute Lung Injury.

In acute lung injury, destruction of the lung endothelial glycocalyx leads to vessel permeabilization and contributes to pulmonary edema and inflammation. Heparan sulfate, which accounts for >70% of glycosaminoglycans in the endothelial glycocalyx, plays a crucial physiological anti-inflammatory role. To treat acute lung injury, it is explored whether a two-step in vivo bioorthogonal chemistry strategy can covalently link intravenously administered heparan sulfate to the lung vascular endothelium and the damaged glycocalyx. First, fusogenic liposomes (EBP-Tz-FLs) carrying the reactive group tetrazine (Tz), and an E-selectin-binding peptide (EBP) to target the lung inflammatory endothelium are administered intravenously. This step aimed to anchor the tetrazine group to the membrane of inflammatory endothelial cells. Second, heparan sulfate (HS-TCO) conjugated to the trans-cyclooctene (TCO) group, which spontaneously reacts with Tz, is injected intravenously, leading to covalent heparan sulfate addition to the vascular endothelium. In a mouse model of acute lung injury, this approach substantially reduced vascular permeability and attenuated lung tissue infiltration. The EBP-Tz-FLs and HS-TCO showed favorable biocompatibility and safety both in vitro and in vivo. The proposed strategy shows good promise in acute lung injury therapy and covalently anchoring functional molecules onto the membrane of target cells.

A Novel Acoustic Modulation of Oscillating Thin Elastic Membrane for Enhanced Streaming in Microfluidics and Nanoscale Liposome Production.

Liposomes are widely utilized in therapeutic nanosystems as promising drug carriers for cancer treatment, which requires a meticulous synthesis approach to control the nanoprecipitation process. Acoustofluidic platforms offer a favorable synthesis environment by providing robust agitation and rapid mixing. Here, a novel high-throughput acoustofluidic micromixer is presented for a solvent and solvent-free synthesis of ultra-small and size-tunable liposomes. The size-tunability is achieved by incorporating glycerol as a new technique into the synthesis reagents, serving as a size regulator. The proposed device utilizes the synergistic effects of vibrating trapped microbubbles and an oscillating thin elastic membrane to generate vigorous acoustic microstreaming. The working principle and mixing mechanism of the device are explored numerically and experimentally. The platform exhibits remarkable mixing efficacy for aqueous and viscous solutions at flow rates up to 8000 µL/h, which makes it unique for high-throughput liposome formation and preventing aggregation. As a proof of concept, this study investigates the impact of phospholipid type and concentration, flow rate, and glycerol on the size and size distribution of liposomes. The results reveal a significant size reduction, from ≈900 nm to 40 nm, achieved by merely introducing 75% glycerol into the synthesis reagents, highlighting an innovative approach toward size-tunable liposomes.

Truncated mini LRP1 transports cargo from luminal to basolateral side across the blood brain barrier.

BACKGROUND: The most crucial area to focus on when thinking of novel pathways for drug delivery into the CNS is the blood brain barrier (BBB). A number of nanoparticulate formulations have been shown in earlier research to target receptors at the BBB and transport therapeutics into the CNS. However, no mechanism for CNS entrance and movement throughout the CNS parenchyma has been proposed yet. Here, the truncated mini low-density lipoprotein receptor-related protein 1 mLRP1_DIV* was presented as blood to brain transport carrier, exemplified by antibodies and immunoliposomes using a systematic approach to screen the receptor and its ligands' route across endothelial cells in vitro. METHODS: The use of mLRP1_DIV* as liposomal carrier into the CNS was validated based on internalization and transport assays across an in vitro model of the BBB using hcMEC/D3 and bEnd.3 cells. Trafficking routes of mLRP1_DIV* and corresponding cargo across endothelial cells were analyzed using immunofluorescence. Modulation of γ-secretase activity by immunoliposomes loaded with the γ-secretase modulator BB25 was investigated in co-cultures of bEnd.3 mLRP1_DIV* cells and CHO cells overexpressing human amyloid precursor protein (APP) and presenilin 1 (PSEN1). RESULTS: We showed that while expressed in vitro, mLRP1_DIV* transports both, antibodies and functionalized immunoliposomes from luminal to basolateral side across an in vitro model of the BBB, followed by their mLRP1_DIV* dependent release of the cargo. Importantly, functionalized liposomes loaded with the γ-secretase modulator BB25 were demonstrated to effectively reduce toxic Aß42 peptide levels after mLRP1_DIV* mediated transport across a co-cultured endothelial monolayer. CONCLUSION: Together, the data strongly suggest mLRP1_DIV* as a promising tool for drug delivery into the CNS, as it allows a straight transport of cargo from luminal to abluminal side across an endothelial monolayer and it's release into brain parenchyma in vitro, where it exhibits its intended therapeutic effect.

