International Journal of Nanomedicine2015ResearchDrug Delivery
Chun-Ying Qu, Min Zhou, Ying-Wei Chen, Mei-Mei Chen, Feng Shen, Lei-Ming Xu
5-Fluorouracil (5-FU) plus cisplatin (CDDP) is a first-line gastric cancer chemotherapy regimen, but it causes substantial toxicity and 5-FU has poor biopharmaceutical properties. A targeted nanoparticle platform could codeliver both drugs, improve synergy, and reduce systemic toxicity. Optimal HA coating…
Read the article →Polymers for Advanced Technologies (Polym. Adv. Technol.)2014ResearchNon-viral Gene Delivery
Hongsuk Park, Joseph W. Nichols, Han Chang Kang, You Han Bae
Bioreducible polymers are attractive as gene carriers because they can reduce cytotoxicity compared with non-degradable cationic polymers such as polyethyleneimine (PEI). However, the safety and transfection efficiency of spermine-based bioreducible polyspermines had not been directly compared with linear PEI (lPEI)…
Read the article →BMC Immunology2014ResearchNon-viral Gene Delivery
Kyung Hee Noh, Yeong Min Park, Hyuk Soon Kim, Tae Heung Kang, Kwon‐ho Song, Young‐ho Lee, Yeongseon Byeon, Hat Nim Jeon, In Duk Jung, Byung Cheol Shin, Kyung‐mi Lee, Seung‐yong Seong, Hee Dong Han, Tae Woo Kim
Conventional adjuvants such as Complete Freund’s Adjuvant (CFA) and Incomplete Freund’s Adjuvant (IFA) are potent but toxic, limiting clinical use. A safer, biodegradable adjuvant system was needed to enhance antigen-specific humoral and cellular immunity without severe local or systemic side effects. Safety: CH-HG…
Read the article →Bioconjugate Chemistry2014ResearchNon-viral Gene Delivery
Hauptmann N, Pion M, Wehner R, Muñoz-Fernández M-A, Schmitz M, Voit B, Appelhans D
Dendritic cell (DC)-based immunotherapy requires efficient delivery of antigens to immature DCs (iDCs) and maintenance of their immunostimulatory and migratory functions. Cationic PEI carriers are limited by dose-dependent toxicity and aggregation at endosomal pH, so a biocompatible, pH-responsive carrier is needed…
Read the article →Pharmaceutical Development and Technology (Informa Healthcare)2014ResearchNon-viral Gene Delivery
Jaber Emami, Aida Pourmashhadi, Hojat Sadeghi, Jaleh Varshosaz, Hamed Hamishehkar
COX-2 is overexpressed in non-small cell lung cancer (NSCLC) and is associated with poor prognosis. Celecoxib (Cxb), a COX-2 inhibitor, has antiproliferative and proapoptotic effects, but systemic administration carries cardiovascular risks. Pulmonary inhalation delivery of Cxb encapsulated in biodegradable PLGA…
Read the article →PLOS ONE2013ResearchNon-viral Gene Delivery
Lais Chayabam, Aline Laino Sodre, Bruno A. Curzio, Martin H. Bonamino
Genetic modification of T lymphocytes is essential for both basic research and immunotherapy (e.g., CAR-T cell generation), but existing methods rely on expensive commercial electroporation kits (Lonza Nucleofector® kits) or time-consuming viral vector production. The high cost and dependence on proprietary reagents…
Read the article →Biochimica et Biophysica Acta (BBA) - Biomembranes2013ResearchNon-viral Gene Delivery
Fatemeh Madani, Rania Abdo, Staffan Lindberg, Hisaaki Hirose, Shiroh Futaki, Ulo Langel, Astrid Gräslund
Cell-penetrating peptides (CPPs) can internalise cells with biologically active cargo, but endosomal entrapment is a major limitation for cytoplasmic delivery, as cargo molecules must escape the endosome before degradation and acidification. While CPPs are known to enter cells via endocytosis, the background…
Read the article →The Journal of Immunology2013ResearchNon-viral Gene Delivery
Ying-Chun Lo, Michael A. Edidin, Jonathan D. Powell
Soluble anti-CD3 antibodies are potent T cell mitogens but activate all T cells regardless of TCR specificity, limiting their therapeutic utility for boosting antigen-specific responses. TCRs cluster into microclusters on the surface of antigen-experienced T cells but remain dispersed on naive T cells. This…
