ABSTRACT
Lipid-porphyrin conjugates are considered nowadays as promising building blocks for the conception of drug delivery systems with multifunctional properties such as photothermal therapy (PTT), photodynamic therapy (PDT), phototriggerable release, photoacoustic and fluorescence imaging. For this aim, we have recently synthesized a new lipid-porphyrin conjugate named PhLSM. This was obtained by coupling pheophorbide-a (Pheo-a), a photosensitizer derived from chlorophyll-a, to egg lyso-sphingomyelin. The pure PhLSMs were able to self-assemble into vesicle-like structures that were however not stable and formed aggregates with undefined structures due to the mismatch between the length of the alkyl chain in sn-1 position and the adjacent porphyrin. Herein, stable PhLSMs lipid bilayers were achieved by mixing PhLSMs with cholesterol which exhibits a complementary packing parameter. The interfacial behavior as well as the fine structures of their equimolar mixture was studied at the air/buffer interface by the mean of Langmuir balance and x-ray reflectomerty (XRR) respectively. Our XRR analysis unraveled the monolayer thickening and the increase in the lateral ordering of PhLSM molecules. Interestingly, we could prepare stable vesicles with this mixture that encapsulate hydrophilic fluorescent probe. The light-triggered release kinetics and the photothermal conversion were studied. Moreover, the obtained vesicles were photo-triggerable and allowed the release of an encapsulated cargo in an ON-OFF fashion.
Subject(s)
Drug Delivery Systems , Lipids/chemistry , Phospholipids/chemistry , Porphyrins/chemistry , Chlorophyll/analogs & derivatives , Chlorophyll/chemical synthesis , Chlorophyll/chemistry , Cholesterol/chemistry , Humans , Hydrophobic and Hydrophilic Interactions/radiation effects , Kinetics , Light , Lipid Bilayers/chemistry , Lipid Bilayers/radiation effects , Lipids/chemical synthesis , Lipids/radiation effects , Lipids/therapeutic use , Liposomes/chemistry , Liposomes/radiation effects , Liposomes/therapeutic use , Phospholipids/chemical synthesis , Phospholipids/pharmacology , Phospholipids/radiation effects , Photochemotherapy/trends , Photosensitizing Agents/chemical synthesis , Photosensitizing Agents/chemistry , Photosensitizing Agents/radiation effects , Photothermal Therapy/trends , Porphyrins/chemical synthesis , Porphyrins/radiation effects , Porphyrins/therapeutic useABSTRACT
Background: Immunotherapy has profoundly changed the landscape of cancer management and represented the most significant breakthrough. Yet, it is a formidable challenge that the majority of cancers - the so-called "cold" tumors - poorly respond to immunotherapy. To find a general immunoregulatory modality that can be applied to a broad spectrum of cancers is an urgent need. Methods: Magnetic hyperthermia (MHT) possesses promise in cancer therapy. We develop a safe and effective therapeutic strategy by using magnetism-mediated targeting MHT-immunotherapy in "cold" colon cancer. A magnetic liposomal system modified with cell-penetrating TAT peptide was developed for targeted delivery of a CSF1R inhibitor (BLZ945), which can block the CSF1-CSF1R pathway and reduce M2 macrophages. The targeted delivery strategy is characterized by its magnetic navigation and TAT-promoting intratumoral penetration. Results: The liposomes (termed TAT-BLZmlips) can induce ICD and cause excessive CRT exposure on the cell surface, which transmits an "eat-me" signal to DCs to elicit immunity. The combination of MHT and BLZ945 can repolarize M2 macrophages in the tumor microenvironment to relieve immunosuppression, normalize the tumor blood vessels, and promote T-lymphocyte infiltration. The antitumor effector CD8+ T cells were increased after treatment. Conclusion: This work demonstrated that TAT-BLZmlips with magnetic navigation and MHT can remodel tumor microenvironment and activate immune responses and memory, thus inhibiting tumor growth and recurrence.
