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.
Hamideh 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 behavior in pre-existing inflammatory or immune-challenged conditions is poorly characterized. This gap raises the risk of adverse effects when modmRNA-LNPs are administered to patients with ongoing inflammation. IE with LPS + modmRNA-LNP: Serum IL-6 increased 14-fold vs LPS alone and 94-fold vs modmRNA-LNP in naive mice. Liver MIP-2 increased 11-fold vs LPS alone and 52-fold vs modmRNA-LNP in naive mice. Liver MIP-2 mRNA.
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. -.
Zhaoting Li, Yixin Wang, Yingyue Ding, Lauren Repp, Glen S. Kwon, Quanyin Hu
Immunotherapy has limited response rates and systemic side effects, and synthetic drug delivery systems can be immunogenic and toxic. Cell-based delivery systems—using endogenous cells as natural carriers—offer low immunogenicity, low toxicity, improved biocompatibility, active tissue targeting, and the ability to cross biological barriers. This review surveys the design principles and immunotherapeutic applications of cell-based delivery systems for cancer, autoimmune diseases, and infectious diseases. --- - RBC hitchhiking: ~11.5% of drug-loaded nanoparticles carrying RBCs targeted the brain, 10× more efficient than traditional brain-targeting carriers. - Platelet-delivered aPDL1 (P-aPDL1): circulating half-life greatly increased vs free aPDL1; effectively prevented tumor recurrence and metastasis after surgery and prolonged survival in mice. - Neutrophil-carried PTX liposomes (PTX-CL/NEs): prolonged survival of glioma-bearing mice ev
Sureshbabu Ram Kumar Pandian, Clayton Fernando Rencllin, Krishnan Sundar
Conventional cancer immunotherapies (checkpoint inhibitors, CAR T cells) are effective but expensive, cause adverse side effects, and face challenges in solid tumours. Nanomaterials offer advantages in delivery, diagnostics, and immune modulation, but a comprehensive understanding of how different nanomaterial types (organic, inorganic, cell membrane-based) can be integrated into cancer immunotherapy—and how their biodistribution and toxicity profiles affect clinical translation—remains needed. --- - Cationic liposomes with α-GalCer and TRP2: Enhanced IFN-γ secretion, cytotoxic T-cell activation, and reduced tumour survival; PEG-coating reduced cytotoxicity. - PLGA nanoparticles with TLR ligands and antigen: Improved antibody and T-cell responses compared to soluble antigen plus adjuvants, resembling live viral vaccine immunogenicity. - Pyruvate dehydrogenase E2 nanoparticles with CpG and gp100: 1.5-fold increase in CD8+ T cells and 5-f
Kinan 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 tumor escape and relapse. A modular nanoparticle platform that addresses both limitations—extending half-life and enabling multispecific targeting—could improve efficacy. ### Nanoparticle Characterization & Pharmacokinetics | Parameter | Result | |---------------|------------| | Liposome size | ~100 nm | | Half-life (non-PEGylated nanoBiTE) | ~36 h | | Half-life (PEGylated nanoBiTE) |.
Gong N, Sheppard Nc, Billingsley Mm, June Ch, Mitchell Mj.
T-cell-based immunotherapies have shown clinical success in B-cell malignancies, but broad implementation is limited by insufficient T-cell expansion, poor trafficking into solid tumours, T-cell exhaustion in hostile tumour microenvironments, and loss of target antigen expression. Nanomaterials may uniquely overcome these barriers through rational design. IL-2-Fc fusion-protein-modified liposomes delivered to the surface of >95% of adoptively transferred T cells, inducing enhanced T-cell proliferation in tumour-bearing mice. - IL-15 superagonist nanogel backpacked onto.
Adoptive T cell therapy has revolutionized treatment of some hematologic malignancies but remains limited in solid tumors—especially central nervous system (CNS) tumors—by poor intratumoral delivery across anatomical barriers, suboptimal T cell specificity or activation, and intratumoral T cell dysfunction caused by immunosuppressive tumor microenvironments. Nanoparticles may overcome these limitations by improving ex vivo T cell manufacture. Representative findings from cited studies: - Nanostructured PEG hydrogels with anti-CD3-conjugated gold nanoparticles enabled T cell activation, proliferation, and memory. - Immunoliposomes targeting CD90 delivered a.
