Advances in liposomes loaded with photoresponse materials for cancer therapy.

Cancer treatment is presently a significant challenge in the medical domain, wherein the primary modalities of intervention include chemotherapy, radiation therapy and surgery. However, these therapeutic modalities carry side effects. Photothermal therapy (PTT) and photodynamic therapy (PDT) have emerged as promising modalities for the treatment of tumors in recent years. Phototherapy is a therapeutic approach that involves the exposure of materials to specific wavelengths of light, which can subsequently be converted into either heat or Reactive Oxygen Species (ROS) to effectively eradicate cancer cells. Due to the hydrophobicity and lack of targeting of many photoresponsive materials, the use of nano-carriers for their transportation has been extensively explored. Among these nanocarriers, liposomes have been identified as an effective drug delivery system due to their controllability and availability in the biomedical field. By binding photoresponsive materials to liposomes, it is possible to reduce the cytotoxicity of the material and regulate drug release and accumulation at the tumor site. This article provides a comprehensive review of the progress made in cancer therapy using photoresponsive materials loaded onto liposomes. Additionally, the article discusses the potential synergistic treatment through the combination of phototherapy with chemo/immuno/gene therapy using liposomes.

Enhanced Stability of Oral Vitamin C Delivery: A Novel Large-Scale Method for Liposomes Production and Encapsulation through Dynamic High-Pressure Microfluidization.

In recent years, nanocarriers have been widely used as an effective solution for oral administration of pharmaceuticals. However, there is still an urgent need to speed up their translation to clinical practice. Cost-effective and industrially scalable methodologies are still needed. Herein, the production of vitamin C-loaded liposomes for nutraceutical purposes has been investigated and optimized by adopting a High-Pressure Homogenizer. Initially, the impact of process parameters on particles size, distributions, and morphology was explored. The findings document that the pressure and cycle manipulation allow for control over liposome size and polydispersity, reaching a maximum encapsulation efficiency exceeding 80%. This significantly improves the storage stability of vitamin C, as demonstrated by monitoring its antioxidant activity. Furthermore, the in vitro simulation of gastrointestinal digestion shows that liposomes could protect the active substance from damage and control its release in the gastrointestinal fluid. Thus, the whole nanodelivery system can contribute to enhancing vitamin C bioavailability. In conclusion, the results indicate that this innovative approach to producing vitamin C liposomes holds promise for clinical translation and industrial scale-up. Indeed, by utilizing food-grade materials and straightforward equipment, it is possible to produce stable and functional liposomes suitable for health products.

In Vitro Effects of Charged and Zwitterionic Liposomes on Human Spermatozoa and Supplementation with Liposomes and Chlorogenic Acid during Sperm Freezing.

Semen handling and cryopreservation induce oxidative stress that should be minimized. In this study, human semen was supplemented during cryopreservation with formulations of handmade liposomes and chlorogenic acid (CGA), an antioxidant compound. Zwitterionic (ZL), anionic (AL), and cationic (CL) liposomes were synthesized and characterized. Three aliquots of swim-up-selected sperm were incubated with ZL, AL, and CL (1:10,000), respectively. The percentages of sperm with progressive motility, high mitochondrial membrane potential (MMP; JC-1), double-stranded DNA (dsDNA acridine orange), and acrosome integrity (Pisum sativum agglutinin) were assessed. Then, human semen was frozen using both 1:10,000 ZL and CGA as follows: freezing medium/empty ZL (EL), freezing medium/empty ZL/CGA in the medium (CGA + EL), freezing medium/CGA loaded ZL (CGA), freezing medium (CTR). The same sperm endpoints were evaluated. ZL were the most tolerated and used for semen cryopreservation protocols. All the supplemented samples showed better endpoints versus CTR (p < 0.001). In particular, spermatozoa from the CGA and CGA + EL A samples showed increased motility, dsDNA, and acrosome integrity versus CTR and EL (p < 0.001; motility EL vs. CGA + EL p < 0.05). ZL and CGA can improve post-thaw sperm quality, acting on both cold shock effect management and oxidative stress. These findings open new perspectives on human and animal reproduction.

