Nature Communications2023ResearchNon-viral Gene Delivery
Yue Wang, Shi-Kun Zhou, Yan Wang, Zi-Dong Lu, Yue Zhang, Cong-Fei Xu, Jun Wang
PD-1/PD-L1 blockade therapy is successful but often yields poor benefits due to insufficient T-cell infiltration and low intratumoral concentrations of PD-1/PD-L1 inhibitors. While strategies exist to increase either T-cell recruitment or inhibitor delivery, none actively recruit T cells while achieving tumor-specific delivery of PD-L1 inhibitors to specifically eliminate inhibition of tumor-infiltrating T cells. A strategy that addresses both. ### Nanoparticle Characterization | Parameter | Value | |---------------|-----------| | Hydrodynamic diameter | 107.2 nm | | PDI | ~0.2 | | Zeta potential | +15.3 mV | | Stability in 10% FBS | ≥5 days (size/PDI stable).
Read the article →Advanced Science2023ResearchNon-viral Gene Delivery
Cheng Huang, Xing Duan, Jichao Wang, Qingqing Tian, Yangmei Ren, Kepan Chen, Zongliang Zhang, Yuanyou Li, Yunyu Feng, Kunhong Zhong, Yuelong Wang, Liangxue Zhou, Gang Guo, Xiangrong Song, And Aiping Tong
Bispecific T-cell engagers (BiTEs) are promising but require large amounts of purified protein, have high manufacturing costs, poor in vivo stability, and short serum half-lives. mRNA delivery could enable continuous endogenous production of BiTEs, but efficient and safe delivery systems are needed. The study developed a novel ionizable lipid nanoparticle (LNP) for mRNA encoding B7H3×CD3 BiTE to achieve prolonged half-life and potent antitumor. LNP@GFP-mRNA showed transfection efficiency comparable to Lipofectamine 8000 in 293T, AML12, and LO2 cells; serum presence did not affect transfection. - After IV LNP@Luc-mRNA, strongest luciferase signal was in liver.
Read the article →Bioactive Materials2021ReviewNon-viral Gene Delivery
Muyue Yang, Jipeng Li, Ping Gu, Xianqun Fan
Tumor microenvironment (TME) modulation is a promising strategy in cancer immunotherapy, but conventional immunotherapeutic agents suffer from limited drug retention in the TME, severe adverse events, and low response rates. Nanoparticles can prolong retention, enable targeted delivery to TME components, and convert the immunosuppressive TME into an immunosupportive state, potentially improving therapeutic efficacy while reducing toxicity. DC targeting: CD40-targeted PLGA nanoparticles achieved highest binding/uptake and maximum IL-12 production in vitro; however, T cell proliferation was driven mainly by TLR ligands rather than targeting ligand. -.
Read the article →APL Bioengineering2021ReviewNon-viral Gene Delivery
Matthew R. Aronson, Scott H. Medina, Michael J. Mitchell
Most clinically approved cancer therapies are potent and toxic small molecules limited by severe off-target toxicities and poor tumor-specific localization. Liposomal encapsulation reduces toxicity, but reliance on passive targeting via the enhanced permeability and retention (EPR) effect leaves unresolved issues such as heterogeneous tumor accumulation. Peptide-functionalized liposomes offer an active targeting strategy for receptor-mediated. TfR-targeting T7: D-enantiomer T7 showed increased binding affinity over L-T7 and transferrin; T7-liposomes loaded with docetaxel significantly reduced tumor growth in mice. T7-quercetin liposomes increased cytotoxicity.
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 proteins for cancer immunotherapy. A platform enabling genetic display of bispecific antibodies on exosomes could redirect T cells to. ### SMART-Exo Characterization | Parameter | Result | |---------------|------------| | Size (NTA) | ~109 nm | | Surface scFv per particle | ~1,180 ± 140 molecules | | Yield | 74 μg (5.4 × 10⁹ particles) per 30 mL | |.
Read the article →Cancer Immunology Research (AACR)2020ResearchNon-viral Gene Delivery
Dylan 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 tumor-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 tumor cells downregulate costimulatory molecules. A method to provide a durable proinflammatory signal to TCR-modified T cells could enhance persistence, effector. ### In Vitro T Cell Activation & Cytotoxicity | Parameter | Control | mIL12 pmel-1 | mIL18 pmel-1 | |---------------|-------------|------------------|------------------| | IFNγ secretion | Baseline | Significantly.
Read the article →Polymer Chemistry (Royal Society of Chemistry)2020ResearchDrug Delivery
Lu 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 tumor 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, tumor-triggered sheddable PEG stealth is needed to protect FA in circulation and expose it at tumor sites while also promoting intracellular drug. P1 micelles: \(D_h\) = 41 nm, narrow size distribution; stable at pH 7.4. - pH-triggered destabilization: At pH 6.5, size increased from 41 nm to 80 nm after 24 h; at pH 5.0, size increased to 627 nm. -.