Read the article →ACS Applied Materials & Interfaces (Just Accepted Manuscript)2013ResearchNon-viral Gene Delivery
Cuicui Li, Stephany Y. Tzeng, Liane E. Tellier, Jordan J. Green
DNA-based therapeutics require an intracellular delivery system to be effective. For diseases like brain cancer—where local access to residual tumour is often available following surgical resection—an implantable device that enables both controlled release and intracellular delivery of DNA could open new…
Read the article →Biotechnology and Bioengineering, Vol. 110, No. 3, March2013ResearchNon-viral Gene Delivery
Branching architecture is a tunable parameter for polymeric gene carriers, but how the degree of branching (DB) of bioreducible poly(amido amine)s (PAAs) affects pDNA binding, cellular uptake, endocytosis pathways, and transfection efficiency was not well defined. pDNA condensation: HBPAA completely retarded pDNA at…
Read the article →J. Phys. Chem. B2013ResearchNon-viral Gene Delivery
Tiia-Maaria Ketola, Martina Hanzlíková, Linda Leppänen, Manuela Raviña, Corey J. Bishop, Jordan J. Green, Arto O. Urtti, Helge J. Lemmetyinen, Marjo L. Yliperttula, Elina Vuorimaa
The structure–activity relationships governing polyplex formation by PEI and PLL are not well understood, especially whether DNA binding is independent or cooperative and how pH affects the mechanism. This limits rational design of nonviral gene delivery vectors. Polyplex core formation was complete at approximately…
Read the article →PNAS2012ResearchNon-viral Gene Delivery
David N. Nguyen, Kerry P. Mahon, Ghania Chikh, Phillip Kim, Hattie Chung, Alain P. Vicari, Kevin T. Love, Michael Goldberg, Steve Chen, Arthur M. Krieg, Jianzhu Chen, Robert Langer, Daniel G. Anderson
TLR7/8 agonists are promising vaccine adjuvants and antivirals, but RNA agonists are unstable and small-molecule agonists cause systemic toxicity. A delivery system specifically designed to deliver immunostimulatory RNA (isRNA) to TLR-expressing cells could enable safer and more localised innate immune activation. 14…
Read the article →Journal of Controlled Release2012ResearchNon-viral Gene Delivery
Hughes Ad, King Mr
Metastasis is the leading cause of cancer mortality, and circulating tumour cells (CTCs) are key to metastatic spread. Doxorubicin (DXR) is effective but systemically toxic and nonspecific. A targeted delivery system was needed to capture and kill CTCs under physiologically relevant flow while reducing off-target…
Read the article →Journal of Controlled Release2012ResearchNon-viral Gene Delivery
Nianxi Zhao, Jianjun Qi, Zihua Zeng, Parag Parekh, Chung-Che Chang, Ching-Hsuan Tung, Youli Zu
Suspension lymphoma/leukemia cells are notoriously hard to transfect with non-viral vectors. Existing methods such as Lipofectamine give poor plasmid DNA delivery in these cells, and viral methods raise safety concerns. A simple, efficient, biodegradable cationic polymer nanocomplex is needed for gene delivery to…
Read the article →African Journal of Biotechnology2011ResearchNon-viral Gene Delivery
Wang B, Zhou J, Cui S, Yang B, Zhao Y, Zhao B, Duan Y, Zhang S
Although cationic liposomes are widely used non-viral gene vectors, the structure–activity relationships governing their transfection efficiency remain poorly understood, and optimisation is still largely trial-and-error. A systematic in vitro study was needed to correlate lipoplex physicochemical properties and…
Read the article →Journal of Controlled Release2011ResearchNon-viral Gene Delivery
Tae-Il Kim, Thomas Rothmund, Thomas Kissel, Sung Wan Kim
Endosomal escape remains a major barrier for polymeric gene delivery. Arginine-grafted bioreducible polymers (ABPs) show high transfection via cell-penetrating arginine, but the effect of adding endosome-buffering moieties on their biophysical and transfection properties was not well defined. Buffering capacity…
Read the article →Biomacromolecules2011ResearchNon-viral Gene Delivery
Joel C. Sunshine, Marib I. Akanda, David Li, Kristen L. Kozielski, Jordan J. Green
