Droplet size dependency and spatial heterogeneity of lipid oxidation in whey protein isolate-stabilized emulsions.

Spatiotemporal assessment of lipid and protein oxidation is key for understanding quality deterioration in emulsified food products containing polyunsaturated fatty acids. In this work, we first mechanistically validated the use of the lipid oxidation-sensitive fluorophore BODIPY 665/676 as a semi-quantitative marker for local peroxyl radical formation. Next, we assessed the impact of microfluidic and colloid mill emulsification (respectively producing mono- and polydisperse droplets) on local protein and lipid oxidation kinetics in whey protein isolate (WPI)-stabilized emulsions. We further used BODIPY 581/591 C11 and CAMPO-AFDye 647 as colocalisation markers for lipid and protein oxidation. The polydisperse emulsions showed an inverse relation between droplet size and lipid oxidation rate. Further, we observed less protein and lipid oxidation occurring in similar sized droplets in monodisperse emulsions. This observation was linked to more heterogeneous protein packing at the droplet surface during colloid mill emulsification, resulting in larger inter-droplet heterogeneity in both protein and lipid oxidation. Our findings indicate the critical roles of emulsification methods and droplet sizes in understanding and managing lipid oxidation.

Designing Antitrypanosomal and Antileishmanial BODIPY Derivatives: A Computational and In Vitro Assessment.

Leishmaniasis and Human African trypanosomiasis pose significant public health threats in resource-limited regions, accentuated by the drawbacks of the current antiprotozoal treatments and the lack of approved vaccines. Considering the demand for novel therapeutic drugs, a series of BODIPY derivatives with several functionalizations at the meso, 2 and/or 6 positions of the core were synthesized and characterized. The in vitro activity against Trypanosoma brucei and Leishmania major parasites was carried out alongside a human healthy cell line (MRC-5) to establish selectivity indices (SIs). Notably, the meso-substituted BODIPY, with 1-dimethylaminonaphthalene (1b) and anthracene moiety (1c), were the most active against L. major, displaying IC50 = 4.84 and 5.41 µM, with a 16 and 18-fold selectivity over MRC-5 cells, respectively. In contrast, the mono-formylated analogues 2b and 2c exhibited the highest toxicity (IC50 = 2.84 and 6.17 µM, respectively) and selectivity (SI = 24 and 11, respectively) against T. brucei. Further insights on the activity of these compounds were gathered from molecular docking studies. The results suggest that these BODIPYs act as competitive inhibitors targeting the NADPH/NADP+ linkage site of the pteridine reductase (PR) enzyme. Additionally, these findings unveil a range of quasi-degenerate binding complexes formed between the PRs and the investigated BODIPY derivatives. These results suggest a potential correlation between the anti-parasitic activity and the presence of multiple configurations that block the same site of the enzyme.

Light-Responsive Pt(IV) Prodrugs with Controlled Photoactivation and Low Dark Toxicity.

Light-induced release of cisplatin from Pt(IV) prodrugs represents a promising approach for precise control over the antiproliferative activity of Pt-based chemotherapeutic drugs. This method has the potential to overcome crucial drawbacks of conventional cisplatin therapy, such as high general toxicity toward healthy organs and tissues. Herein, we report two Pt(IV) prodrugs with BODIPY-based photoactive ligands Pt-1 and Pt-2, which were designed using carbamate and triazole linkers, respectively. Both prodrugs demonstrated the ability to release cisplatin under blue light irradiation without the requirement of an external reducing agent. Dicarboxylated Pt-2 prodrug turned out to be more stable in the dark and more sensitive to light than its monocarbamate Pt-1 counterpart; these observations were explained using DFT calculations. The investigation of the photoreduction mechanism of Pt-1 and Pt-2 prodrugs using DFT modeling and ΔG0 PET estimation suggests that the photoinduced electron transfer from the singlet excited state of the BODIPY axial ligand to the Pt(IV) center is the key step in the light-induced release of cisplatin from the complexes. Cytotoxicity studies demonstrated that both prodrugs were nontoxic in the dark and toxic to MCF-7 cells under low-dose irradiation with blue light, and the observed effect was solely due to the cisplatin release from the Pt(IV) prodrugs. Our research presents an elegant synthetic approach to light-activated Pt(IV) prodrugs and presents findings that may contribute to the future rational design of photoactivatable Pt(IV) prodrugs.

