Search Results (3,622)

Background/Objectives: Hyperthermia coupled with temperature-triggered drug delivery systems, including drug-loaded thermosensitive liposomes, that exhibit increased membrane permeability at hyperthermia-relevant temperatures is a promising therapeutic strategy for cancer treatment. Our previous study revealed that nitrogen-doped carbon dots (CD) partially interact with the phospholipids of liposomes, increasing the membrane permeability of an encapsulated anticancer drug. In vitro cell experiments indicated that their presence in the culture medium, albeit at relatively high concentrations, also affect cell membrane permeability, enhancing drug internalization in cancer cells. This study aims to introduce either hydrophilic or lipophilic carbon dots into liposomes and evaluate them as thermosensitive drug delivery systems. Methods: Alkylated carbon dots (CD-C16) were synthesized and liposomal systems with either the lipophilic CD-C16 or the parent hydrophilic CD were prepared and efficiently loaded with doxorubicin (DOX). Following physicochemical characterization, their thermosensitivity was studied vs. time and temperature, while their effect on cell survival at 37 and 40 °C was evaluated against HEK293 and PC3 cells. Results: At 40 °C, for CD containing liposomes 50% DOX release is observed, whereas for CD-C16 containing liposomes 95% DOX is released within 5 min. Against PC3 cells at 40 °C, both DOX-loaded CD containing liposomes and CD-C16 containing liposomes are more potent compared to the parent drug-loaded liposomes, whereas CD-C16 containing liposomes are equally potent to free DOX. Against HEK293 cells the thermosensitive formulations at 40 °C prove even more cytotoxic, with CD-C16 containing liposomes being more potent than free DOX, but CD containing liposomes are advantageous for being less toxic than free DOX at 37 °C. Conclusions: Although work is needed to elucidate the mechanism at the molecular level, the results suggest that it is possible to adjust liposomal membrane permeability through the incorporation of carbon dots in order to optimize performance for hyperthermia-based applications. Full article

Cancer remains a major global health challenge, characterized by abnormal cell growth and metastasis. Current limitations of conventional therapies, particularly non-specific toxicity harming healthy cells, highlight the need for more targeted approaches. Nanotechnology offers a revolutionary solution, utilizing nanoparticles (NPs) for precise drug delivery to tumor sites while minimizing off-target effects. These nanometer-scale particles enable superior binding to cancer cell membranes, the tumor microenvironment, or nuclear receptors, facilitating significantly higher local concentrations of therapeutic agents. NPs, synthesized via physical, chemical, or biological methods, are categorized as organic (organic material-based) or inorganic (metallic particle-based). Key delivery mechanisms include the Enhanced Permeability and Retention (EPR) effect and Active Transport and Retention (ATR). This review specifically examines NP applications for the most prevalent cancers in the US (2025): breast, prostate, and lung. Gold and magnetic NPs show significant promise for early breast cancer detection. For lung cancer, polymeric NPs like PCL, PLA, and PLGA are effective carriers for peptides, proteins, and nucleic acids. BIND-014, a docetaxel-loaded NP formulation, represents an emerging strategy for prostate cancer. Clinically established examples include liposomal doxorubicin and albumin-bound paclitaxel. We comprehensively discuss the synthesis methods, delivery mechanisms, and the current landscape of NPs in research and clinical trials for these cancers. This analysis underscores the potential of nanotechnology to provide more effective and targeted therapeutic options for cancer patients in the future. A distinctive feature of this review is its comparative cancer-specific analysis of NP platforms in breast, prostate, and lung cancers. Unlike previous generalized reviews, this work integrates synthesis strategies, delivery mechanisms, translational challenges, and clinically relevant formulations to provide a bench-to-bedside perspective on the future of nanomedicine in oncology. Full article

Boron neutron capture therapy (BNCT) is a binary targeted radiotherapy that uses boron agents to treat refractory malignancies. This study developed a novel boronophenylalanine (BPA)-loaded liposome doped with o-carborane (CB) for BNCT. We applied response surface methodology (RSM) to identify factors affecting BPA loading and optimized encapsulation efficiency (EE) to minimize BPA loss. In in vitro experiments, these liposomes demonstrated promising characteristics for BNCT. The nanoparticle properties of CB-BPA-Lips remain stable for at least 48 h, and CB-BPA-Lips can effectively reduce the release of the agents loaded within them. Both cell viability assays and apoptosis assays have shown that CB-BPA-Lips have good biocompatibility and a lower inhibitory effect on cell viability than BPA. Cellular boron uptake peaked at 47.3642 ng B/10⁶ cells in A549 lung cancer cells and peaked at 38.8875 ng B/10⁶ cells in Bronchial Epithelium transformed with Ad12-SV40 2B (BEAS-2B) human normal bronchial epithelial cells at 24 h post-treatment, with both exceeding uptake in the BPA control group. Overall, this work presents an optimized liposomal formulation that enhances boron delivery to cancer cells and provides a potential candidate boron agent for BNCT pending in-depth in vivo studies. Full article

