Person: Shi, Jinjun
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Shi
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Jinjun
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Shi, Jinjun
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Publication Efferocytosis drives a tryptophan metabolism pathway in macrophages to promote tissue resolution(Springer Science and Business Media LLC, 2024-09-06) Sukka, Santosh R.; Ampomah, Patrick B.; Darville, Lancia N. F.; Ngai, David; Wang, Xiaobo; Kuriakose, George; Xiao, Yuling; Shi, Jinjun; Koomen, John M.; McCusker, Robert H.; Tabas, IraPublication Nanotechnology in Drug Delivery and Tissue Engineering: From Discovery to Applications(American Chemical Society (ACS), 2010-09-08) Shi, Jinjun; Votruba, Alexander R.; Farokhzad, Omid; Langer, RobertThe application of nanotechnology in medicine, referred to as nanomedicine, is offering numerous exciting possibilities in healthcare. Herein, we discuss two important aspects of nanomedicine—drug delivery and tissue engineering—highlighting the advances we have recently experienced, the challenges we are currently facing, and what we are likely to witness in the near future.Publication Emerging nanotechnology approaches for HIV/AIDS treatment and prevention(Future Medicine Ltd, 2010) Mamo, Tewodros; Moseman, E Ashley; Kolishetti, Nagesh; Salvador-Morales, Carolina; Shi, Jinjun; Kuritzkes, Daniel; Langer, Robert; Andrian, Ulrich von; Farokhzad, OmidCurrently, there is no cure and no preventive vaccine for HIV/AIDS. Combination antiretroviral therapy has dramatically improved treatment, but it has to be taken for a lifetime, has major side effects and is ineffective in patients in whom the virus develops resistance. Nanotechnology is an emerging multidisciplinary field that is revolutionizing medicine in the 21st century. It has a vast potential to radically advance the treatment and prevention of HIV/AIDS. In this review, we discuss the challenges with the current treatment of the disease and shed light on the remarkable potential of nanotechnology to provide more effective treatment and prevention for HIV/AIDS by advancing antiretroviral therapy, gene therapy, immunotherapy, vaccinology and microbicides.Publication Hybrid lipid–polymer nanoparticles for sustained siRNA delivery and gene silencing(Elsevier BV, 2014) Shi, Jinjun; Xu, Yingjie; Xu, Xiaoyang; Zhu, Xi; Pridgen, Eric; Wu, Jun; Votruba, Alexander R.; Swami, Archana; Zetter, Bruce; Farokhzad, OmidThe development of controlled-release nanoparticle (NP) technologies has great potential to further improve the therapeutic efficacy of RNA interference (RNAi), by prolonging the release of small interfering RNA (siRNA) for sustained, long-term gene silencing. Herein, we present a NP platform with sustained siRNA-release properties, which can be self-assembled using biodegradable and biocompatible polymers and lipids. The hybrid lipid-polymer NPs showed excellent silencing efficacy, and the temporal release of siRNA from the NPs continued for over one month. When tested on luciferase-expressed HeLa cells and A549 lung carcinoma cells after short-term transfection, the siRNA NPs showed greater sustained silencing activity than lipofectamine 2000-siRNA complexes. More importantly, the NP-mediated sustained silencing of prohibitin 1 (PHB1) generates more effective tumor cell growth inhibition in vitro and in vivo than the lipofectamine complexes. We expect that this sustained-release siRNA NP platform could be of interest in both fundamental biological studies and clinical applications.Publication Surface De-PEGylation Controls Nanoparticle-Mediated siRNA Delivery In Vitro and In Vivo(Ivyspring International Publisher, 2017) Zhu, Xi; Tao, Wei; Liu, Danny; Wu, Jun; Guo, Zilei; Ji, Xiaoyuan; Bharwani, Zameer; Zhao, Lili; Zhao, Xiaoping; Farokhzad, Omid; Shi, JinjunThe