Valency-based structural properties of gamma-sheet of boron clusters.

Boron cluster sheets are two-dimensional boron atom-based formations called borophene. They are similar to the two-dimensional sheet known as graphene, which is composed of carbon atoms arranged in a hexagonal lattice. The unique electrical, mechanical, and thermal properties of borophene make it a sought-after substance for a variety of uses, such as catalysis, energy storage, and electronics. There are two ways to manufacture borophene: chemical vapor deposition and molecular beam epitaxy. Vertex-edge valency-based topological descriptors are a great example of a molecular descriptor that provides information on the connection of atoms in a molecule. These descriptions are based on the notion that a node's value in a molecular network is the sum of the valency of those atoms that are directly connected to that node. In this article, we discussed some novel vertex-edge (ve) and edge-vertex (ev) topological descriptors and found their formulations for the boron cluster or borophene sheets. Also, we show the numerical and graphical comparison of these descriptors in this article.

Early Stage In Vitro Bioprofiling of Potential Low-Molecular-Weight Organoboron Compounds for Boron Neutron Capture Therapy (BNCT)-Proposal for a Guide.

Given the renewed interest in boron neutron capture therapy (BNCT) and the intensified search for improved boron carriers, as well as the difficulties of coherently comparing the carriers described so far, it seems necessary to define a basic set of assays and standardized methods to be used in the early stages of boron carrier development in vitro. The selection of assays and corresponding methods is based on the practical experience of the authors and is certainly not exhaustive, but open to discussion. The proposed tests/characteristics: Solubility, lipophilicity, stability, cytotoxicity, and cellular uptake apply to both low molecular weight (up to 500 Da) and high molecular weight (5000 Da and more) boron carriers. However, the specific methods have been selected primarily for low molecular weight boron carriers; in the case of high molecular weight compounds, some of the methods may need to be adapted.

Acid-Activated TAT Peptide-Modified Biomimetic Boron Nitride Nanoparticles for Enhanced Targeted Codelivery of Doxorubicin and Indocyanine Green: A Synergistic Cancer Photothermal and Chemotherapeutic Approach.

The evolution of nano-drug delivery systems addresses the limitations of conventional cancer treatments with stimulus-responsive nanomaterial-based delivery systems presenting temporal and spatial advantages. Among various nanomaterials, boron nitride nanoparticles (BNNs) demonstrate significant potential in drug delivery and cancer treatment, providing a high drug loading capacity, multifunctionality, and low toxicity. However, the challenge lies in augmenting nanomaterial accumulation exclusively within tumors while preserving healthy tissues. To address this, we introduce a novel approach involving cancer cell membrane-functionalized BNNs (CM-BIDdT) for the codelivery of doxorubicin (Dox) and indocyanine green to treat homologous tumor. The cancer cell membrane biomimetic CM-BIDdT nanoparticles possess highly efficient homologous targeting capabilities toward tumor cells. The surface modification with acylated TAT peptides (dTAT) further enhances the nanoparticle intracellular accumulation. Consequently, CM-BIDdT nanoparticles, responsive to the acidic tumor microenvironment, hydrolyze amide bonds, activate the transmembrane penetrating function, and achieve precise targeting with substantial accumulation at the tumor site. Additionally, the photothermal effect of CM-BIDdT under laser irradiation not only kills cells through thermal ablation but also destroys the membrane on the surface of the nanoparticles, facilitating Dox release. Therefore, the fabricated CM-BIDdT nanoparticles orchestrate chemo-photothermal combination therapy and effectively inhibit tumor growth with minimal adverse effects, holding promise as a new modality for synergistic cancer treatment.