The utilization of immunomodulatory nanomaterials, i.e., leveraging their unique properties to enhance immune responses, represents a transformative approach for the treatment of various diseases. Recent advancements in nanotechnology have enabled the design of nanomaterials capable of delivering immunomodulatory agents in a targeted manner, such as cytokines, antibodies, and nucleic acids, to specific cells or tissues involved in immune regulation. These nanomaterials, including nanoparticles, liposomes, nanogels, nanoemulsions, dendrimers, MXenes and extracellular vesicles, have been increasingly tailored to modulate immune responses with precision and efficacy. This targeted approach not only enhances therapeutic outcomes but also reduces off-target effects, minimizing systemic toxicity. In this review, an overview of immunomodulatory nanomaterials and their biomedical applications are highlighted. Herein, we have discussed different types of nanomaterials and their design strategies, interactions with different immune system components (macrophages, dendritic cells (DCs), neutrophils, T lymphocytes (CD4⁺ helper T-cells, CD8⁺ cytotoxic T-cells, regulatory T-cells/Tregs, and memory T-cells), and B lymphocytes), and immunomodulation mechanisms. Furthermore, nanomaterial-based immunomodulation strategies to enhance cancer immunotherapy, wound healing, and bone regeneration and the treatment of infectious diseases, autoimmune diseases, and allergy and are discussed in detail. In addition to therapeutic applications, selected nanomaterial platforms demonstrate significant potential in pharmaceutical formulations by improving drug stability, controlled release, and bioavailability, as well as in cosmetology through skin-targeted delivery, anti-inflammatory activity, immune protection, and enhanced tissue regeneration. Finally, clinical trial updates, challenges and future prospects are outlined. Key findings indicate that lipid-based, polymeric, inorganic nanoparticles and dendrimers provide complementary advantages for immunomodulation, including efficient delivery, controlled release, multifunctionality, and precise immune targeting. Despite safety, regulatory, and scalability challenges, these systems show strong potential for advancing precision and personalized medicine. Taken together, these innovations hold great promise for personalized medicine approaches, wherein nanomaterials can be tailored to individual patient profiles for more effective and precise disease treatment and prevention strategies. This review focuses primarily on the mechanistic interactions between immunomodulatory nanomaterials and immune cells, including macrophages, dendritic cells, neutrophils, T lymphocytes, and B lymphocytes, rather than providing an exhaustive treatment of physicochemical optimization parameters such as particle size or surface modification chemistry, which fall outside the defined scope of this work. Full article

Targeted delivery systems offer a promising approach for selectively modulating cellular processes; yet the intracellular consequences of targeted nutrient delivery to trophoblast cells remain poorly defined. Here, we investigated a previously validated placenta-targeting peptide conjugated to liposomes encapsulating stable isotope-labelled L-arginine and L-lysine to examine cellular uptake and downstream molecular responses in a trophoblast-like cell model. Peptide-dependent uptake of fluorescently labelled liposomes was confirmed in BeWo cells, demonstrating selective internalisation compared with non-targeted controls. Encapsulation of isotope-labelled amino acids enabled direct quantification of intracellular delivery and incorporation into the cellular proteome using stable isotope labelling by amino acids in cell culture (SILAC). Quantitative proteomic analysis revealed coordinated changes in proteins associated with translation, metabolism, and nitric oxide synthase regulation following targeted liposomal uptake. Notably, V-type proton ATPase subunit G1 (ATP6V1G1) and large neutral amino acid transporter small subunit 1 (SLC7A5) showed increased incorporation of labelled amino acids and were independently validated by Western blotting. Together, these findings establish a proof-of-concept platform for targeted intracellular amino acid delivery to trophoblast-like cells and define the resulting proteomic responses. This work provides mechanistic insight into intracellular amino acid utilisation and a framework for future studies in placental cell biology. Full article