present work proposes a unique de-PEGylation strategy for controllable delivery of small interfering RNA (siRNA) using a robust lipid-polymer hybrid nanoparticle (NP) platform. The self-assembled hybrid NPs are composed of a lipid-poly(ethylene glycol) (lipid-PEG) shell and a polymer/cationic lipid solid core, wherein the lipid-PEG molecules can gradually dissociate from NP surface in the presence of serum albumin. The de-PEGylation kinetics of a series of different lipid-PEGs is measured with their respective NPs, and the NP performance is comprehensively investigated in vitro and in vivo. This systematic study reveals that the lipophilic tails of lipid-PEG dictate its dissociation rate from NP surface, determining the uptake by tumor cells and macrophages, pharmacokinetics, biodistribution, and gene silencing efficacy of these hybrid siRNA NPs. Based on our observations, we here propose that lipid-PEGs with long and saturated lipophilic tails might be required for effective siRNA delivery to tumor cells and gene silencing of the lipid-polymer hybrid NPs after systemic administration.Publication A Solvent-Free Thermosponge Nanoparticle Platform for Efficient Delivery of Labile Proteins(American Chemical Society, 2014) Choi, Won Il; Kamaly, Nazila; Riol-Blanco, Lorena; Lee, In-Hyun; Wu, Jun; Swami, Archana; Vilos, Cristian; Yameen, Basit; Yu, Mikyung; Shi, Jinjun; Tabas, Ira; von Andrian-Werburg, Ulrich; Jon, Sangyong; Farokhzad, OmidProtein therapeutics have gained attention recently for treatment of a myriad of human diseases due to their high potency and unique mechanisms of action. We present the development of a novel polymeric thermosponge nanoparticle for efficient delivery of labile proteins using a solvent-free polymer thermo-expansion mechanism with clinical potential, capable of effectively delivering a range of therapeutic proteins in a sustained manner with no loss of bioactivity, with improved biological half-lives and efficacy in vivo.Publication Adjuvant-carrying synthetic vaccine particles augment the immune response to encapsulated antigen and exhibit strong local immune activation without inducing systemic cytokine release(Elsevier BV, 2014) Ilyinskii, Petr O.; Roy, Christopher J.; O’Neil, Conlin P.; Browning, Erica A.; Pittet, Lynnelle A.; Altreuter, David H.; Alexis, Frank; Tonti, Elena; Shi, Jinjun; Basto, Pamela A.; Iannacone, Matteo; Radovic-Moreno, Aleksandar F.; Langer, Robert; Farokhzad, Omid; von Andrian-Werburg, Ulrich; Johnston, Lloyd P.M.; Kishimoto, Takashi KeiAugmentation of immunogenicity can be achieved by particulate delivery of an antigen and by its co-administration with an adjuvant. However, many adjuvants initiate strong systemic inflammatory reactions in vivo, leading to potential adverse events and safety concerns. We have developed a synthetic vaccine particle (SVP) technology that enables co-encapsulation of antigen with potent adjuvants. We demonstrate that co-delivery of an antigen with a TLR7/8 or TLR9 agonist in synthetic polymer nanoparticles results in a strong augmentation of humoral and cellular immune responses with minimal systemic production of inflammatory cytokines. In contrast, antigen encapsulated into nanoparticles and admixed with free TLR7/8 agonist leads to lower immunogenicity and rapid induction of high levels of inflammatory cytokines in the serum (e.g., TNF-α and IL-6 levels are 50- to 200-fold higher upon injection of free resiquimod (R848) than of nanoparticle-encapsulated R848). Conversely, local immune stimulation as evidenced by cellular infiltration of draining lymph nodes and by intranodal cytokine production was more pronounced and persisted longer when SVP-encapsulated TLR agonists were used. The strong local immune activation achieved using a modular self-assembling nanoparticle platform markedly enhanced