Spatiotemporal modeling of nano-delivered chemotherapeutics for synergistic microwave ablation cancer therapy.

BACKGROUND AND OBJECTIVE: The effectiveness of current microwave ablation (MWA) therapies is limited. Administration of thermosensitive liposomes (TSLs) which release drugs in response to heat has presented a significant potential for enhancing the efficacy of thermal ablation treatment, and the benefits of targeted drug delivery. However, a complete knowledge of the mechanobiological processes underlying the drug release process, especially the intravascular drug release mechanism and its distribution in response to MWA needs to be improved. Multiscale computational-based modeling frameworks, integrating different biophysical phenomena, have recently emerged as promising tools to decipher the mechanobiological events in combo therapies. The present study aims to develop a novel multiscale computational model of TSLs delivery following MWA implantation. METHODS: Due to the complex interplay between the heating procedure and the drug concentration maps, a computational model is developed to determine the intravascular release of doxorubicin from TSL, its transvascular transport into the interstitium, transport in the interstitium, and cell uptake. Computational models can estimate the interplays among liposome and drug properties, tumor perfusion, and heating regimen to examine the impact of essential parameters and to optimize a targeted drug delivery platform. RESULTS: Results indicated that the synergy of TSLs with MWA allows more localized drug delivery with lower side effects. The drug release rate and tumor permeability play crucial roles in the efficacy of TSLs during MWA treatment. The computational model predicted an unencapsulated drug lime around the ablated zone, which can destroy more cancer cells compared to MWA alone by 40%. Administration of TSLs with a high release rate capacity can improve the percentage of killed cancer cells by 24%. Since the heating duration in MWA is less than 15 min, the presented combination therapy showed better performance for highly permeable tumors. CONCLUSION: This study highlights the potential of the proposed computational framework to address complex and realistic scenarios in cancer treatment, which can serve as the future research foundation, including advancements in nanomedicine and optimizing the pair of TSL and MWA for both preclinical and clinical studies. The present model could be as a valuable tool for patient-specific calibration of essential parameters.

Liposomes as selenium nanocarriers for foliar application to wheat plants: A biofortification strategy.

In the present work, liposomes have been used as nanocarriers in the biofortification of wheat plants with selenium (Se) through foliar application. Liposomal formulations were prepared using 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and Phospholipon®90H (P90H) (average size <100 nm), loaded with different concentrations of inorganic Se (selenite and selenate) and applied twice to the plants in the stage of vegetative growth. Liposomes enhanced Se uptake by wheat plants compared to direct application. The highest Se enrichment was achieved using the phospholipid DPPC and a concentration of 1000 µmol·L-1 of Se without affecting the biomass, chlorophylls, carotenoids, and the concentration of mineral nutrients of the plants. The chemical speciation of Se in the plants was further investigated by X-ray absorption spectroscopy (XAS). The results from XAS spectra revealed that most of the inorganic Se was transformed to organic Se and that the use of liposomes influenced the proportion of C-Se-C over C-Se-Se-C species.

Ultrasonic-assisted extraction of grape seed procyanidins, preparation of liposomes, and evaluation of their antioxidant capacity.

