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.
Sajid Iqbal, Alessandro Francisco Martins, Muhammad Sohail, Jingjing Zhao, Qi Deng, Muhan Li, Zhongxi Zhao
Polymeric gene delivery vectors require detailed physicochemical characterization to ensure reproducible formulation and efficient transfection. PBAE-447 is a promising biodegradable cationic polymer, but its simple nanoparticles can degrade or aggregate in aqueous/physiological conditions. This study characterizes PBAE-447 and evaluates PEGylation and lyophilization to improve stability and transfection. Polymer characterization: Mn 5,354; Mw 9,575; MP 4,934; PDI 1.7. Complete end-capping confirmed by ¹H NMR. - Solubility/buffering/swelling: PBAE-447 completely soluble at 10 µg/µL in NaAc; buffering capacity required.
Mingyuan Li, Yuan Li, Shiqin Li, Lin Jia, Haomeng Wang, Meng Li, Jie Deng, Ali Zhu, Liqiao Ma, Weihong Li, Peng Yu, And Tao Zhu
The COVID-19 pandemic has greatly accelerated the application of mRNA technology, demonstrating its unique advantages over traditional biopharmaceutical and vaccine technology. However, mRNA instability in human physiological environments and inefficient in vivo delivery remain major barriers. mRNA chemical modifications and nano delivery systems are two key factors for in vivo applications. There is a need to summarize challenges for clinical. COVID-19 mRNA vaccine efficacy: BNT162b2 (Pfizer/BioNTech) 95% effective at 30 μg dose; mRNA-1273 (Moderna) 94.5% effective at 100 μg dose; both provide immunogenicity for at least 119 days after first vaccination. -.
Emily Harris, Devon Zimmerman, Eric Warga, Anil Bamezai, Jacob Elmer
Retroviral gene delivery for T cell therapies is expensive, semi-randomly integrating, and variable between patients. Non-viral alternatives are needed, but T cells are notoriously hard to transfect, especially primary T cells. Lipofectamine LTX was the best vehicle in Jurkat cells; optimized conditions in X-VIVO media yielded 63.0 ± 10.9% EGFP+ Jurkat cells vs. 23.1 ± 5.5% in RPMI. - Primary CD3+ T cells reached only 8.1 ± 0.8% EGFP+ under.
siRNA therapeutics are limited by poor cellular uptake, serum nuclease degradation, and inefficient endosomal/lysosomal escape. Chitosan is biocompatible and biodegradable but has low transfection efficiency, largely due to poor buffering capacity and weak endosomal escape. Histidine grafting was explored to add imidazole groups (pKa ~6) that enhance proton-sponge buffering and siRNA delivery. Synthesis: FT-IR showed amide C=O at 1640 cm⁻¹ and N–H bending shift from 1590 to 1522 cm⁻¹; histidine O–H at 3016 cm⁻¹ disappeared. XRD showed loss of histidine crystal peaks at 18.8° and 24.3°, and HGCS polymers were.
Nucleic acid vaccines (DNA and mRNA) offer rapid design, adaptability to changing pathogen strains, and stimulation of both humoral and cellular immunity, but their clinical translation is limited by inefficient delivery—nucleic acids are rapidly degraded by endogenous nucleases, have poor cellular uptake due to their negative charge, and must cross cellular barriers (cytoplasm for mRNA, nucleus for DNA). Nanoparticles (NPs) are promising. mRNA-1273 (Moderna): phase III trial with 30,000+ participants showed 95% efficacy in preventing COVID-19; phase I showed dose-dependent antibody responses (day 57 GMT: 299,751, 782,719, and 1,192,154 for 25, 100, and.
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. A facile, one-step method to activate NK cells without genetic modification or exogenous cytokines is needed. ### Nanoparticle Characterization | Parameter | PDA-NPs | cNPs (PEI-coated) | aNPs (anionic control) | |---------------|-------------|----------------------|---------------------------| | Diameter | 38 nm | 41 nm | Not.
