Proof-of-Concept Multistage Biomimetic Liposomal DNA Origami Nanosystem for the Remote Loading of Doxorubicin.
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ABSTRACT:
SUBMITTER: Palazzolo S
PROVIDER: S-EPMC6466551 | biostudies-literature | 2019 Apr
REPOSITORIES: biostudies-literature
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Project description:BackgroundAcute myeloid leukemia (AML) showed limited clinical therapeutic efficiency with chemotherapy for its multi-distributed lesions and hard-to-kill leukemia cells deep in the bone marrow.ResultsHere, a biomimetic nanosystem (DR@PLip) based on platelet membrane (PM) coating and doxorubicin (DOX)/ginsenoside (Rg3) co-loading was developed to potentiate the local-to-systemic chemoimmunotherapy for AML. The PM was designed for long-term circulation and better leukemia cells targeting. The participation of Rg3 was proved to enhance the tumor sensitivity to DOX, thus initiating the anti-tumor immune activation and effectively combating the leukemia cells hiding in the bone marrow.ConclusionsIn conclusion, the strategy that combining immediate chemotherapy with long-term immunotherapy achieved improved therapeutic efficiency and prolonged survival, which provided a new perspective for the clinical treatment of AML.
| S-EPMC9195256 | biostudies-literature
Project description:DNA origami systems could be important candidates for clinical applications. Unfortunately, their intrinsic properties such as the activation of non-specific immune system responses leading to inflammation, instability in physiological solutions, and a short in vivo lifetime are the major challenges for real world applications. A compact short tube DNA origami (STDO) of 30 nm in length and 10 nm in width was designed to fit inside the core of a stealth liposome (LSTDO) of about 150 nm to remote load doxorubicin. Biocompatibility was tested in three-dimensional (3D) organoid cultures and in vivo. Efficacy was evaluated in different cell lines and in a xenograft breast cancer mouse model. As described in a previous work, LSTDO is highly stable and biocompatible, escaping the recognition of the immune system. Here we show that LSTDO have an increased toleration in mouse liver organoids used as an ex vivo model that recapitulate the tissue of origin. This innovative drug delivery system (DDS) improves the antitumoral efficacy and biodistribution of doxorubicin in tumor-bearing mice and decreases bone marrow toxicity. Our application is an attractive system for the remote loading of other drugs able to interact with DNA for the preparation of liposomal formulations.
| S-EPMC6966502 | biostudies-literature
Project description:The combination of paclitaxel (PTX) and doxorubicin (DOX) has been widely used in the clinic. However, it remains unsatisfied due to the generation of severe toxicity. Previously, we have successfully synthesized a prodrug PTX-S-DOX (PSD). The prodrug displayed comparable in vitro cytotoxicity compared with the mixture of free PTX and DOX. Thus, we speculated that it could be promising to improve the anti-cancer effect and reduce adverse effects by improving the pharmacokinetics behavior of PSD and enhancing tumor accumulation. Due to the fact that copper ions (Cu2+) could coordinate with the anthracene nucleus of DOX, we speculate that the prodrug PSD could be actively loaded into liposomes by Cu2+ gradient. Hence, we designed a remote loading liposomal formulation of PSD (PSD LPs) for combination chemotherapy. The prepared PSD LPs displayed extended blood circulation, improved tumor accumulation, and more significant anti-tumor efficacy compared with PSD NPs. Furthermore, PSD LPs exhibited reduced cardiotoxicity and kidney damage compared with the physical mixture of Taxol and Doxil, indicating better safety. Therefore, this novel nano-platform provides a strategy to deliver doxorubicin with other poorly soluble antineoplastic drugs for combination therapy with high efficacy and low toxicity.
| S-EPMC7564015 | biostudies-literature
Project description:Previously we have developed and statistically validated Quantitative Structure Property Relationship (QSPR) models that correlate drugs' structural, physical and chemical properties as well as experimental conditions with the relative efficiency of remote loading of drugs into liposomes (Cern et al., J. Control. Release 160 (2012) 147-157). Herein, these models have been used to virtually screen a large drug database to identify novel candidate molecules for liposomal drug delivery. Computational hits were considered for experimental validation based on their predicted remote loading efficiency as well as additional considerations such as availability, recommended dose and relevance to the disease. Three compounds were selected for experimental testing which were confirmed to be correctly classified by our previously reported QSPR models developed with Iterative Stochastic Elimination (ISE) and k-Nearest Neighbors (kNN) approaches. In addition, 10 new molecules with known liposome remote loading efficiency that were not used by us in QSPR model development were identified in the published literature and employed as an additional model validation set. The external accuracy of the models was found to be as high as 82% or 92%, depending on the model. This study presents the first successful application of QSPR models for the computer-model-driven design of liposomal drugs.