Rumiana Tenchov, Robert E. Bird, Allison E. Curtze, Qiongqiong Angela Zhou
Lipid nanoparticles (LNPs) have become key delivery vehicles across pharmaceuticals, with renewed prominence as the delivery platform for COVID-19 mRNA vaccines. The field lacks a broad, quantitative landscape of LNP research across liposomes, solid lipid nanoparticles, nanostructured lipid carriers, cationic lipid–nucleic acid complexes, and newer architectures. This review provides an overview of LNP structures, properties, applications, and. LNP research is dominated by pharmaceutical applications. The fastest-growing research areas are pharmaceuticals, food and feed, and cosmetics. - The term “liposome” appears in ~147,000 documents from 2000–2020, versus.
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.
Anne Vejux, Dehbia Abed-Vieillard, Khadija Hajji, Amira Zarrouk, John J. Mackrill, Shubhrima Ghosh, Thomas Nury, Aline Yamminse, Mohamed Zaibih, Wafa Mihoubi, Habiba Bouchabi, Boubker Nasser, Yael Grosjean, Gérard Lizard
7-Ketocholesterol (7KC) and 7β-hydroxycholesterol (7β-OHC) are major auto-oxidation products of cholesterol that accumulate in cardiovascular disease, age-related macular degeneration (ARMD), neurodegenerative disorders, and inflammatory bowel diseases. While their cytotoxicity (oxidative stress, organelle dysfunction, cell death, inflammation) is well documented in cell culture, the field lacks a consolidated understanding of how these oxysterols behave in vivo and which model systems (in vitro, animal, and emerging alternatives) are most appropriate for identifying pharmacological targets and protective molecules. This review addresses that gap by systematically surveying the models and mechanisms reported to date. --- 1. Oxiappotophagy is the dominant cell death mode: 7KC and 7β-OHC simultaneously induce oxidative stress (ROS overproduction: O₂⁻, H₂O₂), apoptosis (caspase activation, PARP cleavage, DNA fragmentation), and autophagy (
Melanoma is a poorly immunogenic and highly aggressive skin cancer with limited long-term survival for advanced disease. Dendritic cell (DC)-based vaccines are promising immunotherapies, but their efficacy relies on critical factors including DC maturation state and efficient antigen delivery. Nanoparticulate delivery systems can enhance antigen delivery to ex vivo-generated DCs, mediate DC maturation (adjuvanticity), and promote cytoplasmic antigen presentation through MHC class I—potentially leading to potent antigen-specific immune responses. This review addresses the need to consolidate and evaluate the role of different nanoparticulate delivery systems in ex vivo-generated DC-based vaccines against melanoma. --- - Fusogenic liposomes (FLs): TCL/FLs-pulsed DCs significantly inhibited tumor growth until 17 days post-inoculation; superior to TCL/CLs-pulsed DCs. - Cationic liposomes (Srinivas et al.): Lipid 5 (shikimoyl headgroup) indu
Liu C, Zhang L, Dong N, Zhang W, Chen X, Gao R, Sun H.
Cationic liposomes (CLs) are promising non-viral gene-delivery vectors, but their clinical use in cancer gene therapy is limited by extracellular barriers (opsonization, RES clearance, poor tumor penetration) and intracellular barriers (endosomal/lysosomal entrapment, restricted cytoplasmic/nuclear transport). The review focuses on these barriers and how lipid composition and surface modification can be tailored to improve transfection. CLs face opsonization, RES clearance, poor tumor penetration, endosomal/lysosomal entrapment, and restricted nuclear diffusion. - Protein corona alters CL fate: DOTAP-rich liposomes preferentially bind vitronectin;.