The residue remaining after oil extraction from grape seed contain abundant procyanidins. An ultrasonic-assisted enzyme method was performed to achieve a high extraction efficiency of procyanidins when the optimal extraction conditions were 8 U/g of cellulase, ultrasound power of 200 W, ultrasonic temperature of 50 ℃, and ultrasonic reaction time of 40 min. The effects of free procyanidins on both radical scavenging activity and thermal stability at 40, 60, and 80 ℃ of the procyanidins-loaded liposomal systems prepared by the ultrasonic-assisted method were discussed. The presence of procyanidins at concentrations ranging from 0.02 to 0.10 mg/mL was observed to be effective at inhibiting lipid oxidation by 15.15 % to 69.70 % in a linoleic acid model system during reaction for 168 h, as measured using the ferric thiocyanate method. The procyanidins-loaded liposomal systems prepared by the ultrasonic-assisted method were characterized by measuring the mean particle size and encapsulation efficiency. Moreover, the holographic plots showed that the effect-response points of procyanidins combined with α-tocopherol in liposomes were lower than the addition line and 95 % confidence interval limits. At the same time, there were significant differences between the theoretical IC50add value and the experimental IC50mix value. The interaction index (γ) of all combinations was observed to be less than 1. These results indicated that there was a synergistic antioxidant effect between procyanidins combined with α-tocopherol, which will show promising prospects in practical applications. In addition, particle size differentiation and morphology agglomeration were observed at different time points of antioxidant activity determination (0, 48, 96 h).

Enhancement of hepatoprotective activity of limonin from citrus seeds against acetaminophen-induced liver injury by HSCCC purification and liposomal encapsulation.

Limonin is a natural tetracyclic triterpenoid compound in citrus seeds that presents hepatoprotective effects but is often discarded as agricultural waste because of its low content and low solubility. Herein, limonin with high purity (98.11%) from citrus seeds was obtained via purification by high-speed counter-current chromatography (HSCCC) and recrystallization. Limonin-loaded liposomes (Lip-LM) prepared by thin film hydration and high pressure homogenization method to enhance its solubility and hepatoprotective effect on APAP-induced liver injury (AILI). Lip-LM appeared as lipid nanoparticles under a transmission electron microscope, and showed well dispersed nano-scale size (69.04 ± 0.42 nm), high encapsulation efficiency (93.67% ± 2.51%), sustained release, fine stability. Lip-LM also exhibited significantly better hepatoprotective activity on AILI than free limonin in vivo. In summary, Lip-LM might be used as a potential hepatoprotective agent in the form of dietary supplement and provide an effective strategy to improve the potential value of citrus seeds.

Preparation Optimization and Immunological Activity Studies of Portulaca oleracea L. Polysaccharides Liposomes.

AIMS: This study combines traditional Chinese medicine polysaccharides with nanomaterials to enhance drug bioavailability and immunological activity. BACKGROUND: The study of polysaccharide preparation, structure identification, pharmacological activity, and mechanism of action is deepening, but the research combined with the new drug delivery system is relatively weak, so the application of polysaccharides is still facing great limitations. In order to prolong the action time of polysaccharides and improve their bioavailability, liposome has become the most promising delivery carrier. OBJECTIVES: The purpose of this study was to optimize the preparation process of Portulaca oleracea L. polysaccharides liposomes (POL-PL) and evaluate the immunoactivity in vitro. METHODS: POL-PL was prepared by reverse evaporation, and the preparation process was optimized using the response surface methodology. The characteristic analysis of POL-PL was detected by the indicators including morphology, particle size, zeta potential, encapsulation efficiency, release, and stability. The effects of POL-PL on the proliferation and immunological activity of mouse spleen lymphocytes and RAW264.7 cells were evaluated in vitro. RESULTS: POL-PL is highly homogeneous in morphology and particle size, and its sustained release improves the bioavailability of Portulaca oleracea L. polysaccharides (POL-P). Moreover, POL-PL treatment significantly enhanced the proliferation and phagocytic activity of RAW264.7 cells and increased the secretion of IL-6, TNF-α, IL-1ß, and NO. CONCLUSION: This study suggested that POL-PL were prepared successfully by reverse evaporation method, and POL-PL had immunoenhancing activity in vitro. The results provided a theoretical basis for further application of POL-PL.

Fructus Xanthii and Magnolia liliiflora Volatile Oils Liposomes-Loaded Thermosensitive in situ Gel for Allergic Rhinitis Management.

