Every entry summarises what the study set out to test, what it found and why it changes how we design delivery systems. Browse research and reviews or search the collection.
586 articles
Showing 1–24 of 87 articles · Keyword: nanocarriers Clear keyword
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Glioblastoma (GBM) remains one of the most aggressive brain malignancies, with limited therapeutic success largely due to the restrictive nature of the Blood-Brain Barrier (BBB) and intrinsic drug resistance mechanisms. Despite standard treatment strategies, the median survival remains approximately 16 months…
Read the articleGrau M, Kostyurina E, Seidl J, Martini N, Winkeljann B, Merkel Om, Et Al.
LAF-Stp xenopeptides (XPs) comprising lipoamino fatty acid (LAF) units connected with the tetraethylene pentamine derived polyamino acid Stp were identified as a novel class of amphiphilic mRNA carriers. A 'chameleon-like' polarity switch is observed upon transition from neutral physiological to endosomal acidic pH…
Read the articleHamideh Parhiz, Jacob S. Brenner, Priyal N. Patel, Tyler E. Papp, Hamna Shahnawaz, Qin Li, Ruiqi Shi, Marco E. Zamora, Amir Yadegari, Oscar A. Marcos-Contreras, Ambika Natesan, Norbert Pardi, Vladimir V. Shuvaev, Raisa Kiseleva, Jacob W. Myerson, Thomas Uhler, Rachel S. Riley, Xuexiang Han, Michael
Nucleoside-modified mRNA lipid nanoparticle (modmRNA-LNP) technology is clinically successful, but its behaviour in pre-existing inflammatory or immune-challenged conditions is poorly characterised. This gap raises the risk of adverse effects when modmRNA-LNPs are administered to patients with ongoing inflammation…
Read the articleKelsey L. Swingle, Margaret M. Billingsley, Sourav K. Bose, Brandon White, Rohan Palanki, Apeksha Dave, Savan K. Patel, Ningqiang Gong, Alex G. Hamilton, Mohamad-Gabriel Alameh, Drew Weissman, William H. Peranteau, Michael J. Mitchell
Congenital protein deficiencies often begin irreversible pathology in utero, but postnatal treatments are limited. In utero mRNA delivery could enable protein replacement before disease onset, yet LNP stability in fetal amniotic fluid and how it affects mRNA delivery had not been previously investigated. LNP A12 was…
Read the articleMartijn J.W. Evers, Wenjuan Du, Qiangbing Yang, Sander A.A. Kooijmans, Aryan Vink, Mies Van Steenbergen, Pieter Vader, Saskia C.A. De Jager, Sabine A. Fuchs, Enrico Mastrobattista, Joost P.G. Sluijter, Zhiyong Lei, Raymond Schiffelers
Modified mRNA (modRNA) is a promising cardiac regeneration therapeutic, but naked mRNA is large, negatively charged, and rapidly degraded. It is unknown whether systemically administered lipid nanoparticles (LNPs) can functionally deliver mRNA to ischaemic/damaged myocardium after myocardial infarction. LNPs were…
Read the articleHanwen Zhang, Xuexiang Han, Mohamad-Gabriel Alameh, Sarah J. Shepherd, Marshall S. Padilla, Lulu Xue, Kamila Butowska, Drew Weissman, Michael J. Mitchell
LNPs can trigger innate immune responses and inflammation, which can suppress mRNA translation and cause adverse effects. There is a need for LNP formulations that reduce LNP-induced inflammation while maintaining or improving mRNA delivery. C9D1 and C10D0 had similar size, PDI, and 90% mRNA encapsulation; Dex…
Read the articleYihua Pei, Yanjie Bao, Cristiano Sacchetti, Juthamart Brady, Kyra Gillard, Hailong Yu, Scott Roberts, Kumar Rajappan, Steven P. Tanis, Carlos G. Perez-Garcia, Padmanabh Chivukula, Priya P. Karmali
Systemic LNP delivery predominantly targets the liver, while extrahepatic delivery—especially to lung airway epithelium for diseases such as cystic fibrosis—remains challenging. DOTAP is a common cationic lipid for lung gene delivery but is racemic, pseudo-glyceryl, and slowly biodegradable. Novel readily…
Read the articleIan C. Miller, Ali Zamat, Lee-Kai Sun, Hathaichanok Phuengkham, Adrian M. Harris, Lena Gamboa, Jason Yang, John P. Murad, Saul J. Priceman, Gabriel A. Kwong
CAR T cell therapy for solid malignancies typically results in poor responses. Systemic administration of immunomodulatory biologics (cytokines, BiTEs) can augment T cell activity but off-target toxicity narrows the therapeutic window. A method to spatially and temporally control transgene expression by engineered T…
Read the articleKinan 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 articleYuan 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 articleSarah J. Shepherd, Claude C. Warzecha, Sagar Yadavali, Rakan El-Mayta, Mohamad-Gabriel Alameh, Lili Wang, Drew Weissman, James M. Wilson, David Issadore, Michael J. Mitchell
Microfluidic mixing can produce precise LNPs but is limited in throughput, while bulk mixing is scalable but yields larger, heterogeneous particles with variable potency. A scalable microfluidic device is needed to produce potent RNA-LNPs across discovery and clinical scales. PMD achieved 18.4 L/h production…
Read the articleJiayu Zhou, Yishu Zhai, Jumei Xu, Tian Zhou, Lian Cen
PLGA microspheres are widely used for controlled drug release, but they often exhibit pronounced initial or mid-term burst release. A strategy is needed to finely tune drug release kinetics and suppress burst release, especially for water-soluble drugs. MSNs: Average size 119 nm; specific surface area 902.53 m²/g…
Read the articleVitor Francisco, Catarina Rebelo, Artur Filipe Rodrigues, Josephine Blersch, Hugo Fernandes, Lino Ferreira