Development of a novel intramuscular liposomal injection for advanced meloxicam delivery: Preparation, characterization, in vivo pharmacokinetics, pharmacodynamics, and pain assessment in an orthopedic pain model.

Pain produces several physiological, and degenerative complications. This study aimed to formulate meloxicam (MLX) in liposomes to increase solubility and deliver MLX in a controlled manner to overcome its poor aqueous solubility and relatively short t1/2 problems. Liposomes were prepared by thin film hydration followed by ultrasonication. Tests for characterizing formulations included particle size, span, entrapment efficiency, drug loading, stability, differential scanning calorimetry (DSC), Fourier transformation infrared (FT-IR) spectroscopy, morphology, in vitro release, release kinetics mathematical modeling, and an in vivo pain model in dogs undergoing orthopedic surgeries, followed by in vivo pharmacokinetics, pharmacodynamics, and pain assessment studies in comparison to the reference standard, Mobitil®. Liposomal MLX had a particle size of around 100 nm, 82 % entrapment efficiency, and 4.62 % drug loading. Stability studies, DSC, and FT-IR spectroscopy indicated that liposomes were highly stable. The formulation showed an improved in vitro controlled release pattern and an enhanced in vivo pharmacokinetic behavior as manifested by higher t1/2 and AUC0 - 24 and lower Cl/F in comparison to Mobitil®. The pharmacodynamics study and pain scales demonstrated liposomal MLX managed postoperative pain better than Mobitil®. In conclusion, the incorporation of MLX in liposomes increased its solubility and stability, as well as its pain management properties.

Novel targeting liposomes with enhanced endosomal escape for co-delivery of doxorubicin and curcumin.

Effective endosomal escape is crucial for enhancing the efficiency of nanodrug delivery systems. In this study, we developed a novel liposomal system utilizing acid-sensitive N-(3-amino-propyl) imidazole cholesterol (IM-Chol), specifically designed for the targeted co-delivery of doxorubicin (DOX) and curcumin (CUR) to hepatocellular carcinoma (HCC). Designated as GA-IM-LIP@DOX/CUR, this liposomal system incorporates glycyrrhetinic acid (GA) to improve target specificity toward HCC cells. Notably, both drugs exhibited pH-sensitive release profiles, facilitating precise drug release within acidic environments. Our investigation into cellular uptake demonstrated that modified liposomes, GA-IM-LIP@FITC and IM-LIP@FITC, achieved progressively enhanced intracellular accumulation of FITC compared to unmodified liposomes. Competitive inhibition assays utilizing free GA further validated the targeting efficacy of GA. Moreover, the GA-IM-LIP@FITC and IM-LIP@FITC groups exhibited rapid endosomal escape of FITC within the first two hours, in contrast to delayed escape observed in the LIP@FITC group, confirming that the protonation of IM-Chol promotes drug release into the cytosol. In vivo studies substantiated that GA-IM-LIP@DOX/CUR effectively inhibited tumor growth. This research provides significant insights into the design and functionality of the GA-IM-LIP@DOX/CUR liposomal system, underscoring its potential to enhance drug delivery strategies in the treatment of HCC.

Dual Centrifugation-based Screening for pH-responsive Liposomes.

In liposomal drug delivery development, the delicate balance of membrane stability is a major challenge to prevent leakage (during shelf-life and blood circulation), and to ensure efficient payload release at the therapeutic destination. Our composite screening approach uses the processing by dual centrifugation technique to speed up the identification of de novo formulations of intermediate membrane stability. By screening binary lipid combinations at systemically varied ratios we highlight liposomal formulations of intermediate stability, what we termed "the edge of stability", requiring moderate stimuli for destabilization. Supplementation with a pH-sensitive cholesterol derivative (to obtain acid labile liposomes) and renewed assessment with cargo load led to the discovery of three formulations with sufficient shelf-life stability, acceptable cargo retention and efficient pH-responsive cargo release in vitro. The "lead candidates" exhibited promising in cellulo uptake with increased intracellular cargo release and revealed in vivo performance advantages compared to a control liposome. Our approach filters lipid compositions on "the edge of stability" that were introduced with a pH-sensitive cholesterol derivate leading pH-responsive liposomes, out of a multidimensional parameter space. Their discovery by rational approaches would have been highly unlikely, thus highlighting the potential of our screening approach.

