Biology subjects

Zhen, Y.

Publications and source records attributed to Zhen, Y..

At least 19 recordsLinked to original sources

bioRxiv2026

Stepwise GRN co-option in the evolution of a dipteran respiratory organ

The origin of morphological novelty lies at the heart of evolutionary biology, yet how ecological shifts drive its emergence through rewiring of gene regulatory networks (GRNs) remains poorly understood. Here, we dissect the roles of GRN co-option in the development and evolution of the prothoracic respiratory organ (PROD), a key innovation facilitating aquatic respiration in dipteran pupae. Ancestral-state reconstruction across over 200 species reveals that PROD originated [~]241 Ma in the common ancestor of Diptera, with a major increase in structural complexity in schizophoran flies [~]66-70 Ma. These transitions coincide with the Carnian Pluvial Episode and the K-Pg mass extinction, periods of profound climatic and ecological upheaval that likely imposed selection pressure for efficient pupal gas exchange in flooded or submerged habitats. Using comparative transcriptomics, scRNA-seq, and genetic manipulations in Drosophila melanogaster and Aedes albopictus, we demonstrate that PROD is a prothoracic wing serial homolog, specified by a cut-centered spiracle GRN and arising through heterochronic activation of an appendage GRN. In schizophoran flies, increase in complexity of PROD involved additional co-option of a breathless-centered tracheal GRN. Our findings reveal a stepwise model of hierarchical GRN co-option and provide potential links between geo-climatic events to the origin and escalation of morphological novelty. This eco-evo-devo framework provides a mechanistic and generalizable paradigm for how ecological challenges are translated into morphological innovations over macroevolutionary timescales.

evolutionary biology↗

bioRxiv2025

When Animals Turn Inside Out: The Eversion of Bloodworms

Bloodworms, Glycera dibranchiata, possess an eversible proboscis that normally remains concealed within their bodies but explosively everts if the worm attacks or burrows. How does the bloodworm evert quickly and reliably? In a series of experiments, we characterize bloodworm kinematics, pressure, and material properties to estimate the criteria for eversion safely without rupture of the proboscis. We predict the proboscis can withstand pressures 50 times higher and bending strains up to three times higher than the respective values observed. We also present a dimensional analysis of eversion, finding that everting animals, from frogs to snails to sharks, do not satisfy Froudes law for equivalence of velocities. Our findings may help inspire the development of pressure-driven soft robots with efficient retraction capabilities.

biophysics↗

bioRxiv2025

A systematic comparison of cooperation and coordination across behavioural, psychological, and neural scales

Cooperation and coordination are the two fundamental mechanisms for enhancing social welfare. However, the intrinsic differences between the dynamics of cooperation and coordination remain elusive, particularly from an interpretable perspective that bridges behavioural, psychological, and neural scales. Here, we compare and analyze cooperation and coordination within a unified framework by assigning participants to an adjustable public goods game for iterated real-time interactions. By integrating model-free behavioural patterns and psychological intentions, we show that individuals are driven by increased flexibility and are more susceptible to peer influence in decision-making under cooperation. While under coordination, it is easier to reach the group consensus, inspiring individuals to stick more closely to their existing behavioural patterns and the default social norms. Furthermore, although peer punishment can enhance reciprocal contributions in all scenarios, the detailed impact and the resultant adverse phenomena (anti-social punishment) in cooperation and coordination are different. Notably, behavioural motive differences are also reflected in the neural responses recorded via fNIRS, in which coordination is associated with activation of the rTPJ and more consistent inter-brain synchronization in the dmPFC, while there is a negative correlation between dmPFC-rTPJ connectivity and contributions under cooperation. In addition, rTPJ during the punishment phase is significantly activated compared with the investment phase. Our study systematically reveals the fundamental differences between cooperation and coordination at the multi-scale levels, which not only deepens the understanding of reciprocal behaviour in social groups, but also provides a foundation for designing targeted incentive mechanisms.

animal behavior and cognition↗

bioRxiv2025

Aberrant Modular Dynamics of Functional Networks in Schizophrenia and Their Relationship with Neurotransmitter and Gene Expression Profiles