Non-viral gene delivery needs safer and more effective polymeric vectors. Poly(β-amino ester)s (PBAEs) are promising, but previous studies had not systematically modified all three structural elements—backbone, side chain, and end group—within one library to analyse how small structural changes affect transfection…
Read the article →Proceedings of the National Academy of Sciences of the United States of America (PNAS)2011ResearchDrug Delivery
Che-Ming J. Hu, Li Zhang, Santosh Aryal, Connie Cheung, Ronnie H. Fang, Liangfang Zhang
Long-circulating nanoparticles are needed for sustained systemic drug delivery, but PEGylation—the current stealth gold standard—can face anti-PEG immune responses. A top-down biomimetic approach using natural erythrocyte membranes could better mimic red blood cells (RBCs), nature’s long-circulating carriers, while…
Read the article →Nanomedicine: Nanotechnology, Biology, and Medicine2011ResearchNon-viral Gene Delivery
Shashi Prasad, Virginia Cody, Jennifer K. Saucier-Sawyer, W. Mark Saltzman, Clarence T. Sasaki, Richard L. Edelson, Martin A. Birchall, Douglas J. Hanlon
Efficient antigen delivery remains a major challenge for dendritic cell (DC)-based immunotherapy of solid-organ malignancies. Soluble tumour lysates suffer from instability, poor DC internalisation, and inefficient cross-presentation to cytotoxic T lymphocytes. PLGA nanoparticles may protect antigens, improve…
Read the article →Biomaterials2011ResearchNon-viral Gene Delivery
Dai J, Zou S, Pei Y, Cheng D, Ai H, Shuai X
PEI is an effective gene carrier but high-molecular-weight PEI is nonbiodegradable and cytotoxic; PLL is biodegradable but lacks proton-buffering capacity, has low transfection efficiency, and is also cytotoxic. A vector combining the complementary strengths of PEI and PLL is needed. Cytotoxicity: At 100 µg/mL, PPL…
Read the article →Journal of Controlled Release2011ResearchNon-viral Gene Delivery
Yanan Yue, Fan Jin, Rui Deng, Jinge Cai, Zhuojun Dai, Marie C.M. Lin, Hsiang‐fu Kung, Maria Ahlm Mattebjerg, Thomas Lars Andresen, Chi Chung Wu
PEI is one of the best nonviral gene delivery vectors, but why it works so well remains unclear. In particular, the role of free, uncomplexed PEI chains and their length in transfection, cellular uptake, and endosomal escape has not been quantitatively resolved, and the “proton sponge” mechanism is increasingly…
Read the article →Biomaterials2011ResearchNon-viral Gene Delivery
Stephany Y. Tzeng, Hugo Guerrero‐cazares, Elliott E. Martinez, Joel C. Sunshine, Alfredo Quiñones‐hinojosa, Jordan J. Green
Glioblastoma (GB) has poor survival and current therapies are insufficient. Viral gene therapy carries safety risks, while nonviral vectors often lack efficiency and practical storage stability. PBAEs had shown high transfection and low toxicity in other cell types but had not been tested in primary brain tumour…
Read the article →Acta Pharmacologica Sinica2010ResearchNon-viral Gene Delivery
Jian Li, Ying-Zi He, Wen Li, Yun-Zhen Shen, Yu-Ru Li, Yun-Feng Wang
Non-viral gene delivery systems offer advantages in safety and ease of preparation over viral vectors, but suffer from limited transfection efficiency. While polymer-lipid hybrid nanoparticles (PLN) have shown promise as non-viral vectors, the incorporation of PEGylated lipids to enhance circulation time and…
Read the article →2010ResearchNon-viral Gene Delivery
Kai K. Ewert, Alexandra Zidovska, Ayesha Ahmad, Nathan F. Bouxsein, Heather M. Evans, Christopher S. Mcallister, Charles E. Samuel, Cyrus R. Safinya
Cationic lipid–nucleic acid (CL-NA) complexes are promising non-viral vectors for gene delivery and siRNA-mediated silencing, but their transfection and silencing efficiencies remain low compared with viral vectors. A major gap is poor mechanistic understanding of how complex structure, membrane charge density, and…
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