BODIPY-based photocages: rational design and their biomedical application.

Photocages, also known as photoactivated protective groups (PPGs), have been utilized to achieve controlled release of target molecules in a non-invasive and spatiotemporal manner. In the past decade, BODIPY fluorophores, a well-established class of fluorescent dyes, have emerged as a novel type of photoactivated protective group capable of efficiently releasing cargo species upon irradiation. This is due to their exceptional properties, including high molar absorption coefficients, resistance to photochemical and thermal degradation, multiple modification sites, favorable uncaging quantum yields, and highly adjustable spectral properties. Compared to traditional photocages that mainly absorb UV light, BODIPY-based photocages that absorb visible/near-infrared (Vis/NIR) light offer advantages such as deeper tissue penetration and reduced bio-autofluorescence, making them highly suitable for various biomedical applications. Consequently, different types of photoactivated protective groups based on the BODIPY skeleton have been established. This highlight provides a comprehensive overview of the strategies employed to construct BODIPY photocages by substituting leaving groups at different positions within the BODIPY fluorophore, including the meso-methyl position, boron position, 2,6-position, and 3,5-position. Furthermore, the application of these BODIPY photocages in biomedical fields, such as fluorescence imaging and controlled release of active species, is discussed.

Directional Pumpless Transport of Biomolecules through Self-Propelled Nanodroplets on Patterned Heterostructures.

The surface patterning in natural systems has exhibited appreciable functional advantages for life activities, which serve as inspiration for the design of artificial counterparts to achieve functions such as directional liquid transport at the nanoscale. Here, we propose a patterned two-dimensional (2D) in-plane heterostructure with a triangle-shaped hexagonal boron nitride (hBN) track embedded in graphene nanosheets, which can achieve unidirectional and self-propelled transport of nanodroplets carrying various biomolecules such as DNA, RNA, and peptides. Our extensive MD simulations show that the wettability gradient on the patterned heterostructure can drive the motion of nanodroplet with an instantaneous acceleration, which also permits long-distance transport (>100 nm) at the microsecond time scale. The different behaviors of various types of biomolecules have been further studied systematically within the transporting nanodroplets. These findings suggest that these specially designed, patterned heterostructures have the potential for spontaneous, directional transport of important biomolecules, which might be useful in biosensing, drug delivery, and biomedical nanodevices.

Hexagonal Boron Nitride Quantum Dots Embedded on Layer-by-Layer Films for Peroxidase-Assisted Colorimetric Detection of ß-Galactosidase Producing Pathogens.

Pathogen detection has become a major research area all over the world for water quality surveillance and microbial risk assessment. Therefore, designing simple and sensitive detection kits plays a key role in envisaging and evaluating the risk of disease outbreaks and providing quality healthcare settings. Herein, we have designed a facile and low-cost colorimetric sensing strategy for the selective and sensitive determination of ß-galactosidase producing pathogens. The hexagonal boron nitride quantum dots (h-BN QDs) were established as a nanozyme that showed prominent peroxidase-like activity, which catalyzes 3,3',5,5'-tetramethylbenzidine (TMB) oxidation by H2O2. The h-BN QDs were embedded on a layer-by-layer assembled agarose biopolymer. The ß-galactosidase enzyme partially degrades ß-1,4 glycosidic bonds of agarose polymer, resulting in accessibility of h-BN QDs on the solid surface. This assay can be conveniently conducted and analyzed by monitoring the blue color formation due to TMB oxidation within 30 min. The nanocomposite was stable for more than 90 days and was showing TMB oxidation after incubating it with Escherichia coli (E. coli). The limit of detection was calculated to be 1.8 × 106 and 1.5 × 106 CFU/mL for E. coli and Klebsiella pneumonia (K. pneumonia), respectively. Furthermore, this novel sensing approach is an attractive platform that was successfully applied to detect E. coli in spiked water samples and other food products with good accuracy, indicating its practical applicability for the detection of pathogens in real samples.

BNCT pancreatic cancer treatment strategy with glucose-conjugated boron drug.