IntroductionNumerous studies have emphasized the time-varying modular architecture of functional brain networks and its relevance to cognitive functions in healthy participants. However, how brain modular dynamics change in schizophrenia and how these alterations relate to neurotransmitter and transcriptomic signatures have not been well elucidated. MethodsWe harmonized resting-state fMRI data from a multi-site sample including 223 patients and 279 healthy controls and applied the multilayer network method to estimate the regional module switching rate (flexibility) of functional brain connectomes. We examined aberrant flexibility in patients relative to controls and explored its relations to neurotransmitter systems and postmortem gene expression. ResultsCompared with controls, patients with schizophrenia had significantly higher flexibility in the somatomotor and right visual regions, and lower flexibility in the left parahippocampal gyrus, right supramarginal gyrus, right frontal-operculum-insula, bilateral precuneus posterior cingulate cortex, and bilateral inferior parietal gyrus. These alterations were associated with multiple neurotransmitter systems and weighted gene transcriptomic profiles. The most relevant genes were preferentially enriched for biological processes of transmembrane transport and brain development, specific cell types, and previously identified schizophrenia-related genes. ConclusionsThis study reveals aberrant modular dynamics in schizophrenia and its relations to neurotransmitter systems and schizophrenia-related transcriptomic profiles, providing insights into the understanding of the pathophysiology underlying schizophrenia.

neuroscience↗

bioRxiv2024

Sapphire-Based Optrode for Low Noise Neural Recording and Optogenetic Manipulation

Electrophysiological recordings of neurons in deep brain regions using optogenetic stimulation are essential to understanding and regulating the role of complex neural activity in biological behavior and cognitive function. Optogenetic techniques have significantly advanced neuroscience research by enabling the optical manipulation of neural activities. Because of the significance of the technique, constant advancements in implantable optrodes that integrate optical stimulation with low-noise, large-scale electrophysiological recording are in demand to improve the spatiotemporal resolution for various experimental designs and future clinical applications. However, robust and easy-to-use neural optrodes that integrate neural recording arrays with high-intensity light emitting diodes (LEDs) are still lacking. Here, we propose a neural optrode based on Gallium Nitride (GaN) on sapphire technology, which integrates a high-intensity blue LED with a 5x2 recording array monolithically for simultaneous neural recording and optogenetic manipulation. To reduce the noise interference between the recording electrodes and the LED, which is in close physical proximity, three metal grounding interlayers were incorporated within the optrode, and their ability to reduce LED-induced artifacts during neural recording was confirmed through both electromagnetic simulations and experimental demonstrations. The capability of the sapphire optrode to record action potentials has been demonstrated by recording the firing of mitral/tuft cells in the olfactory bulbs of mice in vivo. Additionally, the elevation of action potential firing due to optogenetic stimulation observed using the sapphire probe in medial superior olive (MSO) neurons of the gerbil auditory brainstem confirms the capability of this sapphire optrode to precisely access neural activities in deep brain regions under complex experimental designs.

neuroscience↗

bioRxiv2024

Generation of a biliary tract cancer cell line atlas reveals molecular subtypes and therapeutic targets

Biliary tract cancers (BTCs) are a group of deadly malignancies encompassing intrahepatic and extrahepatic cholangiocarcinoma, gallbladder carcinoma, and ampullary carcinoma. Here, we present the integrative analysis of 63 BTC cell lines via multi-omics clustering and genome- scale CRISPR screens, providing a platform to illuminate BTC biology and inform therapeutic development. We identify dependencies broadly enriched in BTC compared to other cancers as well as dependencies selective to the anatomic subtypes. Notably, cholangiocarcinoma cell lines are stratified into distinct lineage subtypes based on biliary or dual biliary/hepatocyte marker signatures, associated with dependency on specific lineage survival factors. Transcriptional analysis of patient specimens demonstrates the prognostic significance of these lineage subtypes. Additionally, we delineate strategies to enhance targeted therapies or to overcome resistance in cell lines with key driver gene mutations. Furthermore, clustering based on dependencies and proteomics data elucidates unexpected functional relationships, including a BTC subgroup with partial squamous differentiation. Thus, this cell line atlas reveals potential therapeutic targets in molecularly defined BTCs, unveils biologically distinct disease subtypes, and offers a vital resource for BTC research.

cancer biology↗

bioRxiv2024

De novo genome assembly of Myricaria laxiflora provides insights into its molecular mechanisms under flooding stress