Curcumin-Loaded Liposomes in Gel Protect the Skin of Mice against Oxidative Stress from Photodamage Induced by UV Irradiation.

Prolonged exposure to ultraviolet (UV) irradiation can cause oxidative stress in the skin, accompanied by rapid immunosuppressive effects, resulting in a peroxidation reaction throughout the body. Curcumin (Cur), as the bioactive compound of turmeric, is a natural polyphenol with potent antioxidant properties but is often overlooked due to its poor solubility and low bioavailability. In this study, curcumin-loaded liposomes in a sodium alginate gel complex preparation were designed to improve the bioavailability of curcumin and to study its preventive effect on photodamage. Cur-loaded liposomes (Cur-L), Cur-loaded gel (Cur-G) based on an alginate matrix, and curcumin-loaded liposomes in gel (Cur-LG) were prepared, and their antioxidant effects and drug diffusion abilities were evaluated. The antioxidant capacity of Cur, Cur-L, Cur-G, and Cur-LG was also studied in a mouse model of photodamage. Cur had the highest antioxidant activity at about 4 mg/mL. Cur-LG at this concentration showed antioxidant effects during 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH) and H2O2 experiments. During the UV light damage test, Cur-LG demonstrated the ability to effectively neutralize free radicals generated as a result of lipid peroxidation in the skin, serum, and liver, thereby enhancing the overall activity of superoxide dismutase (SOD). In conclusion, using Cur-LG may protect against epidermal and cellular abnormalities induced by UV irradiation.

Computational Designed and Optimized Liposomal Curcumin-Embedded Bifunctional Cross-Linked Hydrogels for Wound Healing.

Curcumin (CUR) bifunctional cross-linked nanocomposite hydrogels are presented as an efficient method for CUR delivery in wound healing. CUR-loaded liposomes (CUR-Ls) were optimized using the Box-Behnken design to augment particle size, size distribution, zeta potential, and CUR concentration. The antioxidant activity and cytotoxicity of CUR-Ls were assessed. Hyaluronic acid (HA)/poly(vinyl alcohol) (PVA) hydrogels were optimized with a central composite design; then, poly(N-vinylpyrrolidone-co-itaconic acid) (PNVP-ITA) was synthesized to enrich the properties of the hydrogels. The drug release kinetics of the CUR-L@HA/PVA/PNVP-ITA hydrogels were studied. Skin recovery was investigated in vivo on rat dorsal skin. The optimized CUR-Ls were constructed from 2.7% Tween® 20, 0.04% oleic acid, and 8.1% CUR, yielding nano-CUR-L with a narrow size distribution, negative surface charge, and CUR content of 19.92 ± 0.54 µg/mg. CUR-Ls improved the antioxidant effects of CUR. The optimized hydrogel contained 5% HA and 10% PVA. PNVP-ITA improved the properties of the hydrogels via enhanced cross-linking. CUR-Ls exhibited a more rapid release than CUR, whereas the hydrogels enhanced CUR release via a diffusion-controlled mechanism. CUR-L@HA/PVA/PNVP-ITA hydrogels improved the skin recovery rate compared to the commercial patch after 5 days. Therefore, the optimized CUR-L@HA/PVA/PNVP-ITA hydrogels facilitated skin recovery and could be a promising nanocomposite for wound dressings.

Anti-Coronavirus Activity of Chitosan-Stabilized Liposomal Nanocarriers Loaded with Natural Extracts from Bulgarian Flora.