Subject(s)
Colonic Neoplasms/therapy , Combined Modality Therapy/methods , Hyperthermia , Immunotherapy/methods , Liposomes/chemistry , Magnetic Field Therapy/methods , Magnetite Nanoparticles/chemistry , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/antagonists & inhibitors , Animals , Apoptosis/drug effects , Apoptosis/radiation effects , Benzothiazoles/pharmacokinetics , Benzothiazoles/pharmacology , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/metabolism , Cell Line, Tumor , Colonic Neoplasms/diagnostic imaging , Colonic Neoplasms/immunology , Female , Humans , Liposomes/metabolism , Liposomes/radiation effects , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/therapy , Picolinic Acids/pharmacokinetics , Picolinic Acids/pharmacology , Rats , Tumor Microenvironment/drug effects , Tumor-Associated Macrophages/drug effects , Tumor-Associated Macrophages/metabolism , Xenograft Model Antitumor AssaysABSTRACT
We report a simple and direct fluorimetric vesicle-based method for measuring the transport rate of the light-driven ions pumps as specifically applied to the chloride pump, halorhodopsin, from Natronomonas pharaonis (pHR). Previous measurements were cell-based and methods to determine average single channel permeability challenging. We used a water-in-oil emulsion method for directional pHR reconstitution into two different types of vesicles: lipid vesicles and asymmetric lipid-block copolymer vesicles. We then used stopped-flow experiments combined with fluorescence correlation spectroscopy to determine per protein Cl- transport rates. We obtained a Cl- transport rate of 442 (±17.7) Cl-/protein/s in egg phosphatidyl choline (PC) lipid vesicles and 413 (±26) Cl-/protein/s in hybrid block copolymer/lipid (BCP/PC) vesicles with polybutadine-polyethylene oxide (PB12PEO8) on the outer leaflet and PC in the inner leaflet at a photon flux of 1450 photons/protein/s. Normalizing to a per photon basis, this corresponds to 0.30 (±0.07) Cl-/photon and 0.28 (±0.04) Cl-/photon for pure PC and BCP/PC hybrid vesicles respectively, both of which are in agreement with recently reported turnover of ~500 Cl-/protein/s from flash photolysis experiments and with voltage-clamp measurements of 0.35 (±0.16) Cl-/photon in pHR-expressing oocytes as well as with a pHR quantum efficiency of ~30%.
Subject(s)
Chlorides/metabolism , Halorhodopsins/chemistry , Ion Transport/genetics , Liposomes/chemistry , Chlorides/chemistry , Chlorides/radiation effects , Halobacteriaceae/chemistry , Halobacteriaceae/genetics , Halorhodopsins/genetics , Kinetics , Light , Liposomes/metabolism , Liposomes/radiation effectsABSTRACT
Artificial systems capable of self-sustained movement with self-sufficient energy are of high interest with respect to the development of many challenging applications, including medical treatments, but also technical applications. The bottom-up assembly of such systems in the context of synthetic biology is still a challenging task. In this work, we demonstrate the biocompatibility and efficiency of an artificial light-driven energy module and a motility functional unit by integrating light-switchable photosynthetic vesicles with demembranated flagella. The flagellar propulsion is coupled to the beating frequency, and dynamic ATP synthesis in response to illumination allows us to control beating frequency of flagella in a light-dependent manner. In addition, we verified the functionality of light-powered synthetic vesicles in in vitro motility assays by encapsulating microtubules assembled with force-generating kinesin-1 motors and the energy module to investigate the dynamics of a contractile filamentous network in cell-like compartments by optical stimulation. Integration of this photosynthetic system with various biological building blocks such as cytoskeletal filaments and molecular motors may contribute to the bottom-up synthesis of artificial cells that are able to undergo motor-driven morphological deformations and exhibit directional motion in a light-controllable fashion.
Subject(s)
Artificial Cells , Axoneme/radiation effects , Cell Engineering/methods , Chlamydomonas reinhardtii/cytology , Flagella/radiation effects , Light , Adenosine Triphosphate/metabolism , Axoneme/metabolism , Cell Movement/radiation effects , Cilia/radiation effects , Dyneins/metabolism , Energy Metabolism/radiation effects , Flagella/metabolism , Kinesins/metabolism , Liposomes/metabolism , Liposomes/radiation effects , Photosynthesis/radiation effects , Signal Transduction/radiation effectsABSTRACT
Light is a uniquely powerful tool for controlling molecular events in biology. No other external input (e.g., heat, ultrasound, magnetic field) can be so tightly focused or so highly regulated as a clinical laser. Drug delivery vehicles that can be photonically activated have been developed across many platforms, from the simplest "caging" of therapeutics in a prodrug form, to more complex micelles and circulating liposomes that improve drug uptake and efficacy, to large-scale hydrogel platforms that can be used to protect and deliver macromolecular agents including full-length proteins. In this Review, we discuss recent innovations in photosensitive drug delivery and highlight future opportunities to engineer and exploit such light-responsive technologies in the clinical setting.