DNA vaccines require high doses because naked DNA is poorly delivered to antigen-presenting cells (APCs), and conventional PLGA microsphere encapsulation by W/O/W emulsion can damage DNA, lower supercoiled DNA content, and give low encapsulation efficiency. A controlled-release system is needed that protects DNA during formulation and enhances immunogenicity at lower doses. Polyplex characterization: PEG-g-PEI/DNA polyplexes at N/P = 20 had a size of 74.1 ± 21.2 nm and zeta potential of 11.47 ± 0.78 mV; transfection peaked at N/P ≥ 20, and cell viability was >90% at N/P ≤ 20. - NIM.
CAR-T cell therapy is limited by complex manufacturing, viral vector use, high cost, and severe toxicities. A nonviral, transient CAR modification approach using self-assembled nanoparticles could provide a simpler, safer, and potentially broadly applicable alternative for T-cell engineering. Formulation screening: pDNA@SNP G1/800 gave the highest luciferase expression in Jurkat cells. Its activity was not significantly different from pDNA@SNP G1/2000 but was higher than other formulations, including up to.
ACS Biomaterials Science & Engineering (as indicated in the supplied file header; exact volume/pages and DOI were not in2020ResearchNon-viral Gene Delivery
Denis Routkevitch, Deepti Sudhakar, Marranne Conge, Mahita Varanasi, Stephany Y. Tzeng, David R. Wilson, Jordan J. Green
The mechanism by which cationic polymers with titratable amines mediate endosomal escape and cytosolic delivery of nucleic acids remains poorly understood. Buffering capacity alone has often failed to predict transfection efficacy, so the study examines whether the effective pKa of poly(beta-amino ester)s (PBAEs) governs cytosolic delivery and transfection. Transfection efficacy: PBAEs achieved up to 99% in HEK293T, 65% in B16-F10, and 90% in GB319 cells, with high viability. - Effective pKa: PBAE 746 = 6.16, PBAE 446 = 6.95, PBAE 447 = 7.15. PEI showed broad buffering.
ACS Biomaterials Science & Engineering (as indicated in the file header; exact volume/pages and DOI were not included in2020ResearchNon-viral Gene Delivery
Denis Routkevitch, Deepti Sudhakar, Marranne Conge, Mahita Varanasi, Stephany Y. Tzeng, David R. Wilson, Jordan J. Green
The mechanism by which cationic polymers with titratable amines mediate endosomal escape and cytosolic delivery of nucleic acids remains poorly understood. Buffering capacity alone has often failed to predict transfection efficacy, so this study examines whether the effective pKa of poly(beta-amino ester)s (PBAEs) governs cytosolic delivery and transfection. Transfection efficacy: PBAEs achieved up to 99% in HEK293T, 65% in B16-F10, and 90% in GB319 cells, with high viability. - Effective pKa: PBAE 746 = 6.16, PBAE 446 = 6.95, PBAE 447 = 7.15. PEI showed broad buffering.
Hashemi V, Farhadi S, Ghasemi Chaleshtari M, Et Al.
Dendritic cell (DC)-based cancer immunotherapy has shown impressive outcomes, including the first FDA-approved anti-cancer vaccine, but clinical application faces challenges such as limited durable responses, antigen selection issues, and immunosuppressive tumor microenvironments. Nanoparticles (NPs) are promising for antigen/adjuvant delivery to DCs and can enhance T cell-stimulating effects while minimizing toxicity. This review surveys cancer. PLGA NPs conjugated/loaded with Hp91 increased DC activation via CD40/CD80 upregulation and IL-6 secretion; in HER2-specific CD8+ T cells, this arrested tumor growth and increased survival. - PLGA NPs loaded with.
