Nanoparticles with High Drug Loading and Circulation Stability for Systemic Delivery of Anticancer Drugs

Nanoparticles have been pursued as a promising strategy to improve the safety and therapeutic efficacy of systemic chemotherapy, but clinical translation of nanoparticle drug carriers has been slow. Several reasons account for the tedious progress. From the formulation perspective, drug loading efficiency and circulation stability remain to be improved: Low drug loading increases the amount of co-delivered carrier materials, imposing biological burdens to patients. Poor circulation stability compromises the pharmacokinetic benefits of nanoparticles. To develop nanoparticles with high drug loading efficiency and circulation stability, albumin-coated nanocrystal (“Abxtal”) formulation of hydrophobic anti-cancer drugs was developed. Abxtal consists of drug nanocrystals and albumin coating, where albumin serves as a stealth coating to reduce protein adsorption and a mediator of cellular uptake by cancer cells. When Abxtal formulation for paclitaxel was compared with Abraxane®, an FDA-approved albumin-paclitaxel nanoparticle formulation, Abxtal showed superior anti-tumor efficacy at the equivalent dose in a mouse model of B16F10 melanoma. A comparative pharmacokinetics/biodistribution (PK/BD) study confirmed that the superior performance of Abxtal was due to its prolonged circulation in blood and greater tumor accumulation relative to Abraxane. Protein binding to surface of nanoparticles is another important factor that determines the biological fate of the nanoparticles. When the effect of surface chemistry on the formation of protein corona was studied, albumin coating provided protective effects against opsonization, consistent with the known role of albumin as a dysopsonin. The early difference in serum protein binding led to differential macrophage uptake of nanocrystal, contributing to the superior in vivo performance of Abxtal. Overall, the improved therapeutic efficacy of Abxtal is attributable to its higher circulation stability and dysopsonin function of albumin, resulting in preferential tumor accumulation. Furthermore, the broad utility of Abxtal formulation as an enabling formulation for hydrophobic small molecule drugs was demonstrated with docetaxel and carfilzomib. Abxtal formulation of docetaxel entered drug-resistant NCI/ADR-RES ovarian cancer cells by interactions with albumin-receptors, showing the potential utility in the treatment of multidrug-resistant tumors. Abxtal formulation of carfilzomib protected the drug from enzymatic degradation, leading to enhanced bioavailability relative to the solvent- or cyclodextrin-solubilized formulations. In tandem with the robust nanoparticle platform development, the utility of nanoparticles in immune checkpoint blockade therapy has been explored. Specifically, it is envisioned that nanoparticle delivery of the chemotherapeutic that functions as immunogenic cell death inducer will synergize with immune checkpoint blockade. The underlying hypothesis is that nanoparticles will help immune checkpoint blockade therapy by (i) improving the delivery of immunogenic cell death inducers; (ii) altering the cellular uptake mechanism and intracellular stress; (iii) creating, binding and retaining neo-antigens in situ and delivering them to antigen presenting cells; and (iv) co-delivering immune adjuvants. Preliminary studies were performed to determine their ability to induce immunogenic cell death. The release of damage-associated molecular patterns from B16F10 melanoma cells treated with different nanoparticle formulations was examined as in vitro measures of immunogenic cell death induction

An algorithm for 3D shape matching using spherical sectioning

Abstract: 3D shape searching is a problem of current interest in several different fields. Most techniques are developed for a particular domain and used to reduce a shape into a simpler shape representation. The techniques developed for a particular domain will also find application in other domains. We propose a new shape matching method. The SSRD (spherical sectioning railroad diagram) algorithm has the general shape distribution's properties and overall features of the original model. The SSRD's useful properties are discussed. We show the experimental results for the validity of our method

Clinical effectiveness of the sequential 4-channel NMES compared with that of the conventional 2-channel NMES for the treatment of dysphagia in a prospective double-blind randomized controlled study