Subject(s)
Drug Delivery Systems , Light , Animals , Biocompatible Materials/administration & dosage , Biocompatible Materials/radiation effects , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/radiation effects , Humans , Liposomes/administration & dosage , Liposomes/radiation effects , Micelles , Prodrugs/administration & dosage , Prodrugs/radiation effectsABSTRACT
Stroke is a lethal cerebral disease with severe sequelae and high mortality. Microglia, the main immune cell in the cerebrum, possess therapeutic potential for strokes as its specific anti-inflammatory phenotype can reduce inflammation and promote neuron regeneration. However, the on-demand anti-inflammatory polarization of microglia at the stroke site is uncontrollable for therapeutic application. Here, we develop a platelet hybrid microglia platform which can specifically polarize to the anti-inflammatory phenotype by ultrasound irradiation for targeted cerebrum repair after stroke. The engineered microglia have strong adherence to the injured cerebral vessels with platelet membrane fusion and realize on-demand anti-inflammatory polarization with ultrasound-responsive IL-4 liposome decoration. The intravenously injected microglia platform showed anti-inflammatory polarization at the stroke site with insonation, and accelerated the M2-type polarization of endogenous microglia for long-term stroke recovery. Satisfied prognoses were achieved with reduced apoptosis, promoted neurogenesis, and functional recovery, indicating the implications of the microglia platform for stroke therapy.
Subject(s)
Blood Platelets/metabolism , Inflammation/therapy , Ischemic Stroke/therapy , Microglia/metabolism , Animals , Apoptosis/physiology , Blood Platelets/chemistry , Cell Engineering , Infarction, Middle Cerebral Artery/complications , Infarction, Middle Cerebral Artery/metabolism , Infarction, Middle Cerebral Artery/therapy , Inflammation/etiology , Inflammation/metabolism , Interleukin-4/chemistry , Interleukin-4/metabolism , Ischemic Stroke/complications , Ischemic Stroke/metabolism , Liposomes/chemistry , Liposomes/radiation effects , Male , Mice, Inbred C57BL , Microglia/chemistry , Neurogenesis/physiology , Protoporphyrins/chemistry , Recovery of Function/physiology , Ultrasonic WavesABSTRACT
Recent developments in the field of polymer vesicles, i.e. polymersomes, have demonstrated that disrupting the equilibrium conditions of the milieu could lead to shape transformation into stable non-spherical morphologies, bringing on-demand shape control to reality and bearing great promise for cell mimicry and a variety of biomedical applications. Here, we studied the self-assembly behavior of glassy amphiphilic triblock copolymers, poly(ethylene glycol)-block-polystyrene-stat-poly(coumarin methacrylate)-block-poly(ethylene glycol) (PEG-b-P(S-stat-CMA)-b-PEG), and their response to various stimuli. By changing the respective molecular weights of both the hydrophobic P(S-stat-CMA) and the hydrophilic PEG blocks, we varied the hydrophobic volume fraction thereby accessing a range of morphologies from spherical and worm-like micelles, as well as polymersomes. For the latter, we observed that slow osmotic pressure changes induced by dialysis led to a decrease in size while rapid osmotic pressure changes by addition of a PEG fusogen led to morphological transformations into rod-like and tubular polymersomes. We also found out that chemically crosslinking the vesicles before inducing osmotic pressure changes led to the vesicles exhibiting hypotonic shock, atypical for glassy polymersomes. We believe that this approach combining the robustness of triblock copolymers and light-based transformations will help expand the toolbox to design ever more complex biomimetic constructs.