Wound healing research has advanced through nanotechnology-based delivery systems that enhance the stability and therapeutic potential of bioactive compounds. Resveratrol, a natural polyphenol with antioxidant and anti-inflammatory properties, shows promise for wound healing but is limited by poor bioavailability. This study investigates the efficacy of nano-liposome-encapsulated resveratrol in enhancing skin wound repair in adult zebrafish (Danio rerio). Using a laser-based ablation method, precise full-thickness skin wounds were induced and monitored over 50 days. Resveratrol-loaded liposomes were prepared and orally administered via gavage to facilitate systemic exposure. Compared to the control and blank liposome groups, resveratrol liposome treatment significantly accelerated wound closure, achieving earlier healing milestones (25%, 50%, and 75%). The zebrafish model provided a regenerative platform for real-time evaluation of nanomedicine-based therapies. This study demonstrates the wound healing effects of resveratrol and liposomal encapsulation, offering a targeted, systemically administered strategy for advanced systemic healing and highlighting zebrafish as a valuable model for preclinical regenerative medicine research. Full article

The neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) have emerged as potent modulators of immune responses during sepsis, yet their roles remain complex, alternating between protective and permissive depending on timing, tissue compartment, and inflammatory context. This review presents a historical assessment of VIP and PACAP in sepsis research, highlighting the evolution of conceptual advances across five decades. Starting in the 1980s, early studies revealed that VIP levels rise during endotoxemia and correlated with hypotension and mortality, suggesting a deleterious role. By the 1990s, research pivoted toward understanding gut-derived VIP and its interaction with nitric oxide, culminating in the classification of VIP and PACAP as “macrophage deactivating factors” that downregulate TNFα and IL-6. The 2000s further clarified their cell-specific actions through VPAC1/2 and PAC1 receptors, showing anti-inflammatory effects on both innate and adaptive immune cells, while illuminating delivery challenges overcome by liposomal encapsulation. The 2010s expanded this narrative by dissecting receptor dynamics, gut barrier regulation, and VIP’s role in neuroimmune crosstalk and thrombo-inflammation. Most recently, studies in the 2020s provide a nuanced view of how VIP suppresses inflammatory damage but also enables pathogen persistence during live bacterial infection, implicating VIP signaling in trade-offs between tolerance and clearance. Across this chronological framework, VIP and PACAP have oscillated between friend, foe, and frenemy, underscoring the importance of context in leveraging their therapeutic potential in sepsis. Full article

The clinical utility of the anticancer drug camptothecin (CPT) is limited by its poor aqueous solubility and instability in the bloodstream, hindering bioavailability and efficacy. This study explores the complexation of CPT with carboxymethyl-beta-cyclodextrin (cmβCD) to overcome these limitations. Fluorescence spectroscopy and molecular modeling demonstrated 1:1 inclusion complexes, with stability constants governed by electrostatic interactions that were inversely correlated with pH. To validate this effect, a cationic amino-beta-cyclodextrin (amβCD) was used as a mechanistic control, revealing that Coulombic forces significantly modulate binding strength and stoichiometry. Crucially, cmβCD enhanced CPT solubility by up to 11-fold at 14 × 10⁻³ moldm⁻³, enabling a 385-fold increase in drug loading into liposomal carriers compared to the cyclodextrin-free system. Fluorescence-based release studies indicated high liposomal stability at physiological pH and partial CPT release under acidic conditions. Furthermore, CPT-loaded liposomes demonstrated cytotoxicity against cancer cell lines, particularly BT-474, with IC₅₀ values generally comparable to or slightly higher than those of free CPT and the CPT:cmβCD complex, likely due to the distinct lysosomal cellular uptake pathway. This work highlights cmβCD complexation as a promising strategy to enhance CPT solubility and liposomal loading for improved drug delivery. Full article

Extracellular vesicles (EVs) are promising biomarkers for liquid biopsy, but their clinical application is limited by intrinsic heterogeneity and the lack of methods capable of resolving functionally distinct EV subpopulations at the single-vesicle level. Conventional bulk analyses obscure rare but clinically relevant EV subsets, while most single-EV approaches focus on physical properties or surface markers, with limited access to intravesicular functional information. Here, we report a fusion-enabled EV detection strategy at the single-particle level for functional profiling of macrophage-derived EVs. Liposomal probes encapsulating L-arginine, NADPH, and a nitric oxide (NO)-responsive fluorescent dye are engineered to fuse with EV membranes, delivering substrates into the vesicle lumen. In macrophage-derived EVs, inducible nitric oxide synthase (iNOS) catalyzes NO production, activating the fluorescent probe and generating a localized signal within individual vesicles. Signal generation is confined to vesicle-restricted reactions, ensuring specificity and minimizing background. The formation of hybrid vesicles further facilitates optical detection using conventional fluorescence microscopy. Full article

