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.
Rasheid Smith, Emad I. Wafa, Sean M. Geary, Kareem Ebeid, Suhaila O. Alhaj-Suliman, Aliasger K. Salem
Cancer vaccines as monotherapies have displayed limited clinical success due to the immunosuppressive tumor microenvironment (TME). Nanoscale formulations can enhance vaccine efficacy by combating TME immunosuppression, but there is a need for novel adjuvant formulations that can be combined with therapeutic cancer vaccines to improve antitumor immune responses and survival. ### Nanoparticle Characterization & Uptake | Parameter | PMG3 | PMG4 | PMG5 | |---------------|----------|----------|----------| | Hydrodynamic diameter | 231.7 ± 2.4 nm | 172.4 ± 3.0 nm | ~170 nm | | Zeta potential |.
Paolo Morfino, Alberto Aimo, Vincenzo Castiglione, Carolina Galvez-Montón, Michele Emdin, Antoni Bayes-Genis
Cardiac fibrosis contributes to the pathogenesis of heart failure, myocardial infarction, and arrhythmias, but no primarily anti-fibrotic drug has been approved for cardiovascular disease. Many candidate anti-fibrotic strategies have shown promise in preclinical models yet failed to demonstrate clear clinical benefit. There is a need to summarize current and emerging therapeutic options and to evaluate a new approach: targeting cardiac. RAAS inhibitors: Lisinopril reduced collagen volume fraction (CVF) vs. hydrochlorothiazide; losartan reduced CVF and PICP; spironolactone/eplerenone reduced PICP/PIIINP and improved diastolic function in some trials. -.
John 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 tumor 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 cells, such as primary T lymphocytes, was unknown. Understanding whether macropinocytosis is required for T cell growth has. ### T Cell Macropinocytosis (Probe Uptake) | Cell Type | Probe | Stimulation | Fold Increase (Stimulated vs. Unstimulated) |.
John Choi, Yuan Rui, Jayoung Kim, Noah Gorelick, David R. Wilson, Kristen Kozielski, Antonella Mangraviti, Eric Sankey, Henry Brem, Betty Tyler, Jordan J. Green, Eric M. Jackson
Medulloblastoma (MB) and atypical teratoid/rhabdoid tumor (AT/RT) are common pediatric brain malignancies. Radiation carries high risks of developmental sequelae in young children, and current treatments remain inadequate. Viral gene therapy has safety concerns in pediatric patients, so a safe, effective nonviral polymeric nanoparticle system is needed for gene delivery to pediatric CNS tumors. Transfection: Several PBAE formulations achieved >50% transfection in both BT-12 and D425 cells with low cytotoxicity. Optimized formulations significantly outperformed 25 kDa PEI and Lipofectamine 3000. - Uptake: 447.
While many reviews have systematically covered different types of formulation materials for gene delivery, a parallel comparison of different formulation materials together with an analysis of the correlation between their material properties and nucleic acid delivery functions has not been conducted. Understanding the property–function correlation of formulation materials is critical for developing applicable vehicles for specific types of. As a review, the key findings are synthesized conclusions from the literature: - Internalization efficiency: Lipofectamine-based lipoplexes achieved ~45% internalization efficiency in A549 cells, compared with ~10% for.
Ewoud B. Compeer, Felix Kraus, Manuela Ecker, Gregory Redpath, Mayan Amiezer, Nils Rother, Philip R. Nicovich, Natasha Kapoor-Kaushik, Qiji Deng, Guerric P.B. Samson, Zhengmin Yang, Jieqiong Lou, Michael Carnell, Haig Vartoukan, Katharina Gaus, Jérémie Rossy
Polarized endocytic recycling of the T cell receptor (TCR) to the immunological synapse is essential for T cell activation, yet the cellular mechanisms that coordinate internalization of surface receptors with sustained delivery back to the plasma membrane remain incompletely understood. The role of flotillins in defining a clathrin-independent endocytic route and supporting receptor recycling is unclear, particularly in the context of TCR. ### TCR Internalization Dynamics | Finding | Detail | |-------------|------------| | TCR internalization | Constitutive in resting cells; rapidly increased upon activation (most molecules internalized within 20 s) | |.
Juan Chen, Xiaobing Yang, Liuqing Huang, Huixian Lai, Chuanhai Gan, Xuetao Luo
Lung cancer has the highest mortality among cancers, and single-agent chemotherapy is often unsuccessful due to drug resistance, insufficient intracellular uptake, nonspecific targeting, and severe systemic toxicity. Combination chemotherapy can suppress drug resistance and achieve synergistic anticancer efficacy, but there is a need for targeted nanocarrier systems that can co-deliver multiple chemotherapeutic agents while providing active. ### Nanoparticle Characterization | Parameter | Result | |---------------|------------| | Hydrodynamic diameter (DLS) | 176 nm | | TEM core diameter | ~80 nm | | Polydispersity index (PDI) | 0.109 ± 0.034 | | Zeta.