Purpose: The aim of the present study was to fabricate a Fructus Xanthii and Magnolia liliiflora volatile oils liposomes-loaded thermosensitive in situ gel (gel/LIP/volatile oil) for effectively treating allergic rhinitis via intranasal administration. Patients and Methods: Particle size, polymer dispersity index (PDI), entrapment effectiveness, and cumulative drug permeation of the developed liposomes were assessed. Then, a thermoreversible in situ gel was created using the liposomes loaded with volatile oils of Fructus Xanthii and Magnolia liliiflora. The effectiveness of this treatment for allergic rhinitis was confirmed by evaluating nasal symptoms, and hematological results, after injecting the formulation into the ovalbumin (OVA)-sensitized mice, we conducted hematoxylin-eosin staining (HE) and immunohistochemistry to evaluate the outcomes. The effects of the gel/LIP/volatile oil formulation for nasal delivery of volatile oil in the treatment of rhinitis were then assessed. Results: The average particle size was 95.1 ± 3.6 nm, and the encapsulation efficiencies of Fructus Xanthii and Magnolia liliiflora volatile oils were 70.42 ± 5.41% and 67.10 ± 6.08%, respectively. Drug loadings of Fructus Xanthii and Magnolia liliiflora volatile oils were 9.10 ± 0.98% and 16.10 ± 1.03%, respectively. The binary formulation produced a gel rapidly in the nasal cavity with a strong mucosal adherence at a temperature of delivering volatile oil to the nasal mucosa steadily and continuously. After nasal administration, the gel/LIP/volatile oil sustained the volatile oil delivery into the mucosa. In comparison to the monolithic formulations, the gel/LIP/volatile oil binary formulation exhibited superior performance in terms of drug delivery capability and pharmacodynamic effects. Conclusion: This binary preparation displayed the ability to deliver drugs to the nasal mucosa and exhibited positive pharmacodynamic effects in treating OVA-induced rhinitis in mice. As a result, it has the potential to serve as a delivery platform for Traditional Chinese medicine in the treatment of allergic rhinitis.

Characterization of Nanohybridosomes from Lipids and Spruce Homogenate Containing Extracellular Vesicles.

Introduction: Lipid nanovesicles associated with bioactive phytochemicals from spruce needle homogenate (here called nano-sized hybridosomes or nanohybridosomes, NSHs) were considered. Methods: We formed NSHs by mixing appropriate amounts of lecithin, glycerol and supernatant of isolation of extracellular vesicles from spruce needle homogenate. We visualized NSHs by light microscopy and cryogenic transmission electron microscopy and assessed them by flow cytometry, dynamic light scattering, ultraviolet-visual spectroscopy, interferometric light microscopy and liquid chromatography-mass spectrometry. Results: We found that the particles consisted of a bilayer membrane and a fluid-like interior. Flow cytometry and interferometric light microscopy measurements showed that the majority of the particles were nano-sized. Dynamic light scattering and interferometric light microscopy measurements agreed well on the average hydrodynamic radius of the particles Rh (between 140 and 180 nm), while the concentrations of the particles were in the range between 1013 and 1014/mL indicating that NSHs present a considerable (more than 25%) of the sample which is much more than the yield of natural extracellular vesicles (EVs) from spruce needle homogenate (estimated less than 1%). Spruce specific lipids and proteins were found in hybridosomes. Discussion: Simple and low-cost preparation method, non-demanding saving process and efficient formation procedure suggest that large-scale production of NSHs from lipids and spruce needle homogenate is feasible.

Effect of tumor heterogeneity on enhancing drug delivery to vascularized tumors using thermo-sensitive liposomes triggered by hyperthermia: A multi-scale and multi-physics computational model.

