Browsing by Author "Hu, Yun"

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    Development of nanoparticle based nicotine vaccines for smoking cessation
    Hu, Yun (Virginia Tech, 2015-06-15)
    Cigarette smoking is prevalent worldwide and has consistently been the top preventable cause of many serious diseases., which result in huge mortality, morbidity, and economic loss, in recent decades. In recent years, nicotine vaccines that can induce production of nicotine specific antibodies in human have emerged as a promising medicine to treat tobacco addiction. In the past decade, there have been numerous nicotine vaccine candidates evaluated in human clinical trials, including NicVaxNicVAX®, TA-NICTA-NIC®, Nic002NIC002®, NiccineNiccine®, and SEL-068SEL-068®. . However, traditional nicotine vaccine designs haves many disadvantages, including low immunogenicity, low specificity, difficulty in integration of molecular adjuvants, and short immune response persistence. To overcome the above limitations, in this study, various nanoparticle-based vaccine delivery systemsvaccine componentss have been developed and evaluated as potential delivery vehicles for vaccines against nicotine addiction. Firstly, a nicotine vaccine was synthesized by conjugating bovine serum albumin (BSA)-nicotine complex to the surface of nano-sized cationic liposome. Significantly higher anti-nicotine antibody titer was achieved in mice by liposome delivered nicotine vaccine compared with nicotine-BSA vaccine. Secondly, a novel nanoparticle (NP)-based delivery platform was constructed by incorporating a negatively charged nanohorn into cationic liposome to improve the stability of liposome and reduce nanoparticle flocculation. Subsequently, nicotine vaccine was constructed by conjugating nicotine-BSA complex to the surface of the nanohorn supported liposome (NsL). Marked improvement in stability in vitro and significant increase in titer of anti-nicotine antibodies were detected in nanohorn supported liposome ( NsL) delivered vaccine than liposome delivered vaccine. In addition, NsL nicotine vaccine exhibited good safety in mice after multiple injections. Thirdly, lipid- poly(lactic-co-glycolic acid) (PLGA) hybrid NPs were constructed as vaccine delivery system. due to the fact that nanohorn is not currently approved for clinical use, we substituted the nanohorn with poly(lactic-co-glycolic acid) (PLGA) nanoparticles and constructed PLGA-lipid hybrid nanoparticles. Preliminary results showed that PLGA-lipid hybrid NPs nanoparticles exhibited improved stability, better controlled release of antigens, as well as enhanced uptake by dendritic cell (DC). A lipid-PLGA hybrid NPnanoparticle was also developed that was structurally responsive to low pH challenge. The lipid shell of the hybrid nanoparticle was rapidly disintegrated under a low pH challenge, which resembles the acidic environment of endosomes in DCsdendritic cells. The hybrid NPs exhibited minimal antigen release in human serum at physiological pH, but a faster release of antigen from this NP compared to non-pH sensitive NPs was observed in DC. In the final study, hybrid NPnanoparticles with various cholesterol concentrations were constructed. Slower and more controlled release of antigens in both human serum and phosphate buffered saline were detected in nanoparticles with higher cholesterol content. However, nanoparticles containing higher cholesterol showed poorer stability due to increase fusion among NPnanoparticles. It was later found that PEGylation of NPs can effectively minimize fusion caused size increase after long term storage, leading to improved cellular uptake. The findings from this study on the nanohorn-lipids based nicotine vaccine as well as lipid-PLGA hybrid NPs may provide solid basis for future development of lipid-PLGA based nicotine vaccine.
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    In vitro performance of lipid-PLGA hybrid nanoparticles as an antigen delivery system: lipid composition matters
    Hu, Yun; Ehrich, Marion F.; Fuhrman, Kristel; Zhang, Chenming (Springer, 2014-08-27)
    Due to the many beneficial properties combined from both poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and liposomes, lipid-PLGA hybrid NPs have been intensively studied as cancer drug delivery systems, bio-imaging agent carriers, as well as antigen delivery vehicles. However, the impact of lipid composition on the performance of lipid-PLGA hybrid NPs as a delivery system has not been well investigated. In this study, the influence of lipid composition on the stability of the hybrid NPs and in vitro antigen release from NPs under different conditions was examined. The uptake of hybrid NPs with various surface charges by dendritic cells (DCs) was carefully studied. The results showed that PLGA NPs enveloped by a lipid shell with more positive surface charges could improve the stability of the hybrid NPs, enable better controlled release of antigens encapsulated in PLGA NPs, as well as enhance uptake of NPs by DC.
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    The Mobile Base Station Strategy for Wireless Networks With Successive Interference Cancellation
    Shi, Lei; Hu, Yun; Xu, Juan; Shi, Yi; Ding, Xu (IEEE, 2019)
    Successive interference cancellation (SIC) and mobile base stations (MBSs) have been separately exploited to effectively collect data in wireless networks. This paper aims to jointly optimize SIC and MBSs movement to minimize MBS's data collection time for given data. First, we design a DPS algorithm for finding some dominating points (good locations for an MBS) in a two-dimensional area. Based on these dominating points, we build a suitable trajectory for MBS's traveling. Then, we divide the whole traveling path into many path parts and then allocate one or several time slots for each path part. In each time slot, we design a farthest-node-allocation (FNA) algorithm for scheduling node transmissions and determining the MBS's moving speed. The simulation results show that the proposed algorithm can significantly reduce the MBS's data collection time than the scheme without using the SIC.
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    Rationalization of a nanoparticle-based nicotine nanovaccine as an effective next-generation nicotine vaccine: A focus on hapten localization
    Zhao, Zongmin; Hu, Yun; Harmon, Theresa; Pentel, Paul; Ehrich, Marion F.; Zhang, Chenming (2017-09-01)
    A lipid-polymeric hybrid nanoparticle-based next-generation nicotine nanovaccine was rationalized in this study to combat nicotine addiction. A series of nanovaccines, which had nicotine-haptens localized on carrier protein (LPKN), nanoparticle surface (LPNK), or both (LPNKN), were designed to study the impact of hapten localization on their immunological efficacy. All three nanovaccines were efficiently taken up and processed by dendritic cells. LPNKN induced a significantly higher immunogenicity against nicotine and a significantly lower anti-carrier protein antibody level compared to LPKN and LPNK. Meanwhile, it was found that the anti-nicotine antibodies elicited by LPKN and LPNKN bind nicotine stronger than those elicited by LPKN, and LPNK and LPNKN resulted in a more balanced Th1-Th2 immunity than LPKN. Moreover, LPNKN exhibited the best ability to block nicotine from entering the brain of mice. Collectively, the results demonstrated that the immunological efficacy of the hybrid nanoparticle-based nicotine vaccine could be enhanced by modulating hapten localization, providing a promising strategy to combatting nicotine addiction.