Multidisciplinary therapy centered on radical surgery for resectable pancreatic cancer is expected to prolong prognosis, but relies on CA19-9 biomarker levels to determine treatment strategy. Boron neutron capture therapy (BNCT) is a chemoradiotherapy using tumor hyperaccumulator boron drugs and neutron irradiation. The purpose of this study is to investigate novel boron drug agents for BNCT for pancreatic cancer. Bioinformatics was used to evaluate the uptake of current boron amino acid (BPA) drugs for BNCT into pancreatic cancer. The expression of the amino acid transporter LAT1, a BPA uptake transporter, was low in pancreatic cancer and even lower in high CA19-9 pancreatic cancer. In contrast, the glucose transporter was high in high CA19-9 pancreatic cancers and inversely correlated with LAT1 expression. Considering the low EPR effect in pancreatic cancer, we synthesized a small molecule Glucose-BSH, which is boron BSH bound to glucose, and confirmed its specific uptake in pancreatic cancer. uptake of Glucose-BSH was confirmed in an environment compatible with the tumor microenvironment. The therapeutic efficacy and safety of Glucose-BSH by therapeutic neutron irradiation were confirmed with BNCT. We report Glucose-BSH boron drug discovery study of a Precision Medicine BNCT with application to high CA19-9 pancreatic cancer.

Facile one-pot synthesis of Ir(III) Bodipy polymeric gemini nanoparticles for tumor selective NIR photoactivated anticancer therapy.

Over the last decades, a variety of metal complexes have been developed as chemotherapeutic agents. Despite the promising therapeutic prospects, the vast majority of these compounds suffer from low solubility, poor pharmacological properties, and most importantly poor tumor accumulation. To circumvent these limitations, herein, the incorporation of cytotoxic Ir(III) complexes and a variety of photosensitizers into polymeric gemini nanoparticles that selectively accumulate in the tumorous tissue and could be activated by near-infrared (NIR) light to exert an anticancer effect is reported. Upon exposure to light, the photosensitizer is able to generate singlet oxygen, triggering the rapid dissociation of the nanostructure and the activation of the Ir prodrug, thereby initiating a cascade of mitochondrial targeting and damage that ultimately leads to cell apoptosis. While selectively accumulating into tumorous tissue, the nanoparticles achieve almost complete eradication of the cisplatin-resistant cervical carcinoma tumor in vivo upon exposure to NIR irradiation.

Photodynamic-Assisted Electrochemiluminescence Enhancement toward Advanced BODIPY for Precision Diagnosis of Parkinson.

Nowadays, signal enhancement is imperative to increase sensitivity of advanced ECL devices for expediting their promising applications in clinic. In this work, photodynamic-assisted electrochemiluminescence (PDECL) device was constructed for precision diagnosis of Parkinson, where an advanced emitter was prepared by electrostatically linking 2,6-dimethyl-8-(3-carboxyphenyl)4,4'-difluoroboradiazene (BET) with 1-butyl-3-methylimidazole tetrafluoroborate ([BMIm][BF4]). Specifically, protoporphyrin IX (PPIX) can trigger the photodynamic reaction under light irradiation with a wavelength of 450 nm to generate lots of singlet oxygen (1O2), showing a 2.43-fold magnification in the ECL responses. Then, the aptamer (Apt) was assembled on the functional BET-[BMIm] for constructing a "signal off" ECL biosensor. Later on, the PPIX was embedded into the G-quadruplex (G4) of the Apt to magnify the ECL signals for bioanalysis of α-synuclein (α-syn) under light excitation. In the optimized surroundings, the resulting PDECL sensor has a broad linear range of 100.0 aM ∼ 10.0 fM and a low limit of detection (LOD) of 63 aM, coupled by differentiating Parkinson patients from normal individuals according to the receiver operating characteristic (ROC) curve analysis of actual blood samples. Such research holds great promise for synthesis of other advanced luminophores, combined with achieving an early clinical diagnosis.