Subject(s)
Liposomes/chemistry , Polyethylene Glycols/chemistry , Polymethacrylic Acids/chemistry , Polystyrenes/chemistry , Dialysis , Liposomes/radiation effects , Osmotic Pressure , Polyethylene Glycols/chemical synthesis , Polyethylene Glycols/radiation effects , Polymethacrylic Acids/chemical synthesis , Polymethacrylic Acids/radiation effects , Polystyrenes/chemical synthesis , Polystyrenes/radiation effects , Ultraviolet RaysABSTRACT
OBJECTIVE: To determine the effect of extracorporeal shock wave (ESWT) on liposomal bupivacaine in a tibial-plateau-leveling osteotomy model. STUDY DESIGN: In vitro study. SAMPLE POPULATION: Ten samples per group. METHODS: In addition to a control group (sham treatment), five treatment groups were defined as A, energy (E) 3 (0.22 mJ/mm2 ), 360 pulses per minute (p/m); B, E6 (0.29 mJ/mm2 ), 360 p/m; C, E8 (0.39 mJ/mm2 ), 360 p/m; D, E6, 480 p/m; E, E8 480 p/m. Two-milliliter aliquots of liposomal bupivacaine were placed in a gelatin chamber and treated with 1000 pulses according to group. All samples remained in the chamber for 170 seconds to reflect the longest treatment group. Free bupivacaine concentrations were determined after treatment with high-performance liquid chromatography. RESULTS: The median free bupivacaine concentration was reported as control, 1.90 mg/mL; A, 2.10 mg/mL; B, 2.03 mg/mL; C, 2.94 mg/mL; D, 2.71 mg/mL; E, 4.35 mg/mL. Groups C (P = .027), D (P = .034), and E (P = .002) were different from the control group. Groups C (P = .0025) and D (P = .0025) were different from group E. Additional intertreatment group differences were found. CONCLUSION: Extracorporeal shock wave therapy caused a dose-dependent release of bupivacaine; however, there was no significant release of bupivacaine from liposomes when ESWT was applied at currently recommended therapeutic settings in this model. CLINICAL SIGNIFICANCE: This in vitro study provides evidence that concurrent electrohydraulic ESWT and liposomal bupivacaine is likely safe at currently recommended settings, however, higher energy and pulse frequency settings should be avoided.
Subject(s)
Anesthetics, Local/metabolism , Bupivacaine/metabolism , Extracorporeal Shockwave Therapy/veterinary , Liposomes/radiation effects , Osteotomy/veterinary , Tibia/surgery , Anesthetics, Local/administration & dosage , Animals , Bupivacaine/administration & dosage , Disease Models, Animal , Dogs , In Vitro TechniquesABSTRACT
The emerging nanomedicine therapeutics have incorporated photonics technologies to develop precise medical treatment. Among the light regulated approaches, light-induced liposome technology has been explored and developed as a novel tool for spatiotemporal control of cargo release. Compared with the traditional liposome formulation, this triggering feature largely enhanced the therapeutic efficacy and minimized the side effects of the therapeutic substance. In this review paper, we discussed the basics of the light-induced liposomes including the engineering methods and photoresponsiveness mechanisms. We also reviewed current biomedical studies relating to light-induced liposome delivery systems, with an emphasis in the field of cancer therapy.
Subject(s)
Antineoplastic Agents/therapeutic use , Light , Liposomes/radiation effects , Neoplasms/drug therapy , Antineoplastic Agents/chemistry , Drug Delivery Systems , Humans , Liposomes/chemistry , Nanomedicine , Precision MedicineABSTRACT
Archaeal lipids ensure unprecedented stability of archaea membranes in extreme environments. Here, we incorporate a characteristic structural feature of an archaeal lipid, the cyclopentane ring, into hydrocarbon chains of a short-chain (C12) phosphatidylcholine to explore whether the insertion would allow such a lipid (1,2-di-(3-(3-hexylcyclopentyl)-propanoate)-sn-glycero-3-phosphatidylcholine, diC12cp-PC) to form stable bilayers at room temperature. According to fluorescence-based assays, in water diC12cp-PC formed liquid-crystalline bilayers at room temperature. Liposomes produced from diC12cp-PC retained calcein for over a week when stored at +4 °C. diC12cp-PC could also form model bilayer lipid membranes that were by an order of magnitude more stable to electrical breakdown than egg PC membranes. Molecular dynamics simulation showed that the cyclopentane fragment fixes five carbon atoms (or four C-C bonds), which is compensated by the higher mobility of the rest of the chain. This was found to be the reason for the remarkable stability of the diC12cp-PC bilayer: restricted conformational mobility of a chain segment increases the membrane bending modulus (compared to a normal hydrocarbon chain of the same length). Here, higher stiffness practically does not affect the line tension of a membrane pore edge. Rather it makes it more difficult for diC12cp-PC to rearrange in order to line the edge of a hydrophilic pore; therefore, fewer pores are formed.