Gene therapy is limited by the fragile nature of therapeutic DNA/RNA and by safety concerns with viral vectors. Non-viral polymeric vectors are attractive, but conventional cationic polymers such as PEI, PDMAEMA, and PLL are often non-degradable, causing accumulation, cytotoxicity, and poor gene unpacking. This review addresses the need for biodegradable polymeric vectors that maintain transfection efficiency while improving biocompatibility and. PHP: Degraded to half its original molecular weight in <2 h; complete degradation in about 3 months; transfection efficiency comparable to PLL and not significantly affected by serum proteins. - PAGA: Polyplexes showed.
Wilson, D. R., Rui, Y., Siddiq, K., Routkevitch, D., & Green, J. J. (2019).
Nonviral gene delivery remains limited by low transfection efficacy, especially under physiological serum conditions and at low nanoparticle doses. Although linear poly(β-amino ester)s (PBAEs) are effective, branching structure had not been systematically evaluated in well-defined PBAE-like poly(ester amine) systems. Transfection efficacy: BEAQs achieved up to 99% transfection in HEK293T and 77% in ARPE-19 cells in 10% serum, exceeding linear PBAE and commercial reagents. - High serum: Under 50% serum, B8-50% transfected 98% of.
Yingqi Xu, Dingxin Liu, Jie Hu, Peirong Ding, Meiwan Chen
Triple-negative breast cancer (TNBC) lacks effective targeted therapy. Nonviral co-delivery of an anticancer drug and a therapeutic gene may improve treatment, but efficient tumor-targeted co-delivery remains challenging. TRAIL has shown limited clinical benefit alone, and embelin (EMB) can inhibit XIAP to promote apoptosis. Nanoparticle properties: PPNP CMC = 0.0065 mg/mL. HA coating reduced hemolysis from 37.72% to <0.5%. HA/PPNP remained stable in 10% FBS for 24 h, while PPNP aggregated to ~4000 nm. - Uptake: HA/PPNP increased Nile red.
Endosomal escape remains the rate-limiting step for efficient gene and drug delivery using nanoparticles (NPs). Despite continuous advancements, most NPs internalized via endocytic pathways are degraded by hydrolytic enzymes in lysosomes, severely limiting therapeutic efficacy. There is an unmet need to systematically understand endosomal escape mechanisms and to develop design strategies for endosomolytic agents that can be incorporated into NP. As a review, the key findings are synthesized conclusions from the literature: 1. Endosomal entrapment is a major bottleneck: Most NPs enter cells via endocytic pathways and are degraded in lysosomes; only a small.
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.
Cordeiro, R. A.; Serra, A.; Coelho, J. F. J.; Faneca, H
Gene therapy requires safe and effective delivery vectors. PBAEs are biodegradable cationic polymers with excellent gene delivery properties, but a comprehensive and critical overview of their use as gene carriers is lacking. This review provides the first comprehensive and critical overview of PBAE-based gene delivery systems, from discovery to therapeutic applications, with emphasis on rational design and structure–performance relationships. First library screening (2001): 140 PBAEs from 7 diacrylates and 20 amines; C93 and G28 gave 4–8 times higher transfection than PEI. - Large library (2003): 2,350 structurally unique PBAEs synthesized in a single day;.
Simon A. B. Riedl, Alexander Raup, Patrick Kaiser, Christopher V. Synatschke, Valerie Jérôme, Ruth Freitag
Genetic modification of human T lymphocytes is critical for both basic research and emerging therapies (e.g., CAR-T cells), but established non-viral methods are highly inefficient. Linear polyethylenimine (l-PEI), the "gold standard" for non-viral transfection of mammalian cells, achieves only single-digit percentage transfection rates for T cells. A well-defined polymeric transfection agent that can efficiently and safely transfect T. ### Polyplex Characterization | Parameter | PDMAEMA Nanostar Polyplexes | |---------------|----------------------------------| | Size (N/P 20, in HBG) | 70.4 ± 4.5 nm (stable over time) | | Zeta potential (N/P 3) |.
