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.
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. -.
Schlich M, Palomba R, Costabile G, Mizrahy S, Pannuzzo M, Peer D, Decuzzi P
Endosomal escape remains the major intracellular barrier for RNA therapeutics. Only a small fraction of RNA delivered by ionizable lipid nanoparticles (LNPs) reaches the cytosol, where siRNA, miRNA, mRNA, and CRISPR components must act. A deeper mechanistic understanding is needed to design next-generation LNPs with improved cytosolic delivery. Only 1–2% of siRNA delivered by MC3-LNPs was visualized in the cytosol in one key study; another estimated ~3.5% cytosolic release. - Endosomal escape occurs in a narrow time window from a hybrid early/late endosome.
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.
Drug penetration into tumors is limited by abnormal vasculature and high interstitial pressure, and chemotherapy causes undesirable adverse effects including bone marrow and gastrointestinal toxicity. Nanotechnology-based drug delivery systems aim to reduce these adverse effects by enhancing penetration and selective drug retention in tumor tissues. A thorough knowledge of the physical properties (size, surface charge, shape, mechanical. 15 nm AuNPs showed highest accumulation in organs (liver, lung, spleen, kidney); only 15 and 50 nm AuNPs crossed the blood-brain barrier. - Renal clearance is rapid for particles <5–6 nm; clearance by liver and spleen.
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;.
Biomaterials and nanoparticles (NPs) used for medical purposes often trigger immune recognition, inflammation, and rapid clearance by the reticuloendothelial system (RES)/mononuclear phagocyte system (MPS). PEGylation and cell-membrane camouflaging are common stealth strategies, but they have limitations, including anti-PEG immune responses. CD47, a “don’t-eat-me” signal, is emerging as an alternative stealth functionalization to improve. CD47-coated polystyrene beads reduced macrophage phagocytosis by 50% compared with CD47-free beads; anti-CD47 antibody abolished the effect. - CD47 immobilization on PVC tubing almost completely inhibited cell.
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.
Dhrisya Chenthamara, Sadhasivam Subramaniam, Sankar Ganesh Ramakrishnan, Swaminathan Krishnaswamy, Musthafa Mohamed Essa, Feng-Huei Lin, And M. Walid Qoronfleh
Despite enormous strides in nanotechnology research and development, it is often confusing for beginners to make an informed choice regarding the nanocarrier system and its potential applications. There is a need to provide a comprehensive overview of commonly used nanomaterials, their core properties, surface functionalization strategies, and the impact of different administration routes on drug delivery efficacy and biological barriers. PEGylated L-asparaginase: Circulation lifetime of 5.7 days in humans compared to 1.2 days for the original enzyme. - Albumin-bound paclitaxel (Abraxane): 4.5-fold increase in paclitaxel transport across endothelial.
Alidha Gafur, Natalia Kristi, Ali Maruf, Guixue Wang, And Zhiyi Ye
Despite decades of nanomedicine development for tumor therapy, less than 1% of systemically administered nanocarriers (NCs) accumulate in solid tumors. This is largely due to protein corona formation during blood circulation, which accelerates clearance and masks targeting ligands. Stealthy (neutral/negatively charged) NCs prolong circulation but hinder cellular uptake, while sticky (positively charged) NCs enhance uptake but are rapidly. Low tumor accumulation baseline: Less than 1% of systemically administered NCs accumulate in solid tumors; nanoparticles of 40–10,000 nm are more prone to liver entrapment (~18–25% ID) than <10 nm particles (~5% ID). -.
PLA and PLGA are FDA-approved, biodegradable polymers widely used for micro- and nanoparticle drug delivery, but their clinical performance depends on biocompatibility, degradation behavior, and drug-release control. This review addresses the need to understand PLA/PLGA tissue responses, degradation pathways, release models, and biomedical applications, especially for vaccines, drugs, and nucleic acids. PLA and PLGA are biocompatible and biodegradable; they hydrolyze to lactic and glycolic acids, enter the Krebs cycle, and are eliminated as CO₂ and water. - Degradation is influenced by molecular weight, crystallinity,.
Polymer–drug conjugates have achieved clinical success, especially PEG–protein conjugates, but translation of many conjugates—particularly polymer–small-molecule anticancer therapeutics—remains limited. This review addresses the need for rational design, better understanding of in vivo barriers, and identification of obstacles to clinical translation. Oncaspar: PEG–L-asparaginase half-life extended to 357 h vs 20 h for unmodified enzyme. - Mircera: PEG–epoetin beta half-life 134 h vs <25 h for other ESAs. - PK1: 15-fold improved plasma half-life and 17–77-fold.
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 ±.
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.