Subject(s)
Archaea/chemistry , Cyclopentanes/chemistry , Hydrophobic and Hydrophilic Interactions/drug effects , Phospholipids/chemistry , Electricity/adverse effects , Lipid Bilayers/radiation effects , Liposomes/chemistry , Liposomes/radiation effects , Molecular Conformation/radiation effects , Water/chemistryABSTRACT
A kind of light-responsive vesicle was prepared by aqueous self-assembly of α-CD and an azobenzene-containing M-helical foldamer, which displayed dynamic disassembly-reassembly structural transformation when alternately irradiated by UV and visible light. Distinctively, this vesicle also exhibited enantioselective release abilities toward racemic propranolol (a ß-blocker), owing to the M-helical building blocks.
Subject(s)
Drug Carriers/chemistry , Liposomes/chemistry , alpha-Cyclodextrins/chemistry , Azo Compounds/chemistry , Azo Compounds/radiation effects , Drug Carriers/radiation effects , Drug Liberation/radiation effects , Liposomes/radiation effects , Molecular Conformation , Propranolol/chemistry , Quinolines/chemistry , Quinolines/radiation effects , Stereoisomerism , Ultraviolet Rays , alpha-Cyclodextrins/radiation effectsABSTRACT
This paper researches a suitable mathematical model that can reliably predict the release of a model drug (namely calcein) from biologically targeted liposomal nanocarriers triggered by ultrasound. Using mathematical models, curve fitting is performed on a set of five experimental acoustic drug release runs from Albumin-, Estrone-, and RGD-based Drug Delivery Systems (DDS). The three moieties were chosen to target specific cancers using receptor-mediated endocytosis. The best-fitting mathematical model is then enhanced using a Kalman filtering (KF) algorithm to account for the statistics of the dynamic and measurements noise sequences in predicted drug release. Unbiased drug-release estimates are realized by implementing an online noise identification algorithm. The algorithm is first deployed in a simulated environment in which it was rigorously tested and compared with the correct solution. Then, the algorithm was used to process the five experimental datasets. The results suggest that the Adaptive Kalman Filter (AKF) is exceptionally good at handling drug release estimation problems with a priori unknown or with changing noise covariances. In comparison with the KF, the AKF approach exhibited as low as a 69% reduction in the level of error in estimating the drug release state. Finally, the proposed algorithm is not computationally demanding and is capable of online estimation tasks.
Subject(s)
Drug Delivery Systems/methods , Drug Liberation/radiation effects , Liposomes/chemistry , Ultrasonic Waves , Algorithms , Fluoresceins/pharmacokinetics , Fluorescent Dyes/pharmacokinetics , Liposomes/radiation effectsABSTRACT
The sun is the most abundant source of energy on earth. Phototrophs have discovered clever strategies to harvest this light energy and convert it to chemical energy for biomass production. This is achieved in light-harvesting complexes, or antennas, that funnel the exciton energy into the reaction centers. Antennas contain an array of chlorophylls, linear tetrapyrroles, and carotenoid pigments spatially controlled by neighboring proteins. This fine-tuned regulation of protein-pigment arrangements is crucial for survival in the conditions of both excess and extreme light deficit. Photomedicine and photodiagnosis have long been utilizing naturally derived and synthetic monomer dyes for imaging, photodynamic and photothermal therapy; however, the precise regulation of damage inflicted by these therapies requires more complex architectures. In this Account, we discuss how two mechanisms found in photosynthetic systems, photoprotection and light harvesting, have inspired scientists to create nanomedicines for more effective and precise phototherapies. Researchers have been recapitulating natural photoprotection mechanisms by utilizing carotenoids and other quencher molecules toward the design of photodynamic molecular beacons (PDT beacons) for disease-specific photoactivation. We highlight the seminal studies describing peptide-linked porphyrin-carotenoid PDT beacons, which are locally activated by a disease-specific enzyme. Examples of more advanced constructs include tumor-specific mRNA-activatable and polyionic cell-penetrating PDT beacons. An alternative approach toward harnessing photosynthetic processes for biomedical applications includes the design of various nanostructures. This Account will primarily focus on organic lipid-based micro- and nanoparticles. The phenomenon of nonphotochemical quenching, or excess energy release in the form of heat, has been widely explored in the context of porphyrin-containing nanomedicines. These quenched nanostructures can be implemented toward photoacoustic imaging and photothermal therapy. Upon nanostructure disruption, as a result of tissue accumulation and subsequent cell uptake, activatable fluorescence imaging and photodynamic therapy can be achieved. Alternatively, processes found in nature for light harvesting under dim conditions, such as in the deep sea, can be harnessed to maximize light absorption within the tissue. Specifically, high-ordered dye aggregation that results in a bathochromic shift and increased absorption has been exploited for the collection of more light with longer wavelengths, characterized by maximum tissue penetration. Overall, the profound understanding of photosynthetic systems combined with rapid development of nanotechnology has yielded a unique field of nature-inspired photomedicine, which holds promise toward more precise and effective phototherapies.