Dynamic Imaging of Lipid Droplets in Cells and Tissues by Using Dioxaborine Barbiturate-Based Fluorogenic Probes.

Lipids are essential for various cellular functions, including energy storage, membrane flexibility, and signaling molecule production. Maintaining proper lipid levels is important to prevent health problems such as cancer, neurodegenerative disorders, cardiovascular diseases, obesity, and diabetes. Monitoring cellular lipid droplets (LDs) in real-time with high resolution can provide insights into LD-related pathways and diseases owing to the dynamic nature of LDs. Fluorescence-based imaging is widely used for tracking LDs in live cells and animal models. However, the current fluorophores have limitations such as poor photostability and high background staining. Herein, we developed a novel fluorogenic probe based on a push-pull interaction combined with aggregation-induced emission enhancement (AIEE) for dynamic imaging of LDs. Probe 1 exhibits favorable membrane permeability and spectroscopic characteristics, allowing specific imaging of cellular LDs and time-lapse imaging of LD accumulation. This probe can also be used to examine LDs in fruit fly tissues in various metabolic states, serving as a highly versatile and specific tool for dynamic LD imaging in cellular and tissue environments.

Development of Inhibitors, Probes, and PROTAC Provides a Complete Toolbox to Study PARK7 in the Living Cell.

The integration of diverse chemical tools like small-molecule inhibitors, activity-based probes (ABPs), and proteolysis targeting chimeras (PROTACs) advances clinical drug discovery and facilitates the exploration of various biological facets of targeted proteins. Here, we report the development of such a chemical toolbox for the human Parkinson disease protein 7 (PARK7/DJ-1) implicated in Parkinson's disease and cancers. By combining structure-guided design, miniaturized library synthesis, and high-throughput screening, we identified two potent compounds, JYQ-164 and JYQ-173, inhibiting PARK7 in vitro and in cells by covalently and selectively targeting its critical residue, Cys106. Leveraging JYQ-173, we further developed a cell-permeable Bodipy probe, JYQ-196, for covalent labeling of PARK7 in living cells and a first-in-class PARK7 degrader JYQ-194 that selectively induces its proteasomal degradation in human cells. Our study provides a valuable toolbox to enhance the understanding of PARK7 biology in cellular contexts and opens new opportunities for therapeutic interventions.

Effects of hexagonal boron nitride on mechanical properties of bone cement (Polymethylmethacrylate).

OBJECTIVES: The aim of this study was to investigate the effects of adding hexagonal boron nitride at four different concentrations to polymethylmethacrylate (PMMA) bone cement, which is commonly used in orthopedic surgeries, on the mechanical properties and microarchitecture of the bone cement. MATERIALS AND METHODS: The study included an unaltered control group and groups containing four different concentrations (40 g of bone cement with 0.5 g, 1 g, 1.5 g, 2 g) of hexagonal boron nitride. The samples used for mechanical tests were prepared at 20±2ºC in operating room conditions, using molds in accordance with the test standards. As a result of the tests, the pressure values at which the samples deformed were determined from the load-deformation graphs, and the megapascal (MPa) values at which the samples exhibited strength were calculated. RESULTS: The samples with 0.5 g boron added to the bone cement had significantly increased mechanical strength, particularly in the compression test. In the group where 2 g boron was added, it was noted that, compared to the other groups, the strength pressure decreased and the porosity increased. The porosity did not change particularly in the group where 0.5 g boron was added. CONCLUSION: Our study results demonstrate that adding hexagonal boron nitride (HBN) to bone cement at a low concentration (0.5 g / 40 g PPMA) significantly increases the mechanical strength in terms of MPa (compression forces) without adversely affecting porosity. However, the incorporation of HBN at higher concentrations increases porosity, thereby compromising the biomechanical properties of the bone cement, as evidenced by the negative impact on compression and four-point bending tests. Boron-based products have gained increased utilization in the medical field, and HBN is emerging as a promising chemical compound, steadily growing in significance.

Synthesis of Bodipy-Tagged Galactoconjugates and Evaluation of Their Antibacterial Properties.