In this study, a novel multi-scale and multi-physics image-based computational model is introduced to assess the delivery of doxorubicin (Dox) loaded temperature-sensitive liposomes (TSLs) in the presence of hyperthermia. Unlike previous methodologies, this approach incorporates capillary network geometry extracted from images, resulting in a more realistic physiological tumor model. This model holds significant promise in advancing personalized medicine by integrating patient-specific tumor properties. The finite element method is employed to solve the equations governing intravascular and interstitial fluid flows, as well as the transport of therapeutic agents within the tissue. Realistic biological conditions and intricate processes like intravascular pressure, drug binding to cells, and cellular uptake are also considered to enhance the model's accuracy. The results underscore the significant impact of vascular architecture on treatment outcomes. Variation in vascular network pattern yielded changes of up to 38 % in the fraction of killed cells (FKCs) parameter under identical conditions. Pressure control of the parent vessels can also improve FKCs by approximately 17 %. Tailoring the treatment plan based on tumor-specific parameters emerged as a critical factor influencing treatment efficacy. For instance, changing the time interval between the administration of Dox-loaded TSLs and hyperthermia can result in a 48 % improvement in treatment outcomes. Additionally, devising a customized heating schedule led to a 20 % increase in treatment efficacy. Our proposed model highlights the significant effect of tumor characteristics and vascular network structure on the final treatment outcomes of the presented combination treatment.

Smart composite scaffold to synchronize magnetic hyperthermia and chemotherapy for efficient breast cancer therapy.

Combination of different therapies is an attractive approach for cancer therapy. However, it is a challenge to synchronize different therapies for maximization of therapeutic effects. In this work, a smart composite scaffold that could synchronize magnetic hyperthermia and chemotherapy was prepared by hybridization of magnetic Fe3O4 nanoparticles and doxorubicin (Dox)-loaded thermosensitive liposomes with biodegradable polymers. Irradiation of alternating magnetic field (AMF) could not only increase the scaffold temperature for magnetic hyperthermia but also trigger the release of Dox for chemotherapy. The two functions of magnetic hyperthermia and chemotherapy were synchronized by switching AMF on and off. The synergistic anticancer effects of the composite scaffold were confirmed by in vitro cell culture and in vivo animal experiments. The composite scaffold could efficiently eliminate breast cancer cells under AMF irradiation. Moreover, the scaffold could support proliferation and adipogenic differentiation of mesenchymal stem cells for adipose tissue reconstruction after anticancer treatment. In vivo regeneration experiments showed that the composite scaffolds could effectively maintain their structural integrity and facilitate the infiltration and proliferation of normal cells within the scaffolds. The composite scaffold possesses multi-functions and is attractive as a novel platform for efficient breast cancer therapy.

Sequentially Released Liposomes Enhance Anti-Liver Cancer Efficacy of Tetrandrine and Celastrol-Loaded Coix Seed Oil.

Background: A sequential release co-delivery system is an effective strategy to improve anti-cancer efficacy. Herein, multicomponent-based liposomes (TET-CTM/L) loaded with tetrandrine (TET) and celastrol (CEL)-loaded coix seed oil microemulsion (CTM) were fabricated, which showed synergistic anti-liver cancer activities. By virtue of Enhanced Permeability and Retention (EPR) effect, TET-CTM/L can achieve efficient accumulation at the tumor site. TET was released initially to repair abnormal vessels and decrease the fibroblasts, and CTM was released subsequently for eradication of tumor tissue. Methods: TEM (transmission electron microscopy) and DLS (dynamic light scattering) were adopted to characterize the TET-CTM/L. Flow cytometry was adopted to examine the cellular uptake and cytotoxicity of HepG2 cells. The HepG2 xenograft nude mice were adopted to evaluate the anti-tumor efficacy and systemic safety of TET-CTM/L. Results: TEM images of TET-CTM/L showed the structure of small particle size of CTM within large-size liposomes, indicating that CTM can be encapsulated in liposomes by film dispersion method. In in vitro studies, TET-CTM/L induced massive apoptosis toward HepG2 cells, indicating synergistic cytotoxicity against HepG2 cells. In in vivo studies, TET-CTM/L displayed diminished systemic toxicity compared to celastrol or TET used alone. TET-CTM/L showed the excellent potential for tumor-targeting ability in a biodistribution study. Conclusion: Our study provides a new strategy for combining anti-cancer therapy that has good potential not only in the treatment of liver cancer but also can be applied to the treatment of other solid tumors.