Subject(s)
Carotenoids/therapeutic use , Liposomes/chemistry , Nanomedicine/methods , Nanoparticles/chemistry , Neoplasms/drug therapy , Porphyrins/therapeutic use , Animals , Biomimetics/methods , Carotenoids/chemistry , Carotenoids/radiation effects , Chickens , Light , Lipoproteins, HDL/chemistry , Liposomes/radiation effects , Mice , Nanoparticles/radiation effects , Neoplasms/diagnostic imaging , Photosynthesis , Porphyrins/chemistry , Porphyrins/radiation effectsABSTRACT
Photodynamic therapy (PDT) as a promising noninvasive and effective treatment modality has been clinically approved for cancer therapy. However, the poor selectivity of tumor and hypoxia-induced resistance constrain PDT efficacy immensely. To further enhance PDT's potency, we developed a drug delivery system based on liposome combining PDT and chemotherapeutics. The lipophilic IR780 was loaded into the lipid bilayer while hydrophilic chemotherapeutic agent tirapazamine (TPZ) was encapsulated in the hydrophilic core. IR780 could generate reactive oxygen species and hypoxic microenvironment in local site because of the continuous consumption of oxygen, resulting in the TPZ encapsulated in the aqueous liposome chamber brings out TPZ radicals to cause DNA double-strand breaks and chromosome aberrations. In vivo studies demonstrated that the liposomes which encapsulate IR780 and TPZ showed great antitumor efficacy via combining photodynamic therapy with chemotherapy. Therefore, the investigation combines PDT and hypoxia-activated chemotherapy from the TPZ. It is a simple but effective liposome platform to achieve multiple synergistic antitumor efficacy and shows potential for clinical use.
Subject(s)
Antineoplastic Agents/pharmacology , Combined Modality Therapy/methods , Indoles/pharmacology , Liposomes/radiation effects , Neoplasms/therapy , Radiation-Sensitizing Agents/pharmacology , Tirapazamine/pharmacology , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/metabolism , Cell Line, Tumor , Drug Compounding/methods , Drug Liberation , Female , Hypoxia/pathology , Indoles/chemistry , Indoles/metabolism , Infrared Rays , Injections, Subcutaneous , Kinetics , Liposomes/administration & dosage , Liposomes/chemistry , Mammary Glands, Animal/metabolism , Mammary Glands, Animal/pathology , Mice , Neoplasms/pathology , Photochemotherapy/methods , Radiation-Sensitizing Agents/chemistry , Radiation-Sensitizing Agents/metabolism , Reactive Oxygen Species/agonists , Reactive Oxygen Species/metabolism , Tirapazamine/chemistry , Tirapazamine/metabolism , Tumor Burden/drug effects , Tumor Burden/radiation effectsABSTRACT
Catechin molecules such as epigallocatechin-3-gallate (EGCG) are capable of attenuating the biomolecular damage induced by UV radiation, possibly through molecular mechanisms involving the cell membranes. In this study, we confirmed the protective role of EGCG against UV of 1,2-dipalmitoyl-sn-glycero-3-[phospho-rac-(1-glycerol) (sodium salt) (DPPG) in liposomes and cast films. The incorporation of EGCG increased the stability of DPPG liposomes as indicated by UV-vis absorption spectra. Using 2D correlation spectroscopy to analyse the spectra, we found that DPPG and EGCG are co-helpers and complement each other against degradation induced by UV. At the molecular level, UV irradiation affects the phosphate and carbonyl groups of DPPG, in addition to triggering the oxidation and opening of the pyrogallol ring of EGCG. Since EGCG can be incorporated into liposomes and is a strong shield against UV radiation, one may envisage its use in anti-ageing and sunscreen creams, and in dermal drug delivery.