As a development of our research on biocompatible glycoconjugate probes and specifically multi-chromophoric systems, herein, we report the synthesis and early bactericidal tests of two luminescent glycoconjugates whose basic structure is characterized by two boron dipyrromethene difluoride (BODIPY) moieties and three galactoside rings mounted on an oligophenylene ethynylene (OPE) skeleton. BODIPY fluorophores have found widespread application in many branches of biology in the last few decades. In particular, molecular platforms showing two different BODIPY groups have unique photophysical behavior useful in fluorescence imaging. Construction of the complex architecture of the new probes is accomplished through a convergent route that exploits a series of copper-free Heck-Cassar-Sonogashira cross-couplings. The great emergency due to the proliferation of bacterial infections, in conjunction with growing antibiotic resistance, requires the production of new multifunctional drugs and efficient methods for their targeted delivery to control bacteria-associated diseases. Preliminary studies of the glycoconjugate properties as antibacterial agents against representatives of Gram-negative (P. aeruginosa) and Gram-positive (S. aureus) pathogens, which are associated with chronic infections, indicated significant bactericidal activity ascribable to their structural features.

Narrow spectrum nano-antibiotic for selective removal of ARB from contaminated water: New insights into stimuli response based on cellular attachment, lysis, and excretion.

Narrow spectrum nano-antibiotics are supposedly the future trouble-shooters to improve the efficacy of conventional antimicrobials for treatment of severe bacterial infections, remove contamination from water and diminish the development of antibiotic resistance. In this study, antimicrobial peptide functionalized boron-carbon-nitride nanosheets ((Ant)pep@BCN NSs) are developed that are a promising wastewater disinfector and antibiotic resistant bactericide agent. These nanosheets are developed for selective removal and effective inactivation of antibiotic resistant bacteria (ARB) from water in presence of two virulent bacteria. The (Ant)pep@BCN NSs provide reactive surface receptors specific to the ARB. They mimic muralytic enzymes to damage the cell membrane of ARB. These NSs demonstrate 3-fold higher antimicrobial efficiency against the targeted ARB compared to pristine BCN even at lower concentrations. To the best of our knowledge, this is the first time that functionalized BCN has been developed to remove ARB selectively from wastewater. Furthermore, the (Ant)pep@BCN selectively reduced the microbiological load and led to morphological changes in Gram negative ARB in a mixed bacterial inoculum. These ARBs excreted outer-inner membrane vesicles (OIMVs) of triangular shape as a stimuli response to (Ant)pep@BCN NSs. These novel antimicrobial peptide-NSs have potential to improve treatment efficacy against ARB infections and water contamination.

Unplugging lateral fenestrations of NALCN reveals a hidden drug binding site within the pore region.

The sodium (Na+) leak channel (NALCN) is a member of the four-domain voltage-gated cation channel family that includes the prototypical voltage-gated sodium and calcium channels (NaVs and CaVs, respectively). Unlike NaVs and CaVs, which have four lateral fenestrations that serve as routes for lipophilic compounds to enter the central cavity to modulate channel function, NALCN has bulky residues (W311, L588, M1145, and Y1436) that block these openings. Structural data suggest that occluded fenestrations underlie the pharmacological resistance of NALCN, but functional evidence is lacking. To test this hypothesis, we unplugged the fenestrations of NALCN by substituting the four aforementioned residues with alanine (AAAA) and compared the effects of NaV, CaV, and NALCN blockers on both wild-type (WT) and AAAA channels. Most compounds behaved in a similar manner on both channels, but phenytoin and 2-aminoethoxydiphenyl borate (2-APB) elicited additional, distinct responses on AAAA channels. Further experiments using single alanine mutants revealed that phenytoin and 2-APB enter the inner cavity through distinct fenestrations, implying structural specificity to their modes of access. Using a combination of computational and functional approaches, we identified amino acid residues critical for 2-APB activity, supporting the existence of drug binding site(s) within the pore region. Intrigued by the activity of 2-APB and its analogues, we tested compounds containing the diphenylmethane/amine moiety on WT channels. We identified clinically used drugs that exhibited diverse activity, thus expanding the pharmacological toolbox for NALCN. While the low potencies of active compounds reiterate the pharmacological resistance of NALCN, our findings lay the foundation for rational drug design to develop NALCN modulators with refined properties.

