Acta pharmaceutica Sinica. B2026ResearchNon-viral Gene DeliveryDrug Delivery
Li S, Zhang Y, Han Y, Zhao M, Wang Y, Lu J, Et Al.
Neutrophils exhibit significant plasticity within the tumor microenvironment (TME), such as promoting immune suppression, tumor growth, and metastasis. Although various nano drug delivery systems targeting neutrophils have been developed based on their tumor chemotaxis, few studies have focused on designing…
Read the article →Biomaterials 281 (2022ResearchNon-viral Gene Delivery
Azadeh Kheirolomoom, Aris J. Kare, Elizabeth S. Ingham, Ramasamy Paulmurugan, Elise R. Robinson, Mo Baikoghli, Mohammed Inayathullah, Jai W. Seo, James Wang, Brett Z. Fite, Bo Wu, Spencer K. Tumble, Marina N. Raie, R. Holland Cheng, Lisa Nichols, Alexander D. Borowsky, Katherine W. Ferrara
Ex vivo T-cell engineering is effective but complex, costly, and difficult to scale. A method to transfect T cells directly in situ could simplify T-cell immunotherapy, but T-cell targeting may also trigger activation, depletion, cytokine release, and phenotypic changes that must be understood. In vitro: 80% of…
Read the article →Leukemia2021ResearchDrug Delivery
Kinan Alhallak, Jennifer Sun, Katherine Wasden, Nicole Guenthner, Julie O'neal, Barbara Muz, Justin King, Daniel Kohnen, Ravi Vij, Samuel Achilefu, John F. Dipersio, Abdel Kareem Azab
T-cell-based immunotherapies such as CAR-T cells and bispecific T-cell engagers (BiTEs) have shown promise but have significant limitations: (1) poor pharmacokinetics requiring continuous infusion (BiTE half-life ~2 h), and (2) single-antigen targeting leading to antigen-loss tumour escape and relapse. A modular…
Read the article →Drug Delivery and Translational Research2021ResearchDrug Delivery
Yuan Rui, Jordan J. Green
Glioblastoma (GBM) is one of the deadliest primary adult tumours with a median survival of only 14.6 months post-diagnosis, a statistic that has changed little in two decades. While cancer immunotherapy has shown remarkable progress in other solid tumours, the blood-brain barrier (BBB) and the immune-privileged…
Read the article →Nature Communications2021ResearchNon-viral Gene Delivery
Julia Koerner, Dennis Horvath, Valerie L. Herrmann, Anna Mackeracher, Bruno Gander, Hideo Yagita, Jacques Rohayem, Marcus Groettrup
Cancer immunotherapy needs potent, pharmaceutically defined, GMP-compatible adjuvants for clinical translation. Poly(I:C) is a widely used TLR3 agonist but has ill-defined structure, heterogeneity, pyrogen contamination, and toxicity concerns. Riboxxim is a well-defined 100-bp double-stranded RNA with a…
Read the article →ACS Applied Materials & Interfaces2020ResearchNon-viral Gene Delivery
Kwang-Soo Kim, Jun-Hyeok Han, Seung Hee Choi, Hae-Yun Jung, Joo Dong Park, Hee-Jung An, Seong-Eun Kim, Dong-Hyun Kim, Junsang Doh, Dong Keun Han, Ik-Hwan Kim, Wooram Park, Kyung-Soon Park
Natural killer (NK) cells are promising for cancer immunotherapy due to their lower risk of cytokine storm and graft-versus-host disease compared to T cell therapies. However, existing NK cell activation strategies—genetic engineering and cytokine treatment—are inefficient, expensive, and involve complex processing…
Read the article →Molecular Therapy2020ResearchNon-viral Gene Delivery
Xiaojing Shi, Qinqin Cheng, Tianling Hou, Menglu Han, Goar Smbatyan, Julie E. Lang, Alan L. Epstein, Heinz-Josef Lenz, Yong Zhang
Exosomes are nanosized membranous vesicles with unique properties (abundant membrane proteins, high biocompatibility, low immunogenicity) that make them attractive for therapeutic development. While exosomes have been studied as drug delivery vehicles, fewer studies have focused on engineering exosome surface…
Read the article →Journal of Controlled Release2020ResearchNon-viral Gene Delivery
Nour Shobaki, Yusuke Sato, Yuichi Suzuki, Nana Okabe, Hideyoshi Harashima
Tumour-associated macrophages (TAMs) are largely M2-like and promote tumour growth, angiogenesis, metastasis, and immune suppression. There is a need for systemic delivery systems that can target TAMs and manipulate their pro-tumour functions with siRNA for cancer immunotherapy. Optimised CL4H6-LNPs had 90% siRNA…