Subject(s)
Antioxidants/chemistry , Catechin/analogs & derivatives , Phosphatidylglycerols/chemistry , Radiation-Protective Agents/chemistry , Catechin/chemistry , Lipid Bilayers/chemistry , Lipid Bilayers/radiation effects , Liposomes/chemistry , Liposomes/radiation effects , Oxidation-Reduction , Principal Component Analysis , Ultraviolet RaysABSTRACT
Liposomes are very attractive membrane models and excellent drug delivery systems. Concerning their drug delivery aspects, the mixing liposomes with biocompatible copolymers allows for stability and the incorporation of several drugs. We developed PEG coated vesicles from the mixture of DPPC and F127 Pluronic copolymer to obtain long-circulating nanoparticles (mixed vesicles). We employed an innovative process previously developed by us: a small amount of F127 mixed in DPPC, thin film preparation, followed by hydration (lipids plus F127) using a bath sonicator cleaner type, forming unilamellar spherical vesicles with diameter â¼100 nm. The formed PEG coated vesicles were incorporated with the xanthene dye Erythrosine B (ERY), and its ester derivatives as photosensitizers (PS) for photodynamic proposes. The F127/DPPC mixed vesicles promoted a higher PS incorporation, and with better thermal and kinetic stability, at least 60 days, when compared to conventional DPPC liposome. The binding constant and quenching analysis revealed that with a higher PS hydrophobicity, PS affinity increases toward the nanoparticle and results in a deeper PS location inside the lipid bilayer. An increment in the fluorescence quantum yield was observed, while the PS singlet oxygen generations remained high. Dialysis studies demonstrated that PS were released based on their hydrophobicity. Permeation analysis showed that all PS can reach the deeper regions of the skin. The Decyl Ester derivative/nanoparticle exhibited high photoactivity against Caco-2 cancer cells (in vitro studies). The PEG coated from F127/DPPC mixed vesicles are very promising nanocarriers for erythrosine and its derivatives.
Subject(s)
Drug Delivery Systems/methods , Erythrosine/pharmacology , Liposomes/chemistry , Photosensitizing Agents/pharmacology , Skin/drug effects , 1,2-Dipalmitoylphosphatidylcholine/chemistry , Animals , Caco-2 Cells , Cell Line , Cell Survival/drug effects , Drug Compounding/methods , Ear , Erythrosine/analogs & derivatives , Erythrosine/chemistry , Esters , Fibroblasts/cytology , Fibroblasts/drug effects , Fibroblasts/metabolism , Humans , Hydrophobic and Hydrophilic Interactions , Light , Liposomes/metabolism , Liposomes/pharmacokinetics , Liposomes/radiation effects , Permeability , Photochemotherapy/methods , Photosensitizing Agents/chemistry , Poloxamer/chemistry , Polyethylene Glycols/chemistry , Singlet Oxygen/chemistry , Singlet Oxygen/metabolism , Skin/metabolism , Sonication , SwineABSTRACT
Light-driven nano/micromotors are attracting much attention, not only as molecular devices but also as components of bioinspired robots. In nature, several pathogens such as Listeria use actin polymerisation machinery for their propulsion. Despite the development of various motors, it remains challenging to mimic natural systems to create artificial motors propelled by fibre formation. Herein, we report the propulsion of giant liposomes driven by light-induced peptide nanofibre growth on their surface. Peptide-DNA conjugates connected by a photocleavage unit were asymmetrically introduced onto phase-separated giant liposomes. Ultraviolet (UV) light irradiation cleaved the conjugates and released peptide units, which self-assembled into nanofibres, driving the translational movement of the liposomes. The velocity of the liposomes reflected the rates of the photocleavage reaction and subsequent fibre formation of the peptide-DNA conjugates. These results showed that chemical design of the light-induced peptide nanofibre formation is a useful approach to fabricating bioinspired motors with controllable motility.
