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.
391 articles
S Sarmah, S Baidya, M De
This review surveys lipid nanoparticle composition, ionizable lipid synthesis and strategies to target delivery of fragile RNA therapeutics while addressing tissue selectivity and immune activation.
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 most stable in mouse amniotic fluid; A1 was least stable. A12 had significantly higher bound protein content than A1 (p < 0.0021). - Percent change in PDI inversely correlated with in vitro luciferase.
Read the articleDe R, Mahata Mk, Kim K-T
Drug carriers are as important as drugs themselves, but clinical translation of polymeric nanocarriers (PNCs) remains limited by incomplete understanding of how carrier architecture and physicochemical properties affect loading, circulation, targeting, and release. The review addresses this gap by systematically linking structural varieties of PNCs and their physicochemical properties to drug delivery profiles, and by highlighting. Representative quantitative findings highlighted in the review: - Aspect ratio and uptake: cylindrical particles with aspect ratio 3 were internalized about 4-fold faster than aspect ratio 1 particles in HeLa cells,.
Read the articleFarough Marofi, Roza Motavalli, Vladimir A. Safonov, Lakshmi Thangavelu, Alexei Valerievich Yumashev, Markov Alexander, Navid Shomali, Max Stanley Chartrand, Yashwant Pathak, Mostafa Jarahian, Sepideh Izadi, Ali Hassanzadeh, Naghmeh Shirafkan, Safa Tahmasebi, Farhad Motavalli Khiavi
CAR T cell therapy has transformed treatment of hematologic malignancies, but its efficacy in solid tumors remains unsupported. Solid tumors present distinct barriers—antigen heterogeneity, poor T cell trafficking/infiltration, and an immunosuppressive tumor microenvironment (TME)—that limit CAR T cell function. This review addresses these barriers and evaluates emerging strategies to improve CAR T cell therapy in non-hematologic malignancies. --- - Ovarian cancer: MSLN-CAR NK cells significantly killed MSLN⁺ ovarian cancer cells (SK-OV-3, OVCAR-3) *in vitro*. MUC16-specific CAR T cells eradicated malignant cells in mouse models. TAG72-CAR T and FRα-CAR T inhibited ovarian cancer growth. - Breast cancer: MUC28z CAR T cells (targeting tMUC1) reduced TNBC tumor proliferation and survival in a xenograft model. HRG1β-based CAR T cells inhibited breast cancer via HER family receptors. Anti-HER2 CAR T cells triggered cell death in HER2-overex
Read the articleRobert C. Sterner, Rosalie M. Sterner
CAR-T cell therapy has produced remarkable clinical responses in certain B cell leukemias and lymphomas, but major limitations remain—including life-threatening toxicities, limited efficacy in solid tumors, antigen escape, poor persistence/trafficking, and an immunosuppressive microenvironment. This review addresses these barriers and discusses recent innovations in CAR-T engineering to improve efficacy and safety in both hematological malignancies and solid tumors. --- - Antigen escape: 70–90% of relapsed/refractory ALL patients show durable responses to CD19 CAR-T, but 30–70% of recurrent disease involves CD19 downregulation/loss. BCMA loss also observed in multiple myeloma. - Dual targeting: CD19/CD22 and CD19/BCMA dual-targeted CAR-T cells show promising efficacy and favorable safety in early clinical trials. Tandem HER2/IL13Rα2 CARs improved anti-tumor activity and decreased antigen escape in glioblastoma models. - Toxicity reducti
Read the articleZhaoting 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
Read the articleYingshu Guo, Xiuping Cao, Xiaofei Zheng, Sk Jahir Abbas, Juan Li, Weihong Tan
Cancer treatment still relies heavily on chemotherapy, which causes severe damage to normal cells and systemic side effects. Safer, more selective drug delivery strategies are needed. Nanocarriers based on nucleic acids (NCNAs) are attractive because nucleic acids offer biocompatibility, low toxicity, programmable structures, controllable size, and modifiability—advantages that address limitations of cationic polymers, dendrimers, and inorganic nanoparticles. --- - DNA tetrahedron loaded with 5-fluorouracil: after 12 h co-incubation, the percentage of drug in cells was nearly 40%, demonstrating stable and efficient drug delivery. - DNA/RNA hybrid spherical nucleic acid with siRNA: rapidly absorbed by more than 60 kinds of cells; protected siRNA from enzymatic digestion and released it upon intracellular Dicer cleavage. - Se/Ru metal–organic nanoparticles + siRNA: enhanced cell uptake and promoted siRNA escape from endosomes/lysosomes, p
Read the articleMichael J. Mitchell, Margaret M. Billingsley, Rebecca M. Haley, Marissa E. Wechsler, Nicholas A. Peppas, Robert Langer