Ultrasound assisted extraction and liposome encapsulation of olive leaves and orange peels: How to transform biomass waste into valuable resources with antimicrobial activity.

Every year million tons of by-products and waste from olive and orange processing are produced by agri-food industries, thus triggering environmental and economic problems worldwide. From the perspective of a circular economy model, olive leaves and orange peels can be valorized in valuable products due to the presence of bioactive compounds such as polyphenols exhibiting beneficial effects on human health. The aqueous extracts of olive leaves and orange peels rich in phenolic compounds were prepared by ultrasound-assisted extraction. Both extracts were characterized in terms of yield of extraction, total phenolic content and antioxidant capacity; the polyphenolic profiles were deeper investigated by HPLC-MS analysis. Each extract was included in liposomes composed by a natural phospholipid, 1,2-dioleoyl-sn-glycero-3-phosphocholine,and cholesterol prepared according to the thin-layer evaporation method coupled with a sonication process. The antimicrobial activity of the extracts, free and loaded in liposomes, was investigated according to the broth macrodilution method against different strains of potential bacterial pathogenic species: Staphylococcus aureus (NCIMB 9518), Bacillus subtilis (ATCC 6051) and Enterococcus faecalis (NCIMB 775) as Gram-positive, while Escherichia coli (NCIMB 13302), Pseudomonas aeruginosa (NCIMB 9904) and Klebsiella oxytoca (NCIMB 12259) as Gram-negative. The encapsulation of olive leaves extract in liposomes enhanced its antibacterial activity against S. aureus by an order of magnitude.

Preparation of pectin-coated and chitosan-coated phenylethanoside liposomes: Studies on characterization, stability, digestion and release behavior.

In this paper, the effects of extrusion, ultrasound on physicochemical properties of liposomes were studied, and the liposomes were prepared by ethanol injection combined with extrusion-ultrasound. In addition, the quality of PhGs lips, pectin-coated PhGs lips (P-lips) and chitosan-coated PhGs lips (C-lips) was evaluated by the average particle size, encapsulation efficiency (EE) and other indicators, which indicated that the nanoparticles had been successfully prepared. Compared with extrusion or ultrasonic operation alone, the EEs of ethanol injection combined with extrusion-ultrasonic increased by 8 % and 18 % respectively. Subsequently, transmission electron microscopy, Fourier transform infrared spectroscopy and DSC thermal analysis showed that PhGs in PhGs lips may produce hydrogen bonding forces with phospholipids, and pectin and chitosan in P-lips and C-lips were not only coated on the surface of PhGs lips, but also might have some interaction between them. Cell experiments showed that PhGs lips, P-lips and C-lips can effectively improve the bioavailability of PhGs. In addition, the storage stability of P-lips and C-lips was not significantly improved compared to PhGs lips, but their digestive stability was significantly improved, and the final retention rate in simulated intestinal fluid was about 25 % higher than that of PhGs lips.

Activate the endogenous Cu2+ switch for Zn(DDC)2 liposomes conversion: Providing a safer and less toxic alternative in cancer therapy.

The ancient anti-alcohol drug disulfiram (DSF) has gained widespread attention for its highly effective anti-tumor effects in cancer treatment. Our previous studies have developed liposome of Cu (DDC)2 to overcome the limitations, like the poor water solubility. However, Cu (DDC)2 liposomes still have shown difficulties in severe hemolytic reactions at high doses and systemic toxicity, which have limited their clinical use. Therefore, this study aims to exploratively investigate the feasibility of using DSF or DDC in combination also can chelate Zn2+ to form zinc diethyldithiocarbamate (Zn (DDC)2). Furthermore, this study prepared stable and homogeneous Zn (DDC)2 liposomes, which were able to be released in the tumor microenvironment (TME). The released Zn (DDC)2 was converted to Cu (DDC)2 with the help of endogenous Cu2+-switch enriched in the TME, which has a higher stability constant compared with Zn (DDC)2. In other words, the Cu2+-switch is activated at the tumor site, completing the conversion of the less cytotoxic Zn (DDC)2 to the more cytotoxic Cu (DDC)2 for effective tumor therapy so that the Zn (DDC)2 liposomes in vivo achieved the comparable therapeutic efficacy and provided a safer alternative to Cu (DDC)2 liposomes in cancer therapy.