Subject(s)
Liposomes/chemistry , Movement/radiation effects , Nanofibers/chemistry , Peptides , Ultraviolet Rays , Biomimetics , DNA , Liposomes/radiation effects , PhotolysisABSTRACT
INTRODUCTION: Authors of numerous publications have proved the therapeutic effect of laser irradiation on biological material, but the mechanisms at cellular and subcellular level are not yet well understood. OBJECTIVE: The aim of this study was to assess the effect of laser radiation emitted by the MLS M1 system (Multiwave Locked System) at two wavelengths (808 nm continuous and 905 nm pulsed) on the stability and fluidity of liposomes with a lipid composition similar to that of human erythrocyte membrane or made of phosphatidylocholine. MATERIAL AND METHODS: Liposomes were exposed to low-energy laser radiation at surface densities 195 mW/cm2 (frequency 1,000 Hz) and 230 mW/cm2 (frequency 2,000 Hz). Different doses of radiation energy in the range 0-15 J were applied. The surface energy density was within the range 0.46 - 4.9 J/cm 2. RESULTS: The fluidity and stability of liposomes subjected to such irradiation changed depending on the parameters of radiation used. CONCLUSIONS: Since MLS M1 laser radiation, depending on the parameters used, affects fluidity and stability of liposomes with the lipid content similar to erythrocyte membrane, it may also cause structural and functional changes in cell membranes.
Subject(s)
Cell Membrane/radiation effects , Membrane Lipids/radiation effects , Erythrocytes/radiation effects , Humans , Lasers , Liposomes/chemistry , Liposomes/radiation effects , Low-Level Light Therapy/instrumentation , Membrane Fluidity/radiation effectsABSTRACT
The efficacy and toxicity of drugs depend not only on their potency but also on their ability to reach the target sites in preference to non-target sites. In this regards destabilization of delivery vehicles induced by light can be an effective strategy for enhancing drug delivery with spatial and temporal control. Herein we demonstrate that the photoinduced isomerization from closed (hydrophobic) to open isomeric form (hydrophilic) of a novel DHI encapsulated in liposome leads to potential light-controlled drug delivery vehicles. We have used steady state and picosecond resolved dynamics of a drug 8-anilino-1-naphthalenesulfonic acid ammonium salt (ANS) incorporated in liposome to monitor the efficacy of destabilization of liposome in absence and presence UVA irradiation. Steady state and picosecond resolved polarization gated spectroscopy including the well-known strategy of solvation dynamics and Förster resonance energy transfer; reveal the possible mechanism out of various phenomena involved in destabilization of liposome. We have also investigated the therapeutic efficacy of doxorubicin (DOX) delivery from liposome to cervical cancer cell line HeLa. The FACS, confocal fluorescence microscopic and MTT assay studies reveal an enhanced cellular uptake of DOX leading to significant reduction in cell viability (â¼40%) of HeLa followed by photoresponsive destabilization of liposome. Our studies successfully demonstrate that these DHI encapsulated liposomes have potential application as a smart photosensitive drug delivery system.
Subject(s)
Antineoplastic Agents/pharmacology , Doxorubicin/pharmacology , Drug Compounding/methods , Indolizines/metabolism , Liposomes/radiation effects , Anilino Naphthalenesulfonates/chemistry , Antineoplastic Agents/metabolism , Cell Line, Transformed , Cell Survival/drug effects , Cell Survival/radiation effects , Doxorubicin/metabolism , Drug Liberation , Female , Fluorescent Dyes/chemistry , HeLa Cells , Humans , Hydrophobic and Hydrophilic Interactions , Indolizines/chemistry , Keratinocytes/cytology , Keratinocytes/drug effects , Keratinocytes/metabolism , Keratinocytes/radiation effects , Kinetics , Liposomes/chemistry , Liposomes/metabolism , Photochemical Processes , Ultraviolet RaysABSTRACT
Photo-triggerable liposomes are considered nowadays as promising drug delivery devices due to their potential to release encapsulated drugs in a spatial and temporal manner. In this work, we have investigated the photopermeation efficiency of three photosensitizers (PSs), namely verteporfin, pheophorbide a and m-THPP when incorporated into liposomes with well-defined lipid compositions (SOPC, DOPC or SLPC). By changing the nature of phospholipids and PSs, the illumination of the studied systems was shown to significantly alter their lipid bilayer properties via the formation of lipid peroxides. The system efficiency depends on the PS/phospholipid association, and the ability of the PS to peroxidize acyl chains. Our results demonstrated the possible use of these three clinically approved (or under investigation) PSs as potential candidates for photo-triggerable liposome conception.