M. laxiflora is an endangered plant distributed in the Yangtze River floodplain of China, which often suffers from flood hazards during its growth and development. Due to the lack of a reference genome for M. laxiflora, the molecular regulatory mechanism of its waterlogging stress remains unclear. Here, we report for the first time the high-quality reference genome of M. laxiflora by using HiFi sequencing and Hi-C. The total assembly size of the M. laxiflora genome was 1.29 Gb with a scaffold N50 size of 29.5 Mb. A total of 23,666 genes encoding proteins and 5,457 ncRNA were predicted in this reference genome. In the M. laxiflora genome, a total of 101 MylAP2/ERF genes were identified and divided into 5 subgroups. Many MeJA responsive elements, ABA responsive elements, and hypoxia responsive elements were found in the promoter regions of these MylAP2/ERF genes. Based on transcriptome data analysis, a total of 74 MylAP2/ERF genes can respond to flooding stress. Meanwhile, it was found that three genes (MylAP2/ERF49/78/91) which belong to the same branch with RAP2.2 gene exhibited different expression trends under flooding stress. Our results provide valuable information on the molecular regulatory mechanism of flooding stress in M. laxiflora.

plant biology↗

bioRxiv2024

The heritability and structural correlates of brain entropy

Brain entropy (BEN) quantifies the temporal complexity of spontaneous neural activity, which has been increasingly recognized as providing important insights into cognitive functions and psychiatric disorders. However, its heritability and structural underpinnings are not well understood. Here, we utilize sample entropy to calculate BEN in healthy young adults using resting-state fMRI from the Human Connectome Project. We show that BEN is significantly heritable in broad brain regions. Heritability estimates exhibit regional variability, with lower heritability in the limbic and subcortical networks than in other networks. We further relate BEN to structural features including surface area (SA), cortical myelination (CM), cortical thickness (CT), and subcortical volumes (SV). We find that BEN is negatively correlated with SA in most cortical regions, but is positively correlated with CM in the prefrontal cortex, lateral temporal lobe, precuneus, lateral parietal cortex, and cingulate cortex. Only a few cortical regions show significant correlations between BEN and CT. By decomposing correlations into genetic and environmental components, we observe that most of BEN-SA correlations are associated with shared genetic and environmental effects. BEN-CM correlations are mainly attributed to shared environmental effects. BEN-CT correlations are partly related to shared environmental effects. We find no significant associations between BEN and SV. Collectively, our work establishes the genetic basis and structural correlates of resting-state fMRI-based BEN, supporting its potential application as an endophenotype for psychiatric disorders.

neuroscience↗

bioRxiv2023

Brain structure-function relationships across the human lifespan based on network eigenmodes

While brain function is considered to be tightly supported by the underlying structure, the connectome-based link estimated by current models is relatively moderate, leaving the structure-function relationship an ongoing challenge in neuroscience. Here, by proposing a novel mapping method based on network eigendecomposition, we present a concise and strong correspondence between structure and function. We show that the explanation of functional connectivity can be significantly improved by incorporating interactions between different structural eigenmodes, highlighting the potential importance of collective, higher-order coupling patterns between structure and function. We also demonstrate the pronounced advantage of the present mapping in capturing individual-specific information, and apply it to assess individual differences of structure-function coupling across the lifespan. We find that structure-function liberality weakens with age, which is driven by the decreases in functional components that are less constrained by anatomy, while the magnitude of structure-aligned components is preserved. Our results contribute to a more refined understanding of structure-function coupling and how it evolves with age.

neuroscience↗

bioRxiv2023

The path to "femmes fatales": the evolution of toxin resistance in predatory fireflies.

Toxic cardiotonic steroids (CTS) act as a defense mechanism in many firefly species (Lampyridae) by inhibiting a crucial enzyme called Na+,K+-ATPase (NKA). While most fireflies produce these toxins internally, species of the genus Photuris acquire them from a surprising source: predation on other fireflies. The contrasting physiology of toxin exposure and sequestration between Photuris and other firefly genera suggests that distinct strategies may be required to prevent self-intoxication. Our study demonstrates that both Photuris and their firefly prey have evolved highly-resistant NKAs. Using an evolutionary analysis of the specific target of CTS (ATP) in fireflies, and gene-editing in Drosophila, we find that the initial steps towards resistance were shared among Photuris and other firefly lineages. However, the Photuris lineage subsequently underwent multiple rounds of gene duplication and neofunctionalization, resulting in the development of ATP paralogs that are differentially expressed and exhibit increasing resistance to CTS. In contrast, other firefly species have maintained a single copy. Our results implicate gene duplication as a facilitator in the transition of Photuris to its distinct ecological role as predator of toxic firefly prey. One-Sentence SummaryGene duplication and neofunctionalization distinguish firefly predators from their toxic firefly prey.