Disease's severity, mortality rates, and common failures to achieve clinical improvement during the unprecedented COVID-19 pandemic exposed the emergency need for new antiviral therapeutics with higher efficacy and fewer adverse effects. This study explores the potential to encapsulate multi-component plant extracts in liposomes as optimized delivery systems and to verify if they exert inhibitory effects against human seasonal betacoronavirus OC43 (HCoV-OC43) in vitro. The selection of Sambucus nigra, Potentilla reptans, Allium sativum, Aesculus hippocastanum, and Glycyrrhiza glabra L. plant extracts was based on their established pharmacological and antiviral properties. The physicochemical characterization of extract-loaded liposomes was conducted by DLS and electrokinetics. Encapsulated amounts of the extract were evaluated based on the total flavonoid content (TFC) and total polyphenol content (TPC) by colorimetric methods. The BALB 3T3 neutral red uptake (NRU) phototoxicity/cytotoxicity assay was used to estimate compounds' safety. Photo irritation factors (PIFs) of the liposomes containing extracts were <2 which assigned them as non-phototoxic substances. The antiviral capacities of liposomes containing medicinal plant extracts against HCoV-OC43 were measured by the cytopathic effect inhibition test in susceptible HCT-8 cells. The antiviral activity increased by several times compared to "naked" extracts' activity reported previously. A. hippocastanum extract showed 16 times higher inhibitory properties reaching a selectivity index (SI) of 58.96. Virucidal and virus-adsorption effects were investigated using the endpoint dilution method and ∆lgs comparison with infected and untreated controls. The results confirmed that nanoparticles do not directly affect the viral surface or cell membrane, but only serve as carriers of the active substances and the observed protection is due solely to the intracellular action of the extracts.

In vivo reduction of skin inflammation using ferulic acid-loaded lipid vesicles derived from Brewer's spent grain.

Brewers spent grain (BSG) is the main by-product of the brewing industry, and due to its rapid decomposition, it generates serious environmental problems such as malodors and greenhouse gases emissions. On the other hand, this lignocellulosic compound contains a large number of antioxidants, being ferulic acid (FA) the most abundant. FA is a powerful antioxidant molecule that has demonstrated significant protective effects on key components of the skin, including keratinocytes, fibroblasts, collagen, and elastin. FA inhibits melanogenesis, promotes angiogenesis and accelerates the wound healing although its use is limited by its rapid oxidation. In this study, different hydrolysis treatments (chemical, enzymatic and hydrothermal) were performed on BSG to obtain FA. Herein FA-loaded ultradeformable liposomes (ULs) were designed to improve their stability and in vivo performance. These nanosystems allow FA permeability through human skin, as proven by an ex vivo skin permeability assay using Franz diffusion cells. The toxicity and anti-inflammatory activity of the formulation has been investigated. The free form and 100 nm FA_ULs were evaluated. Cell viability was dose-dependent and provided optimal results for the treatment of inflammatory skin conditions in an in vivo Oxazolone-induced Delayed Type Hypersensitivity model using Swiss CD1 mice, demonstrated by the reduction of the inflammatory cytokines expression, ear thickness, bioluminescence and histological evaluation. These results pave the way for FA-based treatments of skin and inflammatory conditions.

Nano-vesicular systems for melanocytes targeting and melasma treatment: In-vitro characterization, ex-vivo skin retention, and preliminary clinical appraisal.

Melasma represents an acquired melanogenesis disorder resulting in skin's hyperpigmentation effect. Although several approaches are adopted for melasma treatment, nanotechnology presents the most convenient one. Therefore, the present work aimed to formulate and characterize three nano-vesicular systems namely, liposomes, penetration enhancer containing vesicles (PEVs) and invasomes to enhance the topical delivery of the skin whitening agent; alpha arbutin (α-arbutin) for the treatment of melasma. Liposomes were prepared according to a 23 full factorial design and the selected formula was further employed for the preparation of PEVs and invasomes. Results showed that the three vesicular systems exhibited nano-sizes ranging from 151.95 to 672.5 nm, negative charges ranging from -12.50 to -28.20 mV, high entrapment efficiencies ranging from 80.59 to 99.53 %, good stability and prolonged-release of α-arbutin for 24 h after dispersion in hydrogel form. The deposition study from the vesicular hydrogel confirmed their effectiveness for the drug's accumulation in the skin reaching an average of 1.6-fold higher in the stratum corneum, 1.6-1.8-fold higher in the epidermis, and 1.6-1.8-fold higher in the dermis compared to the free drug dispersion in hydrogel. A preliminary clinical split-face study on patients suffering from melasma revealed that α-arbutin-loaded liposomes and PEVs in hydrogel forms showed better clinical outcomes compared to the free α-arbutin hydrogel as well as to the previously published α-arbutin encapsulated in chitosan nanoparticles and dispersed in hydrogel form. This delineates the aforementioned nano-vesicular systems as effective and clinically superior delivery means for melasma management.