immunogenicity and was equally effective whether antigen and adjuvant were co-encapsulated in a single nanoparticle formulation or co-delivered in two separate nanoparticles. Moreover, particle encapsulation enabled the utilization of CpG oligonucleotides with the natural phosphodiester backbone, which are otherwise rapidly hydrolyzed by nucleases in vivo. The use of SVP may enable clinical use of potent TLR agonists as vaccine adjuvants for indications where cellular immunity or robust humoral responses are required.Publication Differentially Charged Hollow Core/Shell Lipid-Polymer-Lipid Hybrid Nanoparticles for Small Interfering RNA Delivery(Wiley-Blackwell, 2011) Shi, Jinjun; Xiao, Zeyu; Votruba, Alexander R.; Vilos, Cristian; Farokhzad, OmidSpeedy delivery: Biodegradable and biocompatible polymers and lipids form hybrid core/shell nanoparticles (see picture, left) that show promising in vitro and in vivo results for delivering siRNA. The unique lipid–polymer–lipid nanostructure is elucidated by electron and fluorescence microscopy (right) and provides the delivery system with distinct functional features.Publication A mucosal vaccine against Chlamydia trachomatis generates two waves of protective memory T cells(American Association for the Advancement of Science (AAAS), 2015) Stary, Georg; Olive, A; Radovic-Moreno, A. F.; Gondek, D.; Alvarez, David; Basto, P. A.; Perro, M.; Vrbanac, Vladimir; Tager, Andrew Martin; Shi, Jinjun; Yethon, J. A.; Farokhzad, Omid; Langer, Robert; Starnbach, Michael; von Andrian-Werburg, UlrichGenital Chlamydia trachomatis (Ct) infection induces protective immunity that depends on interferon-γ producing CD4 T-cells. By contrast, mucosal exposure to ultraviolet light (UV)-inactivated Ct (UV-Ct) generated regulatory T-cells that exacerbated subsequent Ct infection. We show that mucosal immunization with UV-Ct complexed with charge-switching synthetic adjuvant particles (cSAP) elicited long-lived protection in conventional and humanized mice. UV-Ct-cSAP targeted immunogenic uterine CD11b+CD103− dendritic cells (DCs), whereas UV-Ct accumulated in tolerogenic CD11b−CD103+ DCs. Regardless of vaccination route, UV-Ct-cSAP induced systemic memory T-cells, but only mucosal vaccination induced effector T-cells that rapidly seeded uterine mucosa with resident memory T-cells (TRM). Optimal Ct clearance required both TRM seeding and subsequent infection-induced recruitment of circulating memory T-cells. Thus, UV-Ct-cSAP vaccination generated two synergistic memory T-cell subsets with distinct migratory properties.Publication Development of Multinuclear Polymeric Nanoparticles as Robust Protein Nanocarriers(Wiley-Blackwell, 2014) Wu, Jun; Kamaly, Nazila; Shi, Jinjun; Zhao, Lili; Xiao, Zeyu; Hollett, Geoffrey; John, Rohit; Ray, Shaunak; Xu, Xiaoyang; Zhang, Xueqing; Kantoff, Philip; Farokhzad, OmidOne limitation of current biodegradable polymeric nanoparticles is their inability to effectively encapsulate and sustainably release proteins while maintaining protein bioactivity. Here we report the engineering of a PLGA-polycation nanoparticle platform with core-shell structure as a robust vector for the encapsulation and delivery of proteins and peptides. We demonstrate that the optimized nanoparticles can load high amounts of proteins (>20% of nanoparticles by weight) in aqueous solution by simple mixing via electrostatic interactions without organic solvents, forming nanospheres in seconds with diameter <200 nm. We also investigate the relationship between nanosphere size, surface charge, PLGA-polycation composition, and protein loading. The stable nanosphere complexes contain multiple PLGA-polycation nanoparticles, surrounded by large amounts of protein. This study highlights a novel nanoparticle platform and nanotechnology strategy for the delivery of proteins and other relevant molecules.