evolutionary biology↗

bioRxiv2023

Noise improves the association between effects of local stimulation and structural degree of brain networks

Stimulation to local areas remarkably affects brain activity patterns, which can be exploited to investigate neural bases of cognitive function and modify pathological brain statuses. There has been growing interest in exploring the fundamental action mechanisms of local stimulation. Nevertheless, how noise amplitude, an essential element in neural dynamics, influences stimulation-induced brain states remains unknown. Here, we systematically examine the effects of local stimulation by using a large-scale biophysical model under different combinations of noise amplitudes and stimulation sites. We demonstrate that noise amplitude nonlinearly and heterogeneously tunes the stimulation effects from both regional and network perspectives. Furthermore, by incorporating the role of the anatomical network, we show that the peak frequencies of unstimulated areas at different stimulation sites averaged across noise amplitudes are highly positively related to structural connectivity. Crucially, the association between the overall changes in functional connectivity as well as the alterations in the constraints imposed by structural connectivity with the structural degree of stimulation sites is nonmonotonically influenced by the noise amplitude, with the association increasing in specific noise amplitude ranges. Moreover, the impacts of local stimulation of cognitive systems depend on the complex interplay between the noise amplitude and average structural degree. Overall, this work provides theoretical insights into how noise amplitude and network structure jointly modulate brain dynamics during stimulation and introduces possibilities for better predicting and controlling stimulation outcomes. Author summaryDespite the extensive application of local stimulation in cognition research and disease treatments, how regional perturbations alter brain-wide dynamics has not yet been fully understood. Given that noninvasive stimulation is associated with changes in the signal-noise relationship, we assume that noise amplitude is one of the plausible factors modulating the stimulation effects. Using a whole-brain biophysical model under different stimulation sites and noise amplitudes, we explore the influence of noise amplitude on stimulation effects and, more importantly, the interplay between noise amplitude and network structure. From a regional perspective, noise amplitude reduces the peak frequencies in unstimulated areas during stimulation. Moreover, we find a high similarity between the noise-averaged peak frequency matrix and the structural network. From a network perspective, we show that the changes in functional connectivity are decreased by noise amplitude, while the alterations in structural constraints display nonmonotonic trends. Intriguingly, increasing the noise amplitude in specific ranges can improve the association between network-level effects and structural degree, promoting better predicting and controlling therapeutic performance. Finally, the behaviors of cognitive systems quantified by network-level effects are jointly modulated by the noise amplitude and average structural degree.

neuroscience↗

bioRxiv2022

Nimbolide Targets RNF114 to Induce the Trapping of PARP1 and Poly-ADP-Ribosylation-Dependent DNA Repair Factors

PARP1 is an abundant nuclear enzyme that is critically involved in DNA damage response. Its main enzymatic function is to catalyze a protein post-translational modification known as poly-ADP-ribosylation (PARylation). Despite the tremendous progresses of PARP1 inhibitors (PARPi) in the clinic, the basic mechanism of action of PARPi is poorly understood. Recent studies point to PARP1 trapping as a key factor driving the cytotoxic and immunomodulatory functions of PARPi. However, the molecular underpinnings of PARP1 trapping remain elusive. Here, using an unbiased, quantitative proteomic screen, we identified RING finger protein 114 (RNF114), as a PARylation-dependent, ubiquitin E3 ligase involved in DNA damage response. Upon sensing DNA damage, RNF114 was recruited, in a PAR-dependent manner, to the DNA lesions, where it specifically targeted PARylated-PARP1 for ubiquitin-proteasomal degradation. The blockade of this pathway interfered with the removal of PARP1 from the DNA damage site, leading to profound PARP1 trapping. We show that a natural product, Nimbolide, targeted RNF114 to block the degradation and removal of PARylated-PARP1 from DNA lesions. Unlike conventional PARPi, nimbolide treatment induced the trapping of both PARP1 and PARylation-dependent DNA repair factors. This unique mechanism of action of nimbolide translated into its superior cytotoxic effects against BRCA-deficient cancers. Furthermore, we demonstrated that, as a super trapper of both PARylated-PARP1 and PARylation-dependent DNA repair factors, nimbolide was able to overcome the intrinsic and acquired resistance to PARPi. Finally, we showed that nimbolide treatment activated innate immune signaling and was able to synergize with various cytotoxic agents. These results point to the exciting possibility of targeting homologous recombination-deficient cancers using nimbolide and its analogs.