Liposomes are attractive pharmaceutical carriers because they encapsulate hydrophilic and hydrophobic drugs and are biocompatible and biodegradable. However, conventional liposomes suffer from aggregation/fusion, premature payload release, rapid clearance by the mononuclear phagocyte system (MPS), low entrapment efficiency for some drugs, poor target selectivity, and inefficient intracellular delivery. Design optimization is needed to improve. Remote loading achieved encapsulation efficiency up to 90%; cyclodextrin-based loading achieved drug-to-lipid ratios >1000-fold higher than passive loading. - Doxil, a PEGylated liposomal doxorubicin formulation.
Niu Z, Conejos-Sánchez I, Griffin Bt, O’driscoll Cm, Alonso Mj
Peptide and protein therapeutics are highly potent but mostly require parenteral administration because they are degraded in the gastrointestinal tract, poorly permeate the intestinal epithelium, and have low oral bioavailability. Lipid-based nanocarriers are a promising strategy to enable oral peptide delivery by protecting cargo, enhancing permeability, reducing proteolysis, and promoting lymphatic transport. Protein/peptide therapeutic market projected at $180 billion by 2018. - SLNs achieved insulin AE up to 97.8% and DL up to 18.92%; sCT AE ~90%; leuprolide AE ~75%. - Micro/nanoemulsions achieved >80% entrapment for.
Biomaterials must increasingly do more than simply avoid rejection; they must actively mimic biological structures and functions to direct cell behavior, modulate immunity, and repair tissues. This review addresses how biologically inspired polymers can be designed for local tissue engineering, systemic therapeutic functions, and interfacial applications such as adhesives and lubricious coatings. Worm-like polymeric DNA nanoparticles delivered genes to rat liver with expression two and three orders of magnitude higher than rod-like nanoparticles and nanospheres, respectively. - Ellipsoidal aAPCs with high aspect.
Arginine-rich cell-penetrating peptides (CPPs) such as nona-arginine (9R) can effectively translocate covalently attached biomolecules into cells, but poorly deliver electrostatically complexed siRNA, with most CPP:siRNA complexes trapped in endosomes. The mechanism by which ligand attachment to 9R overcomes this barrier to enable functional siRNA delivery was unknown. ### Native 9R vs. Ligand-9R: siRNA Uptake | Formulation | Cell Type | Uptake (MFI, 24 h) | Gene Silencing | |-----------------|---------------|------------------------|-------------------| | 9DR:siRNA | Neuro2a | 6.7 ±.
Li, Y.; Maciel, D.; Rodrigues, J.; Shi, X.; Tomás, H
Despite extensive research, therapeutic delivery still faces major barriers: poor plasma stability, rapid clearance by the reticuloendothelial system (RES), and intracellular obstacles such as endosomal entrapment and lysosomal degradation. Biodegradable polymer nanogels (NGs) — physically or chemically cross-linked, water-swollen, submicrometer hydrophilic polymer networks — are promising because they can encapsulate or conjugate drugs/nucleic. Chitosan/alginate NGs improved gene transfection in 293T cells 4-fold compared with CTS NGs without alginate. - Redox-sensitive HA NGs protected siRNA; 94% remained entrapped after 110 min without GSH, while at 10 mM.
Polymeric gene delivery carriers such as PEI and poly(L-lysine) are heterogeneous and polydisperse, making site-specific multifunctional modification, structure–activity relationship studies, and reproducible clinical manufacturing difficult. This review argues that precisely defined polymeric materials — dendrimers, peptides, and sequence-defined oligoaminoamides — are needed to overcome these limitations. PAMAM dendrimers: Generation 6 (DG6) was an optimal compromise between efficiency and toxicity; partial amide hydrolysis increased transfection activity approximately 100-fold. - Fluorinated PAMAM G5: Low toxicity and.
Therapeutic nucleic acids—including plasmid DNA, mRNA, siRNA, miRNA, antisense oligonucleotides, and aptamers—have broad therapeutic potential, but their delivery to the correct intracellular site of action remains the dominant bottleneck. Polyplexes, formed by electrostatic complexation of nucleic acids with cationic polymers, are a promising non-viral delivery strategy, but their rational design requires a detailed understanding of. First polymer-based human gene therapy study (1994): transferrin-polylysine/IL-2 pDNA polyplexes were used ex vivo to transfect patient melanoma cells as a vaccine. - Clinical scale: by 2012, more than 2000 clinical.
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.
A.L. Silva, R.A. Rosalia, A. Sazak, M.G. Carstens, F. Ossendorp, J. Oostendorp, W. Jiskoot
Overlapping synthetic long peptides (SLPs) are promising for therapeutic cancer vaccination, but Montanide-based formulations have limitations including non-biodegradability, local side effects, poorly controlled release, and limited scalability. PLGA nanoparticles (NPs) offer a biodegradable alternative, but efficient encapsulation of moderately hydrophobic SLPs with low burst release had not been achieved. Standard acidic inner phase: Encapsulation efficiency was very low (1–30%) and burst release was extremely high (>70%) upon resuspension in PBS or IMDM. - Critical role of inner phase pH: Alkaline inner aqueous phase.