Joshua J. Glass, Daniel Yuen, James Rae, Angus P. R. Johnston, Robert G. Parton, Stephen J. Kent, Robert De Rose
Investigations of nanoparticle targeting to immune cells are conventionally restricted to monocultured cell line models that lack the complexity of primary human blood cell populations, including non-specific association with, and competition from, diverse cell types. A more physiologically relevant system using mixed primary human blood cells is needed to evaluate nanoparticle targeting, particularly for therapeutically relevant non-phagocytic. ### Nanoparticle Characterization | Parameter | Untargeted | αCD4 | αCD20 | |---------------|---------------|----------|-----------| | EM diameter (nm) | 42.7 ± 8.3 | 41.3 ± 8.3 | 45.3 ± 6.8 | | DLS hydrodynamic size.
Jing Luo, Caixia Li, Jianlin Chen, Gang Wang, Rong Gao, Zhongwei Gu
Nonviral gene carriers (cationic polymers and lipids) are promising alternatives to viral vectors, but their transfection efficiencies are much lower. While extensive efforts have focused on chemical modification of gene delivery materials, simple optimization of the transfection procedure itself—beyond standard commercial protocols—remains underexplored. A method that can enhance transfection efficiency across multiple cell types without. ### Volume Optimization (PEI, Hep G2, 6-well) | Volume | Transfection Efficiency | vs. Standard | |------------|----------------------------|------------------| | Standard (500 μL complex + 2 mL medium) | Baseline |.
Tim Willinger, Matthew Staron, Shawn M. Ferguson, Pietro De Camilli, Richard A. Flavell
Prolonged T-cell receptor (TCR) signaling is required for T lymphocyte proliferation, yet TCR ligation paradoxically causes internalization and down-modulation of the TCR from the cell surface. It is unknown how TCR signaling is sustained for many hours despite lower surface expression. Understanding whether TCR signaling continues from intracellular compartments after internalization has significant implications for T cell biology and. ### TCR Internalization & Signal Strength | Parameter | Dnm2 HET | Dnm2 KO | Significance | |---------------|--------------|-------------|------------------| | TCR down-modulation (8 h post-stimulation) | ~50% reduction.
Lung cancer chemotherapy is limited by multidrug resistance, severe adverse effects, and poor tumor targeting. A nanocarrier that actively targets lung cancer cells and co-delivers a cytotoxic drug plus therapeutic DNA could improve efficacy and reduce off-target toxicity. Tf₅ₖ-PTX-DNA-NLC: ~133 nm, zeta +19 mV; Tf₁₀ₖ-PTX-DNA-NLC: ~236 nm, zeta +8 mV. - DNA loading ~90–92%; PTX encapsulation ~83–87%. - In vitro IC₅₀: Tf₅ₖ-PTX-DNA-NLC 3.35 µM; Tf₁₀ₖ-PTX-DNA-NLC 7.12 µM; PTX-DNA-NLC 7.36.
Nonviral gene delivery must overcome cellular uptake, endosomal escape, and nuclear transport, but the cellular uptake mechanism of poly(β-amino ester) (PBAE) polyplexes was unknown. Triple-negative breast cancer (TNBC) also lacks effective targeted therapies, making improved nonviral gene delivery strategies desirable. Uptake without inhibitors: 80–90% for all PBAE formulations. B4S4E6 and B4S4E7 gave 88% and 89% uptake and 46% and 52% transfection, respectively. - CvME was the major uptake pathway: genistein reduced uptake by 61%.
Cell-penetrating peptides (CPPs) can internalize 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 mechanism(s) of endosomal escape remain poorly understood. A model system that mimics late endosomal pH gradients is needed to study how. ### pH Gradient Establishment (BR-LUVs) | Vesicle Composition | pH Gradient Efficiency | Comment | |-------------------------|---------------------------|-------------| | POPC/POPG (20% negative) | Strongest | Used for.
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 polymer/DNA ratio 1; LBPAA at 12.5; LPAA at 25. DTT (10 mM) released free pDNA, confirming bioreducible behavior. - Particle size: Only LBPAA condensed pDNA into ~130.
Nonviral gene delivery vectors remain less efficient than viral vectors, and their intracellular fate is strongly influenced by the endocytic route they enter. The cell membrane is now understood to contain lipid raft and non-raft domains, and the initial binding domain can determine the primary endocytic vesicle composition, associated regulators, and downstream trafficking. This review re-examines and reclassifies mammalian endocytic pathways. Reclassification: CME occurs in non-lipid raft domains; phagocytosis and macropinocytosis occur in mixed membrane domains; caveolae-, flotillin-, GRAF1-, Arf6-, and RhoA-dependent pathways occur in lipid raft domains. -.
Extracellular miRNAs are unusually stable in plasma and their circulating levels change with disease, making them promising biomarkers. They are associated with lipid-based carriers—exosomes, microvesicles, apoptotic bodies, and lipoproteins—as well as lipid-free proteins. Whether these carriers mediate functional miRNA transfer between cells and act as a form of intercellular communication was the central gap addressed. Over 1,500 human miRNAs have been curated; each cell type typically contains ~150–300 miRNAs. - HDL was shown to contain miRNAs and deliver them to Huh7 hepatocellular carcinoma cells and SR-BI–overexpressing BHK cells.