Nina Filipczak, Jiayi Pan, Satya Siva Kishan Yalamarty, Vladimir P. Torchilin
Liposomes remain an important nano-sized drug delivery system because of their biomimetic bilayer, ease of preparation, and biocompatibility, but clinical translation is still limited by reproducibility, scale-up, stability, and payload-specific barriers. The review updates recent advances in liposome preparation, excipients, administration routes, and novel modalities including nucleic acid therapies, CRISPR/Cas9, and immunotherapies. DOTAP-based liposome delivery of Cas9 and sgRNA plasmid achieved 39% gene-editing efficiency in knocking out a GFP reporter in HEK293 cells. - DOTAP/Chol/DOPE liposomes delivering miR-34b-5p to thyroid carcinoma reduced.
Francesca Giulimondi, Luca Digiacomo, Daniela Pozzi, Sara Palchetti, Elisabetta Vulpis, Anna Laura Capriotti, Riccardo Zenezini Chiozzi, Aldo Laganà, Heinz Amenitsch, Laura Masuelli, Giovanna Peruzzi, Morteza Mahmoudi, Isabella Screpanti, Alessandra Zingoni
Liposome clinical translation is limited by opsonization and rapid clearance by immune cells. Although the protein corona is recognized as the liposome’s “biological identity,” it was unclear whether pre-adsorbed corona proteins could help liposomes avoid capture by circulating leukocytes in whole blood and thereby prolong blood residency. Zeta potential: At high HP, zeta potential of DOTAP, DOPC, and DOPG converged to a common negative plateau of ~ −23 mV, independent of pristine surface charge. - Size: DOTAP size increased at low HP, peaked near charge.
Yao Xiao, Kun Shi, Ying Qu, Bingyang Chu, Zhiyong Qian
In the past 10 years, many clinical nano-gene therapy trials have been discontinued due to poor efficacy and serious side effects. There is a critical need to design suitable gene delivery systems that can protect nucleic acids, enhance transfection efficiency, penetrate deep into tumors, and remain stable and safe during blood circulation while accumulating at tumor sites. --- - CALAA-01: Polymer-based NP with transferrin targeting and siRNA against RRM2; dose-dependent tumor accumulation and target inhibition; trial terminated due to 21% adverse event rate from drug instability. - siG12D LODER: PLGA matrix implanted into pancreatic tumors; slow release of siRNA against KRAS G12D; passed phase 1/2a with good anticancer effects. - TKM-080301: SNALP with siRNA against PLK1; evaluated in phase I/II for gastrointestinal neuroendocrine tumors and adrenocortical carcinoma. - PEI-HNPs for CRISPR/Cas9: Achieved up to 60% Cas9 transfection effi
Shaohui Cui, Yueying Wang, Yan Gong, Xiao Lin, Yinan Zhao, Defu Zhi, Quan Zhou, Shubiao Zhang
Cationic lipids are widely used non-viral gene delivery vectors, but their toxicity remains a major bottleneck for clinical translation. Cytotoxicity is strongly associated with the cationic headgroup structure, yet the relationship between headgroup chemistry and toxic mechanisms has been rarely studied. IC50 values: Abstract reports CDA14 = 109.4 µg/mL and CDO14 = 340.5 µg/mL; results section reports CDA14 = 159.4 µg/mL and CDO14 = 340.5 µg/mL. CDO14 was consistently less cytotoxic. - Apoptosis at 120 µg/mL: CDA14.
Tran Th, Tran Ttp, Nguyen Ht, Phung Cd, Jeong J-H, Stenzel Mh, Jin Sg, Yong Cs, Truong Dh, Kim Jo.
Dendritic cell (DC)-based cancer immunotherapy is promising but limited by poor antigen immunogenicity, weak stability, and short in vivo half-life. Nanotechnology can protect antigens and adjuvants from premature degradation, enhance delivery to DCs, and improve therapeutic T cell responses. This review summarizes recent advances in nanoparticle-based systems for DC-targeted cancer immunotherapy. PLGA-conjugated or encapsulated Hp91 peptide activated DCs 5-fold (encapsulated) and 20-fold (surface-conjugated) more potently than free peptide. - Co-delivery of TRP2 and 7-acyl lipid A in PLGA NPs significantly.