cancer biology↗

bioRxiv2022

The specificity of different-distance connections in human structural connectomes

Brain structural connectomes underpin complex cognitive processes. To date, abundant organizational features have been distilled by network-based tools, including hubs, modules, and small-worldness. However, these features are often devoid of spatial characteristics which directly shape connection formation. By considering the spatial embedding of brain networks, we reveal the connection specificity, that is, the similarity of similar-distance connections and the dissimilarity of different-distance connections. It is induced by the whole-brain connection length distribution, allowing areas to send and receive diverse signals through different-distance connections. Based on it, areas functional repertoires are associated with their connection length profiles, and meanwhile, length dispersion and clustering coefficients can be integrated into a hierarchy whose age-related degeneration may be related to cognitive decline. These results construct a putative bridge between brain spatial, topological, and functional features, expanding our understanding of how different architectures complement and reinforce each other to achieve complicated brain functions.

neuroscience↗

bioRxiv2022

Enhanced brain structure-function tethering in transmodal cortex revealed by high-frequency eigenmodes

The brains structural connectome supports signal propagation between neuronal elements, shaping diverse coactivation patterns that can be captured as functional connectivity. While the link between structure and function remains an ongoing challenge, the prevailing hypothesis is that the structure-function relationship may itself be gradually decoupled along a macroscale functional gradient spanning unimodal to transmodal regions. However, this hypothesis is strongly constrained by the underlying models which may neglect requisite signaling mechanisms. Here, we transform the structural connectome into a set of orthogonal eigenmodes governing frequency-specific diffusion patterns and show that regional structure-function relationships vary markedly under different signaling mechanisms. Specifically, low-frequency eigenmodes, which are considered sufficient to capture the essence of the functional network, contribute little to functional connectivity reconstruction in transmodal regions, resulting in structurefunction decoupling along the unimodal-transmodal gradient. In contrast, high-frequency eigenmodes, which are usually on the periphery of attention due to their association with noisy and random dynamical patterns, contribute significantly to functional connectivity prediction in transmodal regions, inducing gradually convergent structure-function relationships from unimodal to transmodal regions. Although the information in high-frequency eigenmodes is weak and scattered, it effectively enhances the structure-function correspondence by 35% in unimodal regions and 56% in transmodal regions. Altogether, our findings suggest that the structure-function divergence in transmodal areas may not be an intrinsic property of brain organization, but can be narrowed through multiplexed and regionally specialized signaling mechanisms.

neuroscience↗

bioRxiv2021

Histone neutralization in a rat model of acute lung injury induced by double-hit lipopolysaccharide

BackgroundAcute respiratory distress syndrome (ARDS) remains a challenge because of its high morbidity and mortality. Circulation histones levels in ARDS patients were correlated to disease severity and mortality. This study examined the impact of histone neutralization in a rat model of acute lung injury (ALI) induced by a lipopolysaccharide (LPS) double-hit. MethodsSixty-eight male Sprague-Dawley rats were randomized to sham (N=8, received saline only) or LPS (N=60). The LPS double-hit consisted of a 0.8 mg/kg intraperitoneal injection followed after 16 hours by 5 mg/kg intra-tracheal nebulized LPS. The LPS group was then randomized into five groups: LPS only (N=12); LPS + 5, 25, or 100 mg/kg intravenous STC3141 every 8 hours (LPS+L, LPS+M, LPS+H, respectively, each N=12); or LPS + intraperitoneal dexamethasone 2.5 mg/kg every 24 hours for 56 hours (LPS+D, N=12) The animals were observed for 72 hours. ResultsLPS animals developed ALI as suggested by lower oxygenation, lung edema formation, and histological changes compared to the sham animals. Compared to the LPS group, LPS+H and +D animals had significantly lower circulating histone levels; only the LPS+D group had significantly lower bronchoalveolar lavage fluid (BALF) histone concentrations. The LPS+L, +M, +H and +D groups had improved oxygenation compared to the LPS group and the LPS+H and +D groups had a lower lung wet-to-dry ratio. All animals survived. ConclusionNeutralization of histone using STC3141, especially at high dose, had similar therapeutic effects to dexamethasone in this LPS double-hit rat ALI model, with significantly decreased circulating histone concentration, improved oxygenation, and decreased lung edema formation.

pharmacology and toxicology↗

bioRxiv2021

High-quality genome and methylomes illustrate features underlying evolutionary success of oaks