Anti-tumor therapy of glycyrrhetinic acid targeted liposome co-delivery of doxorubicin and berberine for hepatocellular carcinoma.

During the development of hepatocellular carcinoma (HCC), hepatic stellate cells undergo activation and transform into cancer-associated fibroblasts (CAFs) due to the influence of tumor cells. The interaction between CAFs and tumor cells can compromise the effectiveness of chemotherapy drugs and promote tumor proliferation, invasion, and metastasis. This study explores the potential of glycyrrhetinic acid (GA)-modified liposomes (lip-GA) as a strategy for co-delivery of berberine (Ber) and doxorubicin (Dox) to treat HCC. The characterizations of liposomes, including particle size, zeta potential, polydispersity index, stability and in vitro drug release, were investigated. The study evaluated the anti-proliferation and anti-migration effects of Dox&Ber@lip-GA on the Huh-7 + LX-2 cell model were through MTT and wound-healing assays. Additionally, the in vivo drug distribution and anti-tumor efficacy were investigated using the H22 + NIH-3T3-bearing mouse model. The results indicated that Dox&Ber@lip-GA exhibited a nanoscale particle size, accumulated specifically in the tumor region, and was efficiently taken up by tumor cells. Compared to other groups, Dox&Ber@lip-GA demonstrated higher cytotoxicity and lower migration rates. Additionally, it significantly reduced the deposition of extracellular matrix (ECM) and inhibited tumor angiogenesis, thereby suppressing tumor growth. In conclusion, Dox&Ber@lip-GA exhibited superior anti-tumor effects both in vitro and in vivo, highlighting its potential as an effective therapeutic strategy for combating HCC.

Pre-mixing of omega-3 fatty acid-containing liposomes enhances the drug release rate and therapeutic efficacy of anticancer drugs loaded in liposomes.

The therapeutic efficacy of anticancer drugs loaded in liposomes composed of rigid phosphatidylcholine (PC) is hindered by the limited release of these drugs at the tumor site, which in turn hampers delivery of the drug to its intracellular target. In an attempt to improve the therapeutic efficacy of liposomal anticancer drugs, we here explored the use of empty liposomes as "trigger" vehicles to induce drug release from drug-loaded liposomes through liposome-liposome interactions. Empty liposomes containing PC in which omega-3 fatty acids comprised both fatty acid strands (Omega-L) showed a triggering effect on drug release from doxorubicin (DOX)-loaded liposomes (Caelyx). The effectiveness of this triggered-release effect was dependent on the Omega-L composition as well as the mixing ratio of Omega-L to Caelyx. Cryo-TEM and differential calorimetry studies revealed that the Omega-L effect was associated with liposome-liposome interactions that led to loosened membrane packing and increased fluidity of Caelyx. In cultured cells, the intracellular/intranuclear DOX uptake and anticancer efficacy of Caelyx was greatly improved by Omega-L pre-mixing. Intravenous injection of rats with Caelyx, premixed with Omega-L, decreased the area under the plasma concentration-time curve from time zero to time infinity and increased clearance without significantly changing the mean residence time or terminal half-life of DOX compared with Caelyx alone. Ex vivo bioimaging showed that DOX fluorescence in tumors, but not in other organs, was significantly increased by Omega-L premixing. In the mouse xenograft model, premixing of Omega-L with Caelyx suppressed tumor growth 2.5-fold compared with Caelyx. Collectively, the data provide preliminary evidence that the Omega-L-triggered drug release that occurs before and after dosing, particularly at tumor site, improved the therapeutic efficacy of Caelyx. The simple approach described here could enhance the therapeutic value of Caelyx and other anticancer drug-loaded liposomes.