Non-viral vectors such as nanoparticles (NPs) show promise for RNA-based therapies, but suffer from limited cell targeting, poor cellular internalisation, and inadequate endolysosomal escape capacity. The field lacks a systematic, high-throughput approach to identify effective polymeric nanocarriers that can deliver…
Read the articleKelly R. Rhodes, Randall A. Meyer, Justin Wang, Stephany Y. Tzeng, Jordan J. Green
Regulatory T cell (Treg)-based therapeutics show promise for treating autoimmune diseases and preventing transplant rejection, but adoptive Treg transfer is expensive, complex, and difficult to implement. "Off-the-shelf" non-cellular alternatives that can induce endogenous Tregs in vivo are needed. Existing…
Read the articleN.N. Parayath, S.B. Stephan, A.L. Koehne, P.S. Nelson, M.T. Stephan
CAR T and TCR T cell therapies are powerful but face prohibitive costs and manufacturing complexity due to the need for leukapheresis, ex vivo transduction, expansion, and quality control—all under GMP conditions. An "off-the-shelf" injectable nanocarrier that can transiently reprogram circulating T cells in vivo…
Read the articleJohn C. Charpentier, Di Chen, Philip E. Lapinski, Jackson Turner, Irina Grigorova, Joel A. Swanson, Philip D. King
Macropinocytosis has been shown to regulate the growth of Ras-transformed tumour cells under amino acid (AA)-limiting conditions by providing extracellular proteins that are degraded into AA to fuel cell growth and activate mTORC1. However, whether macropinocytosis regulates the growth of non-transformed mammalian…
Read the articleJulie J.-J. Tang, Alina P. Sung, Mariel J. Guglielmo, Laura N.-G., Doug Redelman, James Smith-Gagen, Diane Hudig
Monoclonal antibody anti-tumour therapies rely on NK cell-mediated antibody-dependent cell-mediated cytotoxicity (ADCC), but patient responses vary widely. While tumour antigen escape is one cause of treatment failure, the role of inter-individual variation in NK cell serial killing capacity—the ability of a single…
Read the articleDylan J. Drakes, Sarwish Rafiq, Terence J. Purdon, Andrea V. Lopez, Smita S. Chandran, Christopher A. Klebanoff, Renier J. Brentjens
T-cell receptor (TCR)-modified T-cell gene therapy can target a variety of extracellular and intracellular tumour-associated antigens, yet has had little clinical success. A potential explanation for limited antitumor efficacy is a lack of T-cell activation in vivo, particularly when tumour cells downregulate…
Read the articleBradley Vis, Rachel E. Hewitt, Tom P. Monie, Camilla Fairbairn, Suzanne D. Turner, Stephen D. Kinrade, Jonathan J. Powell
Ultrasmall silica nanoparticles (USSN, <10 nm diameter) were recently shown to stimulate T lymphocytes directly at relatively low exposure doses, but the underlying mechanisms and associated cell signalling were unknown. Understanding whether USSN directly engage the T cell receptor (TCR) complex or act through other…
Read the articleYusuke Sato, Nana Okabe, Yusuke Note, Kazuki Hashiba, Masatoshi Maeki, Manabu Tokeshi, Hideyoshi Harashima
Small-sized lipid nanoparticles (LNPs) are attractive for tissue penetration but often lose potency because lipid components diffuse out and serum proteins adsorb onto poorly packed surfaces. The study asked how the hydrophobic scaffold structure of pH-sensitive cationic lipids affects small-LNP stability, lipid…
Read the articlePedro P. Guimaraes, Rui Zhang, Roman Spektor, Mingchee Tan, Amanda Chung, Margaret M. Billingsley, Rakan El-Mayta, Rachel S. Riley, Lili Wang, James M. Wilson, Michael J. Mitchell
LNP libraries are usually screened in vitro, which poorly predicts in vivo mRNA delivery. A high-throughput in vivo platform was needed to screen many LNP formulations simultaneously and identify lead carriers for functional mRNA delivery. b-mRNA could be detected in liver at doses as low as 17 ng; b-mRNA delivery…
Read the articleDavid N. Nguyen, Theodore L. Roth, P. Jonathan Li, Peixin Amy Chen, Ryan Apathy, Murad R. Mamedov, Linda T. Vo, Victoria R. Tobin, Daniel Goodman, Eric Shifrut, Jeffrey A. Bluestone, Jennifer M. Puck, Francis C. Szoka, Alexander Marson
CRISPR-Cas9 genome editing in clinically relevant primary cells is limited by inefficient homology-directed repair (HDR) and cytotoxicity of exogenous DNA. Improvements are needed to increase editing efficiency, cell viability, and generalizability across cell types for adoptive cell therapies and research. tCTS…
Read the articleCoralie M. Backlund, Christopher R. Hango, Lisa M. Minter, Gregory N. Tew
Intracellular protein and antibody delivery is limited by inefficient carriers, high toxicity, and a frequent requirement for serum-free conditions, especially in difficult-to-transfect cells such as immune cells, stem cells, and neurons. A simple noncovalent carrier that works in complete media and across diverse…
Read the articleLu Sun, Hua Wei, Xiaoshuo Zhang, Chao Meng, Guiying Kang, Wei Ma, Liwei Ma, Baoyan Wang, Cuiyun Yu
Folic acid (FA)-mediated active targeting improves nanocarrier tumour specificity but exposes targeting ligands to the immune system, causing rapid clearance and nonspecific uptake. Existing acid-labile benzoic-imine PEG sheddable systems are insufficiently stable at physiological pH. A more stable, tumour-triggered…
Read the articleWe co-develop nanocarrier and biosensing programmes with pharma, biotech and academic groups — from target selection through scale-up.