| S-EPMC4165646 | biostudies-literature
Project description:BackgroundRemote photoplethysmography (rPPG) can record vital signs (VSs) by detecting subtle changes in the light reflected from the skin. Lifelight (Xim Ltd) is a novel software being developed as a medical device for the contactless measurement of VSs using rPPG via integral cameras on smart devices. Research to date has focused on extracting the pulsatile VS from the raw signal, which can be influenced by factors such as ambient light, skin thickness, facial movements, and skin tone.ObjectiveThis preliminary proof-of-concept study outlines a dynamic approach to rPPG signal processing wherein green channel signals from the most relevant areas of the face (the midface, comprising the cheeks, nose, and top of the lip) are optimized for each subject using tiling and aggregation (T&A) algorithms.MethodsHigh-resolution 60-second videos were recorded during the VISION-MD study. The midface was divided into 62 tiles of 20×20 pixels, and the signals from multiple tiles were evaluated using bespoke algorithms through weighting according to signal-to-noise ratio in the frequency domain (SNR-F) score or segmentation. Midface signals before and after T&A were categorized by a trained observer blinded to the data processing as 0 (high quality, suitable for algorithm training), 1 (suitable for algorithm testing), or 2 (inadequate quality). On secondary analysis, observer categories were compared for signals predicted to improve categories following T&A based on the SNR-F score. Observer ratings and SNR-F scores were also compared before and after T&A for Fitzpatrick skin tones 5 and 6, wherein rPPG is hampered by light absorption by melanin.ResultsThe analysis used 4310 videos recorded from 1315 participants. Category 2 and 1 signals had lower mean SNR-F scores than category 0 signals. T&A improved the mean SNR-F score using all algorithms. Depending on the algorithm, 18% (763/4212) to 31% (1306/4212) of signals improved by at least one category, with up to 10% (438/4212) improving into category 0, and 67% (2834/4212) to 79% (3337/4212) remaining in the same category. Importantly, 9% (396/4212) to 21% (875/4212) improved from category 2 (not usable) into category 1. All algorithms showed improvements. No more than 3% (137/4212) of signals were assigned to a lower-quality category following T&A. On secondary analysis, 62% of signals (32/52) were recategorized, as predicted from the SNR-F score. T&A improved SNR-F scores in darker skin tones; 41% of signals (151/369) improved from category 2 to 1 and 12% (44/369) from category 1 to 0.ConclusionsThe T&A approach to dynamic region of interest selection improved signal quality, including in dark skin tones. The method was verified by comparison with a trained observer's rating. T&A could overcome factors that compromise whole-face rPPG. This method's performance in estimating VS is currently being assessed.Trial registrationClinicalTrials.gov NCT04763746; https://clinicaltrials.gov/ct2/show/NCT04763746.
| S-EPMC10131655 | biostudies-literature
Project description:Photodynamic therapy (PDT) offers an alternative for cancer treatment by using ultraviolet or visible light in the presence of a photosensitizer and molecular oxygen, which can produce highly reactive oxygen species that ultimately leading to the ablation of tumor cells by multifactorial mechanisms. However, this technique is limited by the penetration depth of incident light, the hypoxic environment of solid tumors, and the vulnerability of photobleaching reduces the efficiency of many imaging agents. In this work, we reported a cellular level dual-functional imaging and PDT nanosystem BMEPC-loaded DNA origami for photodynamic therapy with high efficiency and stable photoreactive property. The carbazole derivative BMEPC is a one- and two-photon imaging agent and photosensitizer with large two-photon absorption cross section, which can be fully excited by near-infrared light, and is also capable of destroying targets under anaerobic condition by generating reactive intermediates of Type I photodynamic reactions. However, the application of BMEPC was restricted by its poor solubility in aqueous environment and its aggregation caused quenching. We observed BMEPC-loaded DNA origami effectively reduced the photobleaching of BMEPC within cells. Upon binding to DNA origami, the intramolecular rotation of BMEPC became proper restricted, which intensify fluorescence emission and radicals production when being excited. After the BMEPC-loaded DNA origami are taken up by tumor cells, upon irradiation, BMEPC could generate free radicals and be released due to DNA photocleavage as well as the following partially degradation. Apoptosis was then induced by the generation of free radicals. This functional nanosystem provides an insight into the design of photosensitizer-loaded DNA origami for effective intracellular imaging and photodynamic therapy.
| S-EPMC4837698 | biostudies-literature
Project description:Currently there are significant amounts of natural gas that cannot be produced and treated to meet pipeline specifications, because that would not be economically viable. This work investigates a bench scale multistage fluidized bed (MSFB) with shallow beds for sour gas removal from natural gas using a commercially available supported amine sorbent. A MSFB is regarded as a promising adsorber type for deep sour gas removal to parts per million concentrations. A series of experiments was conducted using carbon dioxide as sour gas and nitrogen to mimic natural gas. Removal below 3 mol ppm was successfully demonstrated. This indicates that gas bypassing is minor (that is, good gas-solid contacting) and that apparent adsorption kinetics are fast for the amine sorbent applied. Tray efficiencies for a chemisorption/adsorption system were reported for one of the first times. Current experiments performed at atmospheric pressure strongly indicate that deep removal is possible at higher pressures in a multistage fluidized bed.