Nanoparticle (NP) research has generated promising preclinical results, but clinical translation remains limited. A major barrier is the mismatch between one-size-fits-all NP designs and the heterogeneous biological barriers across patients and diseases. Precision medicine offers patient stratification, but precision therapies still face delivery barriers. This review argues that intelligent NP design can overcome these barriers and improve both general and precision therapeutic outcomes. --- - Tumor accumulation: Meta-analysis of 232 datasets found that, on average, only 0.7% of injected NP doses reach tumors. - EPR effect variability: Up to 10–15% of injected NPs accumulate at tumor sites in some studies, compared with 0.1% of free drug; however, EPR is highly heterogeneous. - Targeted NP limitation: Antibody-targeted NPs interacted with only 2% of tumor cells in one study. - iCluster system: Inhibited tumor growth by up to 95% in viv
Read the articlePaula M. Cevaal, Abdalla Ali, Ewa Czuba-Wojnilowicz, Jori Symons, Sharon R. Lewin, Christina Cortez-Jugo, Frank Caruso
T cells are attractive targets for immunotherapy, cancer, HIV, autoimmunity, and inflammation, but nanoparticle delivery to T cells remains a major technological challenge due to their nonphagocytic nature and multiple physiological barriers. There is a need for rational design principles for in vivo T cell-targeting nanoparticles. --- - Barriers: Only ~2–3% of all T cells are in blood; <5% of administered nanoparticles typically reach target tissue; nanoparticles <~6 nm are renally cleared; T cells are nonphagocytic with low endocytosis rates; slow endosomal acidification in primary T cells can reduce pH-dependent cargo release. - Size rules: For receptor-mediated endocytosis (RME), optimum nanoparticle diameter ~50 nm; <200 nm preferred; >10 nm needed to avoid renal clearance; 10–100 nm ideal for lymph node delivery; <100 nm promotes escape from mononuclear phagocyte system scavenging. - Targeting outcomes: CD3-targeted PBAE/polygluta
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 cells at tumor sites—without systemic exposure—could improve safety and efficacy. ### Thermal Switch Engineering | Parameter | Result | |---------------|------------| | Best HSE repeat number | 7 repeats (5H-7H best; 2H-4H lower response) | | Best core promoter | YB (synthetic) — ~60-fold induction.
Read the articleYuan Rui, Jordan J. Green
Glioblastoma (GBM) is one of the deadliest primary adult tumors 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 tumors, the blood-brain barrier (BBB) and the immune-privileged status of the central nervous system pose unique drug delivery obstacles. A comprehensive understanding of physiological, immunological ### Transport Barriers | **Barrier** | **Key Finding** | |-------------|-----------------| | BBB | Passive transport limited to <400 Da or lipid-soluble molecules; all GBM patients have tumor regions with.
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, >100-fold higher throughput than a single microfluidic channel. - Mixing performance was uniform across 10× and 128× devices; 90% mixing channel length correlated linearly with ln(Pe).
Read the articleMandana T. Manzari, Yosi Shamay, Hiroto Kiguchi, Neal Rosen, Maurizio Scaltriti, And Daniel A. Heller
Precision medicine has transformed cancer therapy by enabling molecular profiling and optimized drug design, but clinical translation of many precision therapeutics is hindered by pharmacological limitations, including toxicities and drug resistance. Drug delivery materials can modulate a drug’s pharmacokinetics, biodistribution, and toxicity without compromising its molecular target engagement, offering a route to improve the therapeutic index. Kinase inhibitor landscape: More than 50 small-molecule protein kinase inhibitors have been FDA-approved, with the majority developed as targeted cancer therapeutics. - Dose-limiting toxicity example: In a phase I trial.
Read the articleMatthew 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 articleSelf-healing polymers can repair damage and recover functionality, potentially extending the lifetime and safety of biomedical devices. Although self-healing hydrogels have been reviewed previously, papers focused specifically on their use in tissue engineering are scarce. This review summarizes fabrication methods, polymers, biomedical examples, and recent progress in self-healing polymers for tissue engineering. Acylhydrazone-crosslinked nanocomposite hydrogel: self-healing efficiency 97.5%; nearly 100% cell viability. - P(BAL-co-DMSA) hydrogel: self-healing within ~5 s in air and underwater; stretchability ~4500%; complete.