Background To date, conventional swallowing therapies and 2-channel neuromuscular electrical stimulation (NMES) are standard treatments for dysphagia. The precise mechanism of 2-channel NMES treatment has not been determined, and there are controversies regarding the efficacy of this therapy. The sequential 4-channel NMES was recently developed and its action is based on the normal contractile sequence of swallowing-related muscles. Objective To evaluate and compare the rehabilitative effectiveness of the sequential 4-channel NMES with that of conventional 2-channel NMES. Methods In this prospective randomized case–control study, 26 subjects with dysphagia were enrolled. All participants received 2- or 4-channel NMES for 2–3weeks (minimal session: 7 times, treatment duration: 300–800min). Twelve subjects in the 4-channel NMES group and eleven subjects in the 2-channel NMES group completed the intervention. Initial and follow-up evaluations were performed using the videofluoroscopic dysphagia scale (VDS), the penetration-aspiration scale (PAS), the MD Anderson dysphagia inventory (MDADI), the functional oral intake scale (FOIS), and the Likert scale. Results The sequential 4-channel NMES group experienced significant improvement in their VDS (oral, pharyngeal, and total), PAS, FOIS, and MDADI (emotional, functional, and physical subsets) scores, based on their pretreatment data. VDS (oral, pharyngeal, and total) and MDADI (emotional and physical subsets) scores, but not PAS and FOIS scores, significantly improved in the 2-channel NMES group posttreatment. When the two groups were directly compared, the 4-channel NMES group showed significant improvement in oral and total VDS scores. Conclusions The sequential 4-channel NMES, through its activation of the suprahyoid and thyrohyoid muscles, and other infrahyoid muscles mimicking physiological activation, may be a new effective treatment for dysphagia. Trial registration: clinicaltrial.gov, registration number: NCT03670498, registered 13 September 2018, https://clinicaltrials.gov/ct2/show/NCT03670498?term=NCT03670498&draw=2&rank=1 .This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant Number: HI18C1169). This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Min‑ istry of Science, ICT and Future Planning (NRF- NRF-2016R1D1A1B03935130)

Contributions to OH reactivity from unexplored volatile organic compounds measured by PTR-ToF-MS - A case study in a suburban forest of the Seoul metropolitan area during the Korea-United States Air Quality Study (KORUS-AQ) 2016

We report OH reactivity observations by a chemical ionization mass spectrometer–comparative reactivity method (CIMS-CRM) instrument in a suburban forest of the Seoul metropolitan area (SMA) during the Korea–United States Air Quality Study (KORUS-AQ 2016) from mid-May to mid-June of 2016. A comprehensive observational suite was deployed to quantify reactive trace gases inside of the forest canopy including a high-resolution proton transfer reaction time-of-flight mass spectrometer (PTR-ToF-MS). An average OH reactivity of 30:75:1 s1 was observed, while the OH reactivity calculated from CO, NOCNO2 (NOx ), ozone (O3), sulfur dioxide (SO2), and 14 volatile organic compounds (VOCs) was 11:81:0 s1. An analysis of 346 peaks from the PTR-ToF-MS accounted for an additional 6:02:2 s1 of the total measured OH reactivity, leaving 42.0% missing OH reactivity. A series of analyses indicate that the missing OH reactivity most likely comes from VOC oxidation products of both biogenic and anthropogenic origin.This research has been supported by NASA (grant no. NNX15AT90G), the National Institute of Environmental Research (NIER-RP0219-152) of South Korea, and the Brain Pool Program of the National Research Foundation Korea (NRF) funded by the Ministry of Science and ICT (no. 2020H1D3A2A01060699).Peer reviewe

OH reactivity in urban and suburban regions in Seoul, South Korea – an East Asian megacity in a rapid transition