Evers Mjw, Kulkarni Ja, Van Der Meel R, Cullis Pr, Vader P, Schiffelers Rm
Free siRNA, mRNA, pDNA, and CRISPR/Cas9 components are rapidly degraded and cleared, so delivery systems are required. LNPs are the most clinically advanced non-viral siRNA carriers; Patisiran reached Phase III and market application in late 2017. The field needed a clearer understanding of LNP design parameters and scalable rapid-mixing production methods. DLin-MC3-DMA has apparent pKa 6.44; LNP formulation at 40/10/40/10 mol% had ED50 0.03 mg/kg, while 50/10/38.5/1.5 mol% had ED50 0.005 mg/kg in mice. - cKK-E12 LNP had ED50 0.002 mg/kg; YSK13-C3 LNP had ED50 0.015 mg/kg.
Cancer stem cells (CSCs) drive tumor heterogeneity, drug resistance, recurrence, and metastasis, limiting conventional chemo/radiotherapy. Liposomal drug delivery systems (LDDSs) are biocompatible, versatile nanocarriers that may overcome CSC-mediated resistance, but their clinical translation remains limited by biological, manufacturing, and targeting barriers. CSCs resist therapy through autophagy, hypoxia/HIF signaling, CSC niche/CAF/MSC support, ECM remodeling, ALDH detoxification, ABC transporter-mediated efflux, enhanced DNA repair, quiescence, activated.
Chao Wang, Wujin Sun, Yanqi Ye, Hunter N. Bomba, Zhen Gu
Immune cell/organ therapies based on manipulation, infusion, and implantation of autologous or allogeneic cells/organs are costly, time-consuming, and sometimes limited in clinical effectiveness. Biomimetic materials and strategies offer an alternative by enabling artificial immune cells and lymphoid organs that are ready-to-use and scalable for immunotherapy. --- - PLGA aAPCs with anti-CD3, anti-CD28, pMHC, and encapsulated IL-2 showed stable ligand presentation for ~20 days, significant IFN-γ secretion, and 45-fold T cell expansion; 6–10 μm particles were most effective. - Ellipsoidal PLGA aAPCs were more efficient than spherical particles; nanoellipsoidal aAPCs stimulated stronger in vivo immune responses at reduced protein dose and showed enhanced pharmacokinetics. - Filamentous anti-CD3 polymers induced more robust T cell responses than PLGA microparticles due to structural flexibility and multivalency. - Magnetic nano-aAPCs with a
Haiqing Bai, Gillian M. Schiralli Lester, Laura C. Petishnok, David A. Dean
Productive gene transfer requires plasmid DNA to not only enter cells but also traffic through the cytoplasm and cross the nuclear envelope. Most transfection strategies focus on membrane entry and promoter choice, but cytoplasmic trafficking and nuclear import are critical, rate-limiting barriers—especially because cytoplasmic nucleases degrade DNA and the nuclear envelope restricts entry in non-dividing cells. --- - Cytoplasmic degradation: Plasmid DNA is degraded in HeLa and COS cell cytoplasm with a half-life of 50–90 min. - Protein–DNA complex: Over 600 proteins associate with the pEGFPN1 plasmid in transfected cells; complexes are dynamic, with some proteins binding for at least 4 h and others associating/disassociating over time. - Diffusion limit: DNA larger than 2000 bp is effectively unable to diffuse through cytoplasm in a physiological time frame due to cytoskeletal networks. - Directed movement: Plasmids containing CREB-bin
Yoshizaki Y, Yuba E, Sakaguchi N, Koiwai K, Harada A, Kono K
Efficient cancer vaccine carriers need both antigen delivery to dendritic cells (DCs) and DC activation. Previous pH-sensitive polymer-modified liposomes delivered antigen to DC cytosol but had limited adjuvant potency, and combining cationic lipid TRX with MPLA reduced antitumor effects, suggesting a need for alternative adjuvant combinations and controlled CpG-DNA delivery to endosomal TLR9. CpG-DNA binding: Pre-mix TRX+ bound >80% of CpG-DNA in feed; Pre-mix TRX− bound <13%. After 24 h, only 3.7 ± 1.3% of CpG-DNA was detected in supernatant, indicating >96% stable binding. - OVA loading: TRX inclusion.