Novel BODIPY-based nano-biomaterials with enhanced D-A-D structure for NIR-triggered photodynamic and photothermal therapy.

Near-infrared (NIR) responsive nanoparticles are an important platform for multimodal phototherapy. Importantly, the simultaneous NIR-triggered photodynamic (PDT) and photothermal (PTT) therapy is a powerful approach to increase the antitumor efficiency of phototherapic nanoparticles due to the synergistic effect. Herein, a boron dipyrromethene (BODIPY)-based amphiphilic dye with enhanced electron donor-acceptor-donor (D-A-D) structure (BDP-AP) was designed and synthesized, which could self-assemble into stable nanoparticles (BDP-AP NPs) for the synergistic NIR-triggered PDT/PTT therapy. BDP-AP NPs synchronously generated singlet oxygen (1O2) and achieved preeminent photothermal conversion efficiency (61.42%). The in vitro and in vivo experiments showed that BDP-AP NPs possessed negligible dark cytotoxicity and infusive anticancer performance. BDP-AP NPs provide valuable guidance for the construction of PDT/PTT-synergistic NIR nanoagents to improve the efficiency of photoinduced cancer therapy in the future.

Triplet-Triplet Annihilation Upconverting Liposomes: Mechanistic Insights into the Role of Membranes in Two-Dimensional TTA-UC.

Triplet-triplet annihilation upconversion (TTA-UC) implemented in nanoparticle assemblies is of emerging interest in biomedical applications, including in drug delivery and imaging. As it is a bimolecular process, ensuring sufficient mobility of the sensitizer and annihilator to facilitate effective collision in the nanoparticle is key. Liposomes can provide the benefits of two-dimensional confinement and condensed concentration of the sensitizer and annihilator along with superior fluidity compared to other nanoparticle assemblies. They are also biocompatible and widely applied across drug delivery modalities. However, there are relatively few liposomal TTA-UC systems reported to date, so systematic studies of the influence of the liposomal environment on TTA-UC are currently lacking. Here, we report the first example of a BODIPY-based sensitizer TTA-UC system within liposomes and use this system to study TTA-UC generation and compare the relative intensity of the anti-Stokes signal for this system as a function of liposome composition and membrane fluidity. We report for the first time on time-resolved spectroscopic studies of TTA-UC in membranes. Nanosecond transient absorption data reveal the BODIPY-perylene dyad sensitizer has a long triplet lifetime in liposome with contributions from three triplet excited states, whose lifetimes are reduced upon coinclusion of the annihilator due to triplet-triplet energy transfer, to a greater extent than in solution. This indicates triplet energy transfer between the sensitizer and the annihilator is enhanced in the membrane system. Molecular dynamics simulations of the sensitizer and annihilator TTA collision complex are modeled in the membrane and confirm the co-orientation of the pair within the membrane structure and that the persistence time of the bound complex exceeds the TTA kinetics. Modeling also reliably predicted the diffusion coefficient for the sensitizer which matches closely with the experimental values from fluorescence correlation spectroscopy. The relative intensity of the TTA-UC output across nine liposomal systems of different lipid compositions was explored to examine the influence of membrane viscosity on upconversion (UC). UC showed the highest relative intensity for the most fluidic membranes and the weakest intensity for highly viscous membrane compositions, including a phase separation membrane. Overall, our study reveals that the co-orientation of the UC pair within the membrane is crucial for effective TTA-UC within a biomembrane and that the intensity of the TTA-UC output can be tuned in liposomal nanoparticles by modifying the phase and fluidity of the liposome. These new insights will aid in the design of liposomal TTA-UC systems for biomedical applications.