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 optimization is still largely trial-and-error. A systematic in vitro study was needed to correlate lipoplex physicochemical properties and intracellular trafficking with transfection efficiency and toxicity. Morphology: Lipofectamine 2000/pDNA lipoplexes formed filaments and granules at weight ratio 3, with diameters from 466 to 1377 nm. DOTAP/pDNA formed more compact globular structures at ratios 6 and 8, with diameters.
Liposomes are versatile, biocompatible vesicular carriers that can encapsulate and deliver DNA or RNA, but the relationship between lipid charge, lipid packing, and gene-delivery efficiency remains complex. This review discusses physical packing parameters and specific lipids used for gene delivery, classified by overall charge. DOTMA facilitated up to 100-fold more efficient gene delivery than DEAE-dextran coprecipitation or calcium phosphate. - DC-Chol produced up to 2–4-fold greater CAT expression and a 4-fold reduction in cytotoxicity.
Schroeder A, Levins Cg, Cortez C, Langer R, Anderson Dg
RNAi has strong therapeutic potential, but clinical translation of siRNA is limited by delivery. siRNA is large, negatively charged, susceptible to nuclease degradation, poorly taken up by cells, and must reach the cytoplasm to engage RISC. Safe and effective lipid-based delivery systems are needed to protect siRNA, promote cellular uptake, enable endosomal escape, and release functional siRNA intracellularly. siRNA duplexes are 21–23 nucleotides, about 7.5 nm long and 2 nm in diameter, with a molecular weight of roughly 13 kDa. - Knockdown duration is often 3–7 days in dividing cells and up to 3–4 weeks in non-dividing.
Gene therapy could induce immunosuppression with greater durability and less toxicity than conventional agents like cyclosporine A, but T cells are notoriously refractory to non-viral gene delivery. An effective, T-cell-targeted, MRI-trackable non-viral vector is needed for immunosuppression in transplantation and autoimmune disease. DNA condensation: Full retardation at N/P ~2.3 for both PEG-g-PEI and PEG-g-PEI-SPION; SPION did not impair condensation. - Cytotoxicity: PEG-modified polyplexes showed much lower cytotoxicity than PEI 25 kDa. At N/P.
Conventional drug delivery faces barriers including rapid clearance, poor intracellular uptake, low target specificity, and toxicity. Nanovehicles (NVs)—nanosized particles capable of entering cells and delivering cargo intracellularly—offer a means to overcome these barriers. The review aims to provide an overview of principles and barriers relevant to intracellular drug and gene transport, accumulation, and retention using NVs, with emphasis. Representative findings from cited literature: - 100 nm PLGA nanoparticles had 2.3-fold greater uptake than 50 nm particles, 1.3-fold vs 500 nm, and 1.8-fold vs 1000 nm in Caco-2 cells. - DOX-dendrimer was >10 times.
Norbert Dinauer, Sabine Balthasar, Carolin Weber, Jörg Kreuter, Klaus Langer, Hagen Von Briesen
Antibody-based therapeutics have shown promise in targeting specific cell types, but their efficacy can be enhanced by conjugation to drug carriers. Nanoparticles as drug carriers offer advantages including high drug loading capacity, controlled release, and protection from degradation. However, achieving selective cellular uptake via receptor-mediated endocytosis requires targeted delivery systems. A nanoparticle platform that can be. ### Nanoparticle Characterization & Antibody Coupling | Parameter | Value | |---------------|-----------| | Nanoparticle size | ~211 nm | | NAv binding capacity | 7.36 × 10⁻¹⁰ mol NAv/mg NPs | | Anti-CD3 binding |.
Mattias Hallbrink, Johannes Oehlke, Gisela Papsdorf, Michael Bienert
Cell-penetrating peptides (CPPs) efficiently translocate across plasma membranes and are promising delivery vectors for therapeutic macromolecules. However, the influence of cell state, density, and peptide-to-cell ratio on CPP uptake and degradation has received little attention. Understanding whether CPP uptake is governed by peptide concentration or by the peptide-to-cell ratio is critical for experimental design and reproducibility, as. ### Effect of Culture Age on MAP Uptake (1 μM, 1 h) | Culture Age | Control Cells (μM) | Energy-Depleted Cells (μM) | |-----------------|-----------------------|-------------------------------| | 2 days | 24 | 20 | | 4.
Young Hun Choi, Feng Liu, Jin-Seok Kim, Young Kweon Choi, Jong Sang Park, Sung Wan Kim
Non-viral gene delivery systems such as poly-L-lysine (PLL) have low immunogenicity compared with viral vectors, but PLL suffers from poor biocompatibility, rapid degradation, and low transfection efficiency. PEGylation was explored to improve solubility, reduce cytotoxicity, and enhance cell permeability for gene delivery. Transfection: PEG-g-PLL showed 5- to 30-fold higher transfection efficiency than PLL alone. Optimal PEG content was 10 mole%; 25 mole% decreased efficiency. - Optimal ratio: Highest transfection at 1:3 DNA:PEG-g-PLL.