| S-EPMC5871343 | biostudies-literature
Project description:Bone infections are a key health challenge with dramatic consequences for affected patients. In dentistry, periodontitis is a medically compromised condition for efficient dental care and bone grafting, the success of which depends on whether the surgical site is infected or not. Present treatments involve antibiotics associated with massive bacterial resistance effects, urging for the development of alternative antibacterial strategies. In this work, we established a safe-by-design bone substitute approach by combining bone-like apatite to peroxide ions close to natural in vivo oxygenated species aimed at fighting pathogens. In parallel, bone-like apatites doped with Ag+ or co-doped Ag+/peroxide were also prepared for comparative purposes. The compounds were thoroughly characterized by chemical titrations, FTIR, XRD, SEM, and EDX analyses. All doped apatites demonstrated significant antibacterial properties toward four major pathogenic bacteria involved in periodontitis and bone infection, namely Porphyromonas gingivalis (P. gingivalis), Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), Fusobacterium nucleatum (F. nucleatum), and S. aureus. By way of complementary tests to assess protein adsorption, osteoblast cell adhesion, viability and IC50 values, the samples were also shown to be highly biocompatible. In particular, peroxidated apatite was the safest material tested, with the lowest IC50 value toward osteoblast cells. We then demonstrated the possibility to associate such doped apatites with two biocompatible polymers, namely gelatin and poly(lactic-co-glycolic) acid PLGA, to prepare, respectively, composite 2D membranes and 3D scaffolds. The spatial distribution of the apatite particles and polymers was scrutinized by SEM and µCT analyses, and their relevance to the field of bone regeneration was underlined. Such bio-inspired antibacterial apatite compounds, whether pure or associated with (bio)polymers are thus promising candidates in dentistry and orthopedics while providing an alternative to antibiotherapy.
| S-EPMC9503752 | biostudies-literature
Project description:AimsNon-invasive remote patient monitoring is an increasingly popular technique to aid clinicians in the early detection of worsening heart failure (HF) alongside regular follow-ups. However, previous studies have shown mixed results in the performance of such systems. Therefore, we developed and evaluated a personalized monitoring algorithm aimed at increasing positive-predictive-value (PPV) (i.e. alarm quality) and compared performance with simple rule-of-thumb and moving average convergence-divergence algorithms (MACD).Methods and resultsIn this proof-of-concept study, the developed algorithm was applied to retrospective data of daily bodyweight, heart rate, and systolic blood pressure of 74 HF-patients with a median observation period of 327 days (IQR: 183 days), during which 31 patients experienced 64 clinical worsening HF episodes. The algorithm combined information on both the monitored patients and a group of stable HF patients, and is increasingly personalized over time, using linear mixed-effect modelling and statistical process control charts. Optimized on alarm quality, heart rate showed the highest PPV (Personalized: 92%, MACD: 2%, Rule-of-thumb: 7%) with an F1 score of (Personalized: 28%, MACD: 6%, Rule-of-thumb: 8%). Bodyweight demonstrated the lowest PPV (Personalized: 16%, MACD: 0%, Rule-of-thumb: 6%) and F1 score (Personalized: 10%, MACD: 3%, Rule-of-thumb: 7%) overall compared methods.ConclusionThe personalized algorithm with flexible patient-tailored thresholds led to higher PPV, and performance was more sensitive compared to common simple monitoring methods (rule-of-thumb and MACD). However, many episodes of worsening HF remained undetected. Heart rate and systolic blood pressure monitoring outperformed bodyweight in predicting worsening HF. The algorithm source code is publicly available for future validation and improvement.
| S-EPMC10689918 | biostudies-literature
Project description:BackgroundPhysical activity (PA) is important to general health and knee osteoarthritis (OA). Excessive workplace PA is an established risk factor for knee OA however, appropriate methods of measurement are unclear. There is a need to examine and assess the utility of new methods of measuring workplace PA and estimating knee load prior to application to large-scale, knee OA cohorts. Our aims, therefore, were to monitor workplace PA and estimate lower-limb loading across different occupations in health participants.MethodsTwenty-four healthy adults, currently working full-time in a single occupation (≥ 35 h/week) and free of musculoskeletal disease, comorbidity and had no history of lower-limb injury/surgery (past 12-months) were recruited across New South Wales (Australia). A convenience sample was recruited with occupations assigned to levels of workload; sedentary, light manual and heavy manual. Metrics of workplace PA including tasks performed (i.e., sitting), step-count and lower-limb loading were monitored over 10 working days using a daily survey, smartwatch, and a smartphone.ResultsParticipants of light manual occupations had the greatest between-person variations in mean lower-limb load (from 2 to 59 kg*m/s3). Lower-limb load for most participants of the light manual group was similar to a single participant in heavy manual work (30 kg*m/s3) and was at least three times greater than the sedentary group (2 kg*m/s3). The trends of workplace PA over working hours were largely consistent, per individual, but rare events of extreme loads were observed across all participants (up to 760 kg*m/s3).ConclusionsThere are large interpersonal variations in metrics of workplace PA, particularly among light and heavy manual occupations. Our estimates of lower-limb loading were largely consistent with pre-conceived levels of physical demand. We present a new approach to monitoring PA and estimating lower-limb loading, which could be applied to future occupational studies of knee OA.
| S-EPMC8212530 | biostudies-literature