David P. Walsh, Robert D. Murphy, Angela Panarella, Rosanne M. Raftery, Brenton Cavanagh, Jeremy C. Simpson, Fergal J. O’brien, Andreas Heise, Sally-Ann Cryan
Tissue engineering needs efficient, biocompatible non-viral gene delivery to mesenchymal stem cells (MSCs), which are inherently refractory to transfection. Existing vectors have limitations: PEI is cytotoxic and linear poly(L-lysine) (L-PLL) has poor transfection efficiency. Transfection efficiency (pGFP, day 7): 64-star-PLL = 24.6 ± 0.7%; 32-star-PLL = 22.3 ± 15.1%; 16-star-PLL = 2.0 ± 0.2%; L-PLL = 2.5 ± 0.5%. - Luciferase expression: 64-star-PLL-pGLuc (1 µg, N/P 5) reached 5.5 × 10⁶ ±.
Susanne Przybylski, Michaela Gasch, Anne Marschner, Marcus Ebert, Alexander Ewe, Gisa Helmig, Nadja Hilger, Stephan Fricke, Susanne Rudzok, Achim Aigner, Jana Burkhardt
Nanoparticle-based gene delivery methods are promising for transfecting immune cells, but their impact on basic immune functions such as proliferation—a cornerstone of cellular immunity—has not been systematically investigated. Understanding whether transfection reagents non-specifically influence immune cell proliferation is critical for both therapeutic applications (where effects may be beneficial or detrimental) and for accurately. ### Proliferation Effects (PBMCs, AON/siRNA Transfection) | Reagent | Magnetic Enhancement | Proliferation Change (vs. Control) | Significance |.
Camila G. Zamboni, Kristen L. Kozielski, Hannah J. Vaughan, Maisa M. Nakata, Jayoung Kim, Luke J. Higgins, Martin G. Pomper, Jordan J. Green
Hepatocellular carcinoma (HCC) has poor survival and standard therapies are limited by off-target toxicity to healthy hepatocytes and drug resistance. Gene therapy is promising, but non-viral vectors often suffer from poor intracellular delivery and lack of cancer specificity. A biodegradable polymeric nanoparticle system is needed to deliver DNA preferentially to HCC cells while sparing healthy liver cells. Lead formulation: 536 at 25 w/w was the only PBAE that effectively transfected all nine HCC lines while maintaining THLE-3 viability >80%. - Transfection efficacy: eGFP expression ranged from 36.9% ± 0.4 to 83.5% ± 0.5.
Clinical translation of biomaterial-based gene delivery nanoparticles is limited by efficacy, safety, batch-to-batch consistency, scalable manufacturing, and long-term storage stability. Continuous microfluidic fabrication may overcome manufacturing and scale-up challenges for biodegradable PBAE/DNA polyplexes. DNA integrity: No plasmid DNA shearing up to 240 mL/h; PBAE 446 bound 100% of DNA at 10, 30, 60, and 90 w/w. - Nanoparticle properties: DNA-containing nanoparticle size distribution remained approximately constant.
Jiménez Blanco Jl, Benito Jm, Ortiz Mellet C, García Fernández Jm.
Nonviral gene delivery lacks molecularly well-defined carriers suitable for rigorous structure–activity relationship (SAR) studies. Viral vectors raise immunogenicity, cost, and cargo-size concerns, while polymers, dendrimers, and cationic lipids are often polydisperse or supramolecularly ill-defined. The review argues that “molecular nanoparticles” (MNPs)—monodisperse, shape-persistent molecular entities—can provide programmable, single-isomer. Optimized polycationic amphiphilic cyclodextrins (e.g., 5 and 6) formed 80–100 nm CDplexes at N/P >2 and mediated transfection comparable to or better than PEI/Lipofectamine LTX in COS-7, HeLa, HepG2, and BNL-CL2 cells.