Read the articleAnne 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 (
Read the articleAnnika M. Frank, Angela H. Braun, Lea Scheib, Shivani Agarwal, Irene C. Schneider, Floriane Fusil, Severine Perian, Ugur Sahin, Frederic B. Thalheimer, Els Verhoeyen, Christian J. Buchholz
Conventional lentiviral vectors (LVs) are not selective for T cells and cannot efficiently transduce resting or minimally stimulated T lymphocytes, which limits their use for direct in vivo T-cell gene delivery. There is a need for vectors that can both target T cells specifically and activate them sufficiently to permit gene transfer without prior ex vivo activation. --- - Selectivity: CD3-LVs transduced CD3(^+) Jurkat cells but not CD3(^-) Molt4.8 cells. VSV-LV transduced HUVEC (86.74%), HepG2 (32.53%), and Nalm-6 (97.50%) cells, whereas CD3-LVs showed <0.3% transduction in these off-target cells. - Nonactivated T cells: CD3-LVs transduced freshly isolated PBMCs in the absence of cytokines or with IL-2 or IL-7/IL-15 at efficiencies similar to peak activation. VSV-LV was substantially less efficient under these conditions. - Whole blood: CD3-LVs mediated T-cell gene transfer in whole blood without additional stimuli. VCNs: TR66-LV 1.17
Read the articleXiaojing 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 | |.
Julie J.-J. Tang, Alina P. Sung, Mariel J. Guglielmo, Laura N.-G., Doug Redelman, James Smith-Gagen, Diane Hudig
Monoclonal antibody anti-tumor therapies rely on NK cell-mediated antibody-dependent cell-mediated cytotoxicity (ADCC), but patient responses vary widely. While tumor 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 NK cell to kill multiple target cells sequentially—has received little attention. A predictive biomarker for serial ADCC capacity. ### Killing Frequency Variability (E:T=1:4, n=24 donors) | Parameter | All Donors | Females | Males | |---------------|----------------|-------------|-----------| | KF range | 1.1 - 2.2 | 1.1 - 2.2 | 1.2 - 2.1 | | Mean.
Read the articleElana Ben-Akiva, Randall A. Meyer, Hongzhe Yu, Jonathan T. Smith, Drew M. Pardoll, Jordan J. Green
Previous red blood cell (RBC) membrane-coated nanoparticles have all been spherical, missing the physical shape component of biomimicry. Particle shape is a critical design parameter affecting biodistribution, macrophage evasion, and targeted interactions. A platform combining physical biomimicry (anisotropic shape) with chemical biomimicry (RBC membrane coating) could improve circulation time and detoxification efficacy. Macrophage uptake: RBC membrane coating reduced uptake by 30–50%; anisotropic shape reduced uptake by 30–40%; combined coating + anisotropy reduced uptake by 50–70% versus spherical uncoated particles at 4 h. - Blood.
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 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 articleYao Y, Zhou Y, Liu L, Xu Y, Chen Q, Wang Y, Wu S, Deng Y, Zhang J, Shao A.
Conventional chemotherapy and targeted therapy are limited by systemic toxicity, poor tumor targeting, and multidrug resistance (MDR). Nanoparticle-based drug delivery offers improved pharmacokinetics, biocompatibility, enhanced permeability and retention (EPR), precise targeting, and potential to overcome resistance mechanisms such as efflux transporters, defective apoptosis, and hypoxia. NPs with diameters of 10–100 nm are generally suitable for cancer therapy; <10 nm are cleared by kidneys, >100 nm are cleared by phagocytes. - PEGylation reduces opsonization and immune clearance, prolonging.
Read the articleFam Sy, Chee Cf, Yong Cy, Ho Kl, Mariatulqabtiah Ar, Tan Ws.
Nanoparticles (NPs) interact extensively with plasma proteins after intravenous administration and are rapidly cleared by the mononuclear phagocyte system (MPS) or complement system, causing premature drug release at off-target sites. A stealth coating layer can improve blood circulation half-life by escaping immune recognition and clearance. Au-PEG10k: >95% still circulating 1 h after intravenous injection; Au-PEG750 did not show prolonged circulation. - Uncoated Au NPs and Au-PEG750: ~90% captured in liver and spleen after 1 h; Au-PEG10k: <5% at 1 h and.
Read the articleNina 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.
Read the articleWe co-develop nanocarrier and biosensing programs with pharma, biotech and academic groups — from target selection through GMP supply.