The genus Quercus, which emerged ~55 million years ago during globally warm temperatures, diversified into ~450 species. We present a high-quality de novo genome assembly of a California endemic oak, Quercus lobata, revealing features consistent with oak evolutionary success. Effective population size remained large throughout history despite declining since the early Miocene. Analysis of 39,373 mapped protein-coding genes outlined copious duplications consistent with genetic and phenotypic diversity, both by retention of genes created during the ancient{gamma} whole genome hexaploid duplication event and by tandem duplication within families, including the numerous resistance genes and also unexpected candidate genes for an incompatibility system involving multiple non-self-recognition genes. An additional surprising finding is that subcontext-specific patterns of DNA methylation associated with transposable elements reveal broadly-distributed heterochromatin in intergenic regions, similar to grasses (another highly successful taxon). Collectively, these features promote genetic and phenotypic variation that would facilitate adaptability to changing environments.

genomics↗

bioRxiv2021

Autism_genepheno: Text mining of gene-phenotypeassociations reveals new phenotypic profiles ofautism-associated genes

Autism is a spectrum disorder with wide variation in type and severity of symptoms. Understanding gene-phenotype associations is vital to unravel the disease mechanisms and advance its diagnosis and treatment. To date, several databases have stored a large portion of gene-phenotype associations which are mainly obtained from genetic experiments. However, a large proportion of gene-phenotype associations are still buried in the autism-related literature and there are limited resources to investigate autism-associated gene-phenotype associations. Given the abundance of the autism-related literature, we were thus motivated to develop Autism_genepheno, a text mining pipeline to identify sentence-level mentions of autism-associated genes and phenotypes in literature through natural language processing methods. We have generated a comprehensive database of gene-phenotype associations in the last five years autism-related literature that can be easily updated as new literature becomes available. We have evaluated our pipeline through several different approaches, and we are able to rank and select top autism-associated genes through their unique and wide spectrum of phenotypic profiles, which could provide a unique resource for the diagnosis and treatment of autism. The data resources and the Autism_genpheno pipeline are available at: https://github.com/maiziezhoulab/Autism_genepheno.

bioinformatics↗

bioRxiv2020

Enhanced Loading of Paclitaxel in Cationic Liposomes by Replacement of Oleoyl with Linoleoyl Lipid Tails with Benefits in Cancer Therapeutics from In Vitro Studies

Lipid-based carriers of the hydrophobic drug paclitaxel (PTX) are used in clinical trials as next-generation agents for cancer chemotherapy. Improving the loading capacity of these carriers requires enhanced PTX solubilization. We compared the solubility of PTX in cationic liposomes (CLs) with lipid tails containing one (oleoyl; C18:1 {Delta}9; DOTAP/DOPC) or two (linoleoyl; C18:2 {Delta}9; DLinTAP/DLinPC) cis double bonds with newly synthesized cationic DLinTAP (2,3-dilinoleoyloxypropyltrimethylammonium methylsufate). We used differential-interference-contrast microscopy to directly observe PTX crystal formation and generate kinetic phase diagrams representing the time-dependence of PTX solubility as a function of PTX content in the membrane. Replacing tails bearing one cis double bond (DO lipids) with those bearing two (DLin lipids) significantly increased PTX membrane solubility in CLs. Remarkably, 8 mol% PTX in DLinTAP/DLinPC CLs remained soluble for approximately as long as 3 mol% PTX (the membrane solubility limit which has been the focus of most previous fundamental studies and clinical trials) in DOTAP/DOPC CLs. The large increase in solubility is likely caused by enhanced molecular affinity between lipid tails and PTX upon replacement of oleoyl by linoleoyl tails, rather than by the transition in membrane structure from lipid bilayers to inverse cylindrical micelles observed in small-angle X-ray scattering. Importantly, the efficacy of PTX-loaded CLs against human prostate cancer (PC3) cells from measurements of the IC50 of PTX cytotoxicity was unaffected by changing the lipid tails, and toxicity of the CL carrier alone was negligible. Moreover, efficacy was approximately doubled against human melanoma (M21) cells for PTX-loaded DLinTAP/DLinPC over DOTAP/DOPC CLs. The findings demonstrate the potential of chemical modifications of the lipid tails to increase the PTX membrane loading well over the typically used 3 mol% while maintaining (and in some cases even increasing) the efficacy of CLs. The increased PTX solubility will aid the development of liposomal PTX carriers that require significantly less lipid to deliver a given amount of PTX, reducing side effects and costs.

biophysics↗