Transformation of Black Phosphorus through Lattice Reconstruction for NIR-II-Responsive Cancer Therapy.

The photothermal performance of black phosphorus (BP) in the near infrared (NIR)-II bio-window (1000-1500 nm) is low, which limits its biomedical applications. Herein, ultrasmall nickel phosphide quantum dots (Ni2 P QDs) are synthesized with BP quantum dots (BPQDs) as the template by topochemical transformation. The size of Ni2 P QDs is ≈3.5 nm, similar to that of BPQDs, whereas the absorption and photothermal conversion efficiency of Ni2 P QDs at 1064 nm (43.5%) are significantly improved compared with those of BPQDs. To facilitate in vivo applications, an Ni2 P QDs-based liposomal nano-platform (Ni2 P-DOX@Lipo-cRGD) is designed by incorporation of Ni2 P QDs and doxorubicin (DOX) into liposomal bilayers and the interior, respectively. The encapsulated DOX is responsively released from liposomes upon 1064-nm laser irradiation owing to the photothermal effect of Ni2 P QDs, and the drug release rate and amount are controlled by the light intensity and exposure time. In vivo, experiments show that Ni2 P-DOX@Lipo-cRGD has excellent tumor target capability and biocompatibility, as well as complete tumor ablation through the combination of photothermal therapy and chemotherapy. The work provides a new paradigm for the NIR-II transformation of nano-materials and may shed light on the construction of multifunctional nano-platforms for cancer treatment.

Biosynthesis, characterization, magnetic hyperthermia, and in vitro toxicity evaluation of quercetin-loaded magnetoliposome lipid bilayer hybrid system on MCF-7 breast cancer.

Novel biocompatible and effective hyperthermia (HT) treatment materials for breast cancer therapeutic have recently attracting researchers, because of their effective ablation of cancer cells and negligible damage to healthy cells. Magnetoliposome (MLs) have numerous possibilities for utilize in cancer treatment, including smart drug delivery (SDD) mediated through alternating magnetic fields (AMF). In this work, magnesium ferrite (MgFe2O4) encapsulated with liposomes lipid bilayer (MLs), Quercetin (Q)-loaded MgFe2O4@Liposomes (Q-MLs) nano-hybrid system were successfully synthesized for magnetic hyperthermia (MHT) and SDD applications. The hybrid system was well-investigated by different techniques using X-ray diffraction (XRD), Fourier transforms infrared spectroscopy (FT-IR), Energy dispersive X-ray (EDX), Vibrating sample magnetometer (VSM), Transmission electron microscope (TEM), and Zeta Potential (ZP). The characterization results confirmed the improving quercetin-loading on the MLs surface. TEM analysis indicated the synthesized MgFe2O4, MLs, and Q-MLs were spherical with an average size of 23.7, 35.5, and 329.5 nm, respectively. The VSM results revealed that the MgFe2O4 exhibit excellent and effective saturation magnetization (MS) (40.5 emu/g). Quercetin drug loading and entrapment efficiency were found to be equal to 2.1 ± 0.1% and 42.3 ± 2.2%, respectively. The in-vitro Q release from Q-loaded MLs was found 40.2% at pH 5.1 and 69.87% at pH 7.4, verifying the Q-loading pH sensitivity. The MLs and Q-MLs hybrid system as MHT agents exhibit specific absorption rate (SAR) values of 197 and 205 W/g, correspondingly. Furthermore, the Q-MLs cytotoxicity was studied on the MCF-7 breast cancer cell line, and the obtained data demonstrated that the Q-MLs have a high cytotoxicity effect compared to MLs and free Q.