Read the article →Science Translational Medicine2020ResearchNon-viral Gene Delivery
Xueguang Lu, Lei Miao, Wenting Gao, Ziqi Chen, Kevin J. Mchugh, Yehui Sun, Zachary Tochka, Stephanie Tomasic, Kaitlyn Sadtler, Alain Hyacinthe, Yuxuan Huang, Tyler Graf, Quanyin Hu, Morteza Sarmadi, Robert Langer, Daniel G. Anderson, Ana Jaklenec
STING agonists require frequent intratumoral injections over months to achieve efficacy, leading to poor patient adherence, repeated disruption of the tumour microenvironment, increased metastasis risk, and limited applicability to hard-to-reach tumours. A single-injection delivery system that mimics multiple dosing…
Read the article →PNAS2018ResearchNon-viral Gene Delivery
Colin J. Mckinlay, Nancy L. Benner, Ole A. Haabeth, Robert M. Waymouth, Paul A. Wender
Efficient mRNA delivery to lymphocytes remains a major unmet need for immunotherapy and vaccinology. Current methods rely largely on physical transfection such as electroporation, which is ex vivo, costly, and inefficient; chemical vectors generally achieve low lymphocyte mRNA transfection, especially in vivo. Lead…
Read the article →ACS Applied Bio Materials (Just Accepted Manuscript)2018ResearchNon-viral Gene Delivery
Chao Wang, Pengfei Sun, Gaina Wang, Pengcheng Yuan, Rongcui Jiang, Wenjun Wang, Wei Huang, Quli Fan
Dendritic cell (DC)-based vaccines require efficient antigen delivery, but free ovalbumin (OVA) is poorly taken up by DCs and is often degraded, sequestered, or exocytosed. Existing OVA delivery systems often suffer from low loading capacity (<10%), lack of imaging ability, or chemical modification that can impair…
Read the article →Journal of Visualized Experiments (JoVE)2018ResearchNon-viral Gene Delivery
Elana Ben-Akiva, Kelly R. Rhodes, Randall A. Meyer, Jordan J. Green
Artificial antigen-presenting cells (aAPCs) are promising for immune modulation, and anisotropic (ellipsoidal) particles have shown improved T-cell stimulation over spherical particles. However, widely used methods for generating anisotropic particles, such as thin-film stretching, can be difficult to implement…
Read the article →Nature Communications2017ResearchNon-viral Gene Delivery
Daniela Schmid, Chun Gwon Park, Christina A. Hartl, Nikita Subedi, Adam N. Cartwright, Regina Bou Puerto, Yiran Zheng, James Maiarana, Gordon J. Freeman, Kai W. Wucherpfennig, Darrell J. Irvine, Michael S. Goldberg
Systemic immune stimulation for cancer immunotherapy is associated with autoimmune-type pathologies, as the doses required to break immune tolerance can invoke undesired host-vs.-host effects. Targeting endogenous immune cell subsets in the circulation—which actively migrate into tumours—could concentrate…
Read the article →Biomaterials2017ResearchNon-viral Gene Delivery
Yoshizaki Y, Yuba E, Sakaguchi N, Koiwai K, Harada A, Kono K
Efficient cancer vaccine carriers need both antigen delivery to dendritic cells (DCs) and DC activation. Previous pH-sensitive polymer-modified liposomes delivered antigen to DC cytosol but had limited adjuvant potency, and combining cationic lipid TRX with MPLA reduced antitumor effects, suggesting a need for…
Read the article →Nature Nanotechnology2014ResearchNon-viral Gene Delivery
Tarek R. Fadel, Fiona A. Sharp, Nalini Vudattu, Ragy Ragheb, Justin Garyu, Dongin Kim, Enping Hong, Nan Li, Gary L. Haller, Lisa D. Pfefferle, Sune Justesen, Kevan C. Herold, Tarek M. Fahmy
Adoptive cell transfer of tumour-specific T cells is a promising cancer immunotherapy, but efficient and economical ex vivo expansion of T cells remains a bottleneck. Artificial antigen-presenting cells (aAPCs) with high surface area and modular design could overcome cost and scalability limits of dendritic…
Read the article →Cellular Immunology (Elsevier)2014ResearchNon-viral Gene Delivery
Mingshui Chen, Haichao Ouyang, Shangyong Zhou, Jieyu Li, Yunbin Ye
Agonistic anti-OX40 monoclonal antibody (mAb) can enhance anti-tumour immunity in preclinical models, but as monotherapy it showed only marginal activity and no objective clinical responses in a phase I trial. A delivery system that improves T cell access, multivalent OX40 engagement, and sustained release of…
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