Scanning Electron Microscopy (SEM) Evaluation of the Ultrastructural Effects on Conjunctival Epithelial Cells of a New Multiple-Action Artificial Tear Containing Cross-Linked Hyaluronic Acid, Cationic Liposomes and Trehalose.

The authors performed an ex vivo and in vivo evaluation of the ultrastructural effects on the conjunctival epithelial cells of a new multiple-action tear substitute containing cross-linked hyaluronic acid, lipids and trehalose (Trimix®), using scanning electron microscopy (SEM) with conjunctival impression cytology. The ex vivo study highlights the persistence and distribution of the product at 5 and 60 min on a monolayer of conjunctival epithelial cells and an increase in microvilli density at the 60 min evaluation. In vivo examination was conducted on three subjects with different grades of ocular surface inflammation, treated with one drop of the product twice daily for thirty days. At the baseline (T0) and twelve hours after the last administration of the tear drop (T30), impression cytology of the upper bulbar conjunctiva for SEM evaluation of conjunctival epithelial cells was carried out. Slit lamp examination (SLE), corneal and conjunctival Fluotest, tear film break-up time (TBUT), and ocular surface disease index (OSDI) questionnaires were also performed to correlate the ultrastructural results with the clinical findings. After 30 days of treatment, a significant improvement in all clinical and symptomatic parameters and in the condition of the ocular surface was detected, with microvillar regeneration and strengthening in all the patients, and a complete restoration in 2/3 of them. The persistence and distribution of the product on the epithelial cells was also noted 12 h after the last administration. The results, therefore, suggest a marked epitheliotropic effect along with a high residence time of the tear substitute.

Elevated Cellular Uptake of Succinimide- and Glucose-Modified Liposomes for Blood-Brain Barrier Transfer and Glioblastoma Therapy.

The uptake of four liposomal formulations was tested with the murine endothelial cell line bEnd.3 and the human glioblastoma cell line U-87 MG. All formulations were composed of DPPC, cholesterol, 5 mol% of mPEG (2000 Da, conjugated to DSPE), and the dye DiD. Three of the formulations had an additional PEG chain (nominally 5000 Da, conjugated to DSPE) with either succinimide (NHS), glucose (PEG-bound at C-6), or 4-aminophenyl ß-D-glucopyranoside (bound at C-1) as ligands at the distal end. Measuring the uptake kinetics at 1 h and 3 h for liposomal incubation concentrations of 100 µM, 500 µM, and 1000 µM, we calculated the liposomal uptake saturation S and the saturation half-time t1/2. We show that only succinimide has an elevated uptake in bEnd.3 cells, which makes it a very promising and so far largely unexplored candidate for BBB transfer and brain cancer therapies. Half-times are uniform at low concentrations but diversify for high concentrations for bEnd.3 cells. Contrary, U-87 MG cells show almost identical saturations for all three ligands, making a uniform uptake mechanism likely. Only mPEG liposomes stay at 60% of the saturation for ligand-coated liposomes. Half-times are diverse at low concentrations but unify at high concentrations for U-87 MG cells.

Exploring the functionality of fluorescent liposomes in cancer: diagnosis and therapy.

Fluorescent liposomes are pivotal in cancer research, serving as adaptable vehicles for imaging and therapeutics. These small lipid vesicles, capable of encapsulating fluorescent dyes, offer precise visualization and monitoring of their targeted delivery to cancer cells. This review delves into the critical role fluorescent liposomes play in enhancing both cancer diagnosis and treatment. It provides an in-depth analysis of their structural features, fluorescent labeling techniques, targeting strategies, and the challenges and opportunities they present. In the domain of cancer diagnosis, the article sheds light on various imaging modalities enabled by fluorescent liposomes, including fluorescence imaging and multimodal techniques. Emphasis is placed on early detection strategies, exhibiting the utility of targeted contrast agents and biomarker recognition for enhanced diagnostic precision. Moving on to cancer treatment, the review discusses the sophisticated drug delivery mechanisms facilitated by fluorescent liposomes, focusing on chemotherapy and photodynamic therapy. Moreover, the exploration extends to targeted therapy, explaining the applications of fluorescent liposomes in gene delivery and RNA interference. In a nutshell, his article comprehensively explores the multifaceted impact of fluorescent liposomes on advancing cancer diagnosis and treatment, combining existing knowledge with emerging trends.