Lactase enzyme-based products experience challenges including residual lactose that result in lactose intolerance. The purpose of this study was to develop polyelectrolyte polysaccharide-enriched lactase-encapsulated liposomal hydrogel films as an edible coating of Perline Mozzarella cheese that delivers enzymes along with the product on the side of absorption in the small intestine. Coatings were investigated for shelf-life enhancement and in vitro enzyme release behaviour. Two different polymeric hydrogel film formulations were evaluated: lactase-encapsulated liposome-enriched chitosan (PCLLa) and lactase-encapsulated liposome-enriched polyelectrolyte chitosan and sodium alginate (CLLA). Lactase-encapsulated liposomes (mean particle size: 176 nm) were produced using 20% v/v lactase enzyme and 8% w/v lecithin using probe sonication. The edible hydrogel film coatings were applied on Perline Mozzarella cheese using the standard dip-coating method. Shelf-life characteristics of all samples were evaluated using pH, colour change, dry matter determination, microbial evaluation, and sensory analysis. CLLA coatings increased shelf life up to 60 days, displaying a pH of 5.48, continued normal colour, enhanced humidity balance, minimal bacterial growth, and the highest scores for sensory values when compared to both PCLLa (coatings) and the bare cheese substrate (control) samples. Furthermore, CLLA coatings provided greater stability for liposomes within the polyelectrolyte polymeric edible hydrogel film structure. Hence, the combination of liposomes with polyelectrolyte edible hydrogel films provides a novel strategy to enhance lactase enzyme encapsulation (for intolerance), stability, and delivering ability to the small intestine as well as improving the shelf life of coated cheese products. Full article

Background/Objectives: This study addresses the need for scalable and predictive strategies linking mixing conditions to nanocarrier properties by developing and analyzing a coaxial jet antisolvent process for the continuous production of pharmaceutical nanocarriers. Methods: A single experimental platform was used to generate both curcumin-based nanoparticles and nanoliposomes, enabling direct comparison of how mixing regime and formulation variables influence product characteristics. Results: Fluid-dynamic behavior was first characterized using tracer and micromixing experiments, revealing a strong dependence of mixing time on flow conditions, with characteristic mixing times decreasing from >1000 ms under laminar conditions to approximately 10–30 ms in turbulent regimes. Nanoparticles and liposomes obtained under optimized conditions exhibited mean sizes in the range of 120–250 nm, with polydispersity indices typically below 0.2 under optimized turbulent conditions. To rationalize these observations, a computational framework was implemented, combining Reynolds-averaged computational fluid dynamics with a population balance formulation solved by the method of moments. The model provided spatially resolved insight into solvent exchange, supersaturation development, and nucleation–growth dynamics, showing good agreement with experimental trends and capturing the effect of mixing conditions on particle size across different regimes. Conclusions: Although simplified, the modeling approach establishes the basis for future extensions toward full population-balance distribution simulations capable of predicting complete particle size distributions, highlighting the ability of the coaxial jet mixer to control supersaturation and particle formation through tunable hydrodynamic conditions. This capability makes the system particularly attractive compared to conventional batch or less controllable mixing technologies, enabling a more rational and scalable design of pharmaceutical nanocarriers, with good encapsulation performance as discussed in the main text. Full article

Background/Objectives: Peritoneal micrometastases (micromets) remain a major barrier to durable cytoreduction in ovarian and other intra-abdominal cancers because lesions are difficult to visualize and are often resistant to systemic therapy. Liposomal doxorubicin (Dox) improves pharmacokinetics but can be limited by slow intratumoral release. Porphyrin-phospholipid (PoP) liposomes enable near-infrared light–triggered release of Dox (chemophototherapy (CPT)), creating an opportunity for intraoperative fluorescence-guided treatment planning and monitoring. Here, we evaluate a laparoscopic fluorescence imaging platform for quantifying light-triggered drug delivery. Methods: LC-Dox-PoP was applied to SCC2095sc and SKOV-3 cultures in 2D monolayers and 3D spheroid clusters. Dox fluorescence was quantified using a laparoscopic fluorescence imaging system over 1–9 μg/mL concentrations and compared with standard well-plate reader measurements. Porphyrin fluorescence was monitored to assess spheroid localization and photobleaching after activation light exposure. Results: For both cell lines, Dox fluorescence exhibited an approximate 4-fold increase at the maximum administered LC-Dox-PoP concentration, following a linear trend in both SCC2095sc and SKOV-3 cultures (R² = 0.97, 0.98 for 2D and R² = 0.98, 0.98 for spheroids). Laparoscope-derived fluorescence measurements agreed with well-plate reader measurements (R² = 0.89–0.96). Porphyrin fluorescence provided stronger complementary contrast for localizing spheroid constructs and decreased after activation light exposure, consistent with photobleaching during triggered release. Conclusions: These results support a quantitative imaging framework for fluorescence-guided monitoring of light-triggered liposomal drug release and may enable individualized CPT dosimetry for peritoneal micrometastases. Findings in SCC2095sc additionally suggest potential relevance of fluorescence-guided CPT for head and neck/oral cancer, where localized post-resection adjuvant treatment may improve control of residual disease. Full article