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 tumor microenvironment, increased metastasis risk, and limited applicability to hard-to-reach tumors. A single-injection delivery system that mimics multiple dosing would improve adherence, reduce metastasis risk, and expand clinical utility. Pulsatile release: Microparticles released cargo in pulses at approximately 1, 4, 8, 11, 15, 18, and 97 days in vitro with no detectable leakage before release. In vivo release times for PLGA-1, PLGA-2, and PLGA-3 were.
Read the article →International Immunopharmacology2020ReviewNon-viral Gene Delivery
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.
Read the article →2019ReviewNon-viral Gene Delivery
Jin Q, Deng Y, Chen X, Ji J.
Ideal cancer nanomedicines need a stealth surface for prolonged circulation and tumor accumulation, but stealth surfaces often hinder cellular uptake. Conversely, cationic or targeting-ligand surfaces enhance uptake but cause rapid clearance and off-target interactions. This review addresses the central conflict between stealth and enhanced cellular uptake and summarizes surface-engineering strategies that integrate both properties in one system. Representative quantitative findings from cited studies: - MMP-2-activatable cell-penetrating peptides showed more than 10-fold increased cellular uptake after linker cleavage. - PolyHis-b-PEG micelles: DOX uptake by.
Read the article →Colloids and Surfaces B: Biointerfaces2018ResearchDrug Delivery
Amirhossein Bahreyni, Mona Alibolandi, Mohammad Ramezani, Atefeh Sarafan Sadeghi, Khalil Abnous, Seyed Mohammad Taghdisi
Conventional chemotherapy for breast and colon cancers suffers from low specificity, rapid drug clearance, and severe toxic side effects on healthy tissues, while chemoresistance and metastasis remain major causes of cancer-related mortality. There is an unmet need for targeted delivery systems that can co-deliver chemotherapeutic agents with oligonucleotide-based therapeutics (e.g., miRNA inhibitors) to enhance efficacy and reduce off-target. Epi Release Profile: - ~80% Epi released at pH 5.5 (tumor tissue/lysosomal pH) after 72 h - ~28% Epi released at pH 7.4 (physiological blood pH) after 72 h - Demonstrates pH-responsive release mediated by PβAE.
Read the article →Journal of Controlled Release2016ResearchNon-viral Gene Delivery
Matthias Van Woensel, Nathalie Wauthoz, Rémi Rosière, Véronique Mathieu, Róbert Kiss, Florence Lefranc, Brecht Steelant, Ellen Dilissen, Stefaan W. Van Gool, Thomas Mathivet, Holger Gerhardt, Karim Amighi, Steven De Vleeschouwer
Galectin-1 (Gal-1) is overexpressed in glioblastoma multiforme (GBM), promotes tumor progression, angiogenesis, chemoresistance, and immune suppression. A non-invasive delivery strategy is needed to reach CNS tumors with siRNA while limiting systemic effects. The intranasal route was explored as an underexplored pathway for delivering siRNA-loaded chitosan nanoparticles to GBM. Nanoparticle characteristics: Optimal formulation had Z-average 141 ± 5 nm, PDI 0.3, zeta potential +32 mV, siRNA payload 24 µg/mL, and encapsulation efficiency 81 ± 3%. Freeze-dried particles stored at 4°C remained.
Read the article →2013ResearchNon-viral Gene Delivery
Tzeng, S. Y., Higgins, L. J., Pomper, M. G., & Green, J. J. (2013).
Liver cancer has limited curative options, and transarterial chemoembolization (TACE) provides local access for gene therapy. However, prior nonviral delivery strategies suffered from low in vitro efficacy and high toxicity to healthy liver cells. There is a need for a delivery platform that efficiently transfects hepatoma cells while sparing non-cancer hepatocytes. Hepatoma transfection: 457e, 1.1:1 achieved up to 98 ± 0.4% eGFP transfection in MCA-RH7777 cells with no measurable cytotoxicity. - Hepatocyte transfection/toxicity: BRL-3A transfection reached 73 ± 0.4% with 10 ± 4%.
Read the article →Vaccine2008ResearchNon-viral Gene Delivery
S. Hamdy, O. Molavi, Z. Ma, A. Haddadi, A. Alshamsan, Z. Gobti, S. Elhasi, J. Samuel, A. Lavasanifar
Most PLGA-based cancer vaccine studies used foreign model antigens such as ovalbumin (OVA), which are not subject to central/peripheral tolerance and can overestimate therapeutic efficacy. There is a need to evaluate PLGA vaccines against a realistic, clinically relevant self/tumor antigen (TRP2) and to overcome self-tolerance and the immunosuppressive tumor microenvironment. Co-delivery of a TLR4 ligand (7-acyl lipid A) with a tumor antigen in. Nanoparticle Characterization: - Size 350–410 nm, PDI < 0.2. - TRP2 EE 5.2 ± 0.6%; loading 0.94 ± 0.11 µg/mg. - 7-acyl lipid A EE 67.3 ± 6.9%; loading 1.79 ± 0.18 µg/mg. Normal Mice Vaccination (ELISPOT): - Empty-NP: no.
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