South Korea has recently achieved developed country status with the second largest megacity in the world, the Seoul Metropolitan Area (SMA). This study provides insights into future changes in air quality for rapidly emerging megacities in the East Asian region. We present total OH reactivity observations in the SMA conducted at an urban Seoul site (May-June, 2015) and a suburban forest site (Sep, 2015). The total OH reactivity in an urban site during the daytime was observed at similar levels (∼15 s(-1)) to those previously reported from other East Asian megacity studies. Trace gas observations indicate that OH reactivity is largely accounted for by NOX (∼50%) followed by volatile organic compounds (VOCs) (∼35%). Isoprene accounts for a substantial fraction of OH reactivity among the comprehensive VOC observational dataset (25-47%). In general, observed total OH reactivity can be accounted for by the observed trace gas dataset. However, observed total OH reactivity in the suburban forest area cannot be largely accounted for (∼70%) by the trace gas measurements. The importance of biogenic VOC (BVOCs) emissions and oxidations used to evaluate the impacts of East Asian megacity outflows for the regional air quality and climate contexts are highlighted in this study

Development of Engine Clutch Control for Parallel Hybrid Vehicles

The parallel hybrid configuration in which a clutch is installed between an engine and a motor can shift its operation mode between pure electric and hybrid vehicle mode by engaging or disengaging the clutch. To enhance drivability of the system in shifting its operation mode, it is required to prepare appropriate measures to control the clutch in response to driving conditions. This paper introduces the hydraulic clutch control strategy which is composed of a synchronized engaging and a launch slip engaging maneuver. The strategy also covers the criteria to decide the proper engaging method between above two candidates for current circumstance. This study also deals with the learning algorithm to compensate the variations of the clutch hardware and to realize consistent drivability across all units. The learning algorithm utilizes the traction motor and a pressure sensor to identify the all the variation terms of the clutch with the required level of accurac

A Systematic Survey on Android API Usage for Data-Driven Analytics with Smartphones

Recent industrial and academic research has focused on data-driven analytics with smartphones by collecting user interaction, context, and device systems data through Application Programming interfaces (APIs) and sensors. The Android OS provides various APIs to collect such mobile usage and sensor data for third-party developers. Usage Statistics API (US API) and Accessibility Service API (AS API) are representative Android APIs for collecting app usage data and are used for various research purposes as they can collect fine-grained interaction data (e.g., app usage history, user interaction type). Furthermore, other sensor APIs help to collect a user's context and device state data, along with AS/US APIs. This review investigates mobile usage and sensor data-driven research using AS/US APIs, by categorizing the research purposes and the data types. In this paper, the surveyed studies are classified as follows: five themes and 21 subthemes, and a four-layer hierarchical data classification structure. This allows us to identify a data usage trend and derive insight into data collection according to research purposes. Several limitations and future research directions of mobile usage and sensor data-driven analytics research are discussed, including the impact of changes in the Android API versions on research, the privacy and data quality issues, and the mitigation of reproducibility risks with standardized data typology.Comment: This paper has been accepted by ACM Computing Surveys (CSUR), 202

Secure Three-Factor Authentication Protocol for Multi-Gateway IoT Environments

Internet of Things (IoT) environments such as smart homes, smart factories, and smart buildings have become a part of our lives. The services of IoT environments are provided through wireless networks to legal users. However, the wireless network is an open channel, which is insecure to attacks from adversaries such as replay attacks, impersonation attacks, and invasions of privacy. To provide secure IoT services to users, mutual authentication protocols have attracted much attention as consequential security issues, and numerous protocols have been studied. In 2017, Bae et al. presented a smartcard-based two-factor authentication protocol for multi-gateway IoT environments. However, we point out that Bae et al.’s protocol is vulnerable to user impersonation attacks, gateway spoofing attacks, and session key disclosure, and cannot provide a mutual authentication. In addition, we propose a three-factor mutual authentication protocol for multi-gateway IoT environments to resolve these security weaknesses. Then, we use Burrows–Abadi–Needham (BAN) logic to prove that the proposed protocol achieves secure mutual authentication, and we use the Automated Validation of Internet Security Protocols and Applications (AVISPA) tool to analyze a formal security verification. In conclusion, our proposed protocol is secure and applicable in multi-gateway IoT environments