Nanosomes—lipid vesicles at the nanoscale—enable the encapsulation of both hydrophilic and lipophilic actives and are increasingly used as skin delivery systems in cosmetic products. Alongside nanoemulsions, polymer nanocapsules, and inorganic nanoparticles (e.g., TiO₂, ZnO, Ag), they can enhance solubility, stability, residence time, and local bioavailability while enabling controlled release. This review summarizes nanocarrier structures, preparation concepts, and skin penetration pathways (transepidermal intercellular/transcellular and transappendageal), and discusses formulation factors that modulate delivery. We highlight applications in UV protection, anti-aging, and fragrance retention, focusing on lipid-based systems (liposomes/nanosomes, ethosomes, niosomes). Safety considerations are critically appraised with reference to EU and FDA frameworks, including physicochemical characterization, dermal penetration, irritation/sensitization, and genotoxicity testing. While most data indicate limited penetration through intact skin for particles ≥20 nm, enhanced uptake may occur under specific conditions (very small size, barrier impairment, mechanical stress), warranting careful risk assessment. We conclude with regulatory and sustainability perspectives and outline research priorities for long-term toxicology, in-use exposure, and standardization of methods. Full article

Although medicinal plants possess vast biological properties, crude medicinal plant extracts often show limited therapeutic efficacy due to poor aqueous solubility, instability, and inadequate bioavailability, which restricts efficient intracellular delivery. As cancer is a genetic disease requiring intracellular and nuclear targeting, improved delivery systems are essential. Warburgia salutaris is traditionally used in Southern Africa and possesses reported anticancer and anti-inflammatory properties; however, its crude extracts exhibit suboptimal delivery characteristics. This study comparatively evaluated the anticancer effects of unencapsulated (WSN) and liposomal-encapsulated (WSE) crude leaf extracts, with emphasis on apoptotic mechanisms. Liposomal formulation was confirmed by FTIR, PXRD, and DLS, yielding stable nanoparticles (159.4 nm; PDI 0.114; +79.3 mV). Both WSN and WSE demonstrated efficacy and concentration-dependent cytotoxicity against MCF-7 breast cancer cells (IC₅₀ < 0.0195 mg/mL) with minimal toxicity toward Vero kidney cells and RAW 264.7 macrophages. Mechanistically, WSN induced rapid cytotoxicity with necrotic features, whereas WSE promoted regulated apoptosis. Apoptosis was validated by DAPI/PI staining, Annexin V/PI flow cytometry, mRNA expression levels of Bax, Bcl-2, and caspase-3 measured with RT-PCR and proteome profiling array, confirming activation of intrinsic and extrinsic pathways. Both extracts also reduced LPS-induced ROS production. LC-MS identified multiple bioactive phytochemicals. Overall, liposomal encapsulation enhanced therapeutic precision, stability, and selectivity cytotoxicity, supporting its development as a nanomedicine-based anticancer strategy. Full article

Breakthrough invasive fungal infections (bIFIs) are a challenging serious complication in high-risk hematologic patients and allogeneic hematopoietic stem cell transplantation recipients that may negatively impact their outcome. Despite advances in antifungal prophylaxis, diagnostics, and supportive care, bIFI occurrence reflects a complex interaction between host immunosuppression, emergence of resistant pathogens and pharmacological variables, including subtherapeutic drug exposure. Candida spp. have shifted towards non-albicans yeasts, whereas breakthrough mold infections more frequently involve non-fumigatus Aspergillus, Mucorales, Fusarium spp., and Scedosporium/Lomentospora spp. Early clinical recognition, rapid therapy escalation, aggressive diagnostic investigation, a switch to liposomal amphotericin B-based regimens in patients on azole prophylaxis, and therapeutic drug monitoring are essential to improve outcomes. Reducing the growing global burden of bIFIs will also require improved access to high-quality diagnostics and strengthened educational and stewardship efforts that prioritize antifungal resistance as an urgent health concern. Full article