European Journal of Medicinal Chemistry2022ReviewNon-viral Gene Delivery
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…
Read the article →Bioengineering & Translational Medicine2021ReviewNon-viral Gene Delivery
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 ionisable 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…
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 tumour-specific localisation. Liposomal encapsulation reduces toxicity, but reliance on passive targeting via the enhanced permeability and retention (EPR) effect leaves unresolved issues…
Read the article →Journal of Oncology2020ReviewDrug Delivery
Zein R, Sharrouf W, Selting K.
Drug penetration into tumours 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…
Read the article →2020ReviewNon-viral Gene Delivery
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 (opsonisation, RES clearance, poor tumour penetration) and intracellular barriers (endosomal/lysosomal entrapment, restricted cytoplasmic/nuclear transport). The…
Read the article →2019ReviewNon-viral Gene Delivery
Gheibi Hayat Sm, Bianconi V, Pirro M, Sahebkar A.
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…
Read the article →Biochimie2019ReviewDrug Delivery
Aqeel Ahmad, Javed Masood Khan, Shafiul Haque
Endosomal escape remains the rate-limiting step for efficient gene and drug delivery using nanoparticles (NPs). Despite continuous advancements, most NPs internalised via endocytic pathways are degraded by hydrolytic enzymes in lysosomes, severely limiting therapeutic efficacy. There is an unmet need to…
Read the article →Pharmaceutics (MDPI)2019ReviewNon-viral Gene Delivery
Run Ni, Ruoyu Fang, And Ying Chau
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…
Read the article →Biomaterials Research2019ReviewDrug Delivery
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…
Read the article →Biomaterials Science2019ReviewNon-viral Gene Delivery
Alidha Gafur, Natalia Kristi, Ali Maruf, Guixue Wang, And Zhiyi Ye
Despite decades of nanomedicine development for tumour therapy, less than 1% of systemically administered nanocarriers (NCs) accumulate in solid tumours. This is largely due to protein corona formation during blood circulation, which accelerates clearance and masks targeting ligands. Stealthy (neutral/negatively…
Read the article →Journal of Pharmaceutical Investigation2019ReviewDrug Delivery
PLA and PLGA are FDA-approved, biodegradable polymers widely used for micro- and nanoparticle drug delivery, but their clinical performance depends on biocompatibility, degradation behaviour, and drug-release control. This review addresses the need to understand PLA/PLGA tissue responses, degradation pathways…
Read the article →Nature Reviews Drug Discovery2019ReviewNon-viral Gene Delivery
Ekliadious, I.; Colson, Y. L.; Grinstaff, M. W
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…
Read the article →Pharmaceutical Research2018ResearchNon-viral Gene Delivery
Francesca Sacchetti, Gaetano Marverti, Domenico D’arca, Leda Severi, Eleonora Maretti, Valentina Iannuccelli, Salvatore Pacifico, Glauco Ponterini, Maria Paola Costi, Eliana Leo
PEGylated pH-sensitive liposomes may improve delivery of anti-cancer peptides, but PEGylation can reduce cellular uptake and endosomal escape (“PEG dilemma”), and it was unknown whether PEGylated liposome components interfere with the intracellular mechanism of action of the delivered drug. Physicochemical…
Read the article →Molecular Pharmaceutics (Just Accepted Manuscript)2018ResearchNon-viral Gene Delivery
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)…
Read the article →International Journal of Pharmaceutics2018ReviewNon-viral Gene Delivery
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 summarises…
Read the article →2017ReviewNon-viral Gene Delivery
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…
Read the article →Advanced Drug Delivery Reviews2016ReviewDrug Delivery
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…
Read the article →Nature2016ReviewNon-viral Gene Delivery
Green, J. J.; Elisseeff, J. H
Biomaterials must increasingly do more than simply avoid rejection; they must actively mimic biological structures and functions to direct cell behaviour, modulate immunity, and repair tissues. This review addresses how biologically inspired polymers can be designed for local tissue engineering, systemic therapeutic…
Read the article →Cell Chemical Biology (Chemistry & Biology)2015ResearchNon-viral Gene Delivery
Skye Zeller, Chang Seon Choi, Pradeep D. Uchil, Hong-Seok Ban, Alyssa Siefert, Tarek M. Fahmy, Walther Mothes, Sang-Kyung Lee, Priti Kumar
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…
Read the article →Chemical Reviews2015ReviewNon-viral Gene Delivery
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…
Read the article →Macromolecular Bioscience2015ReviewNon-viral Gene Delivery
He, D.; Wagner, E
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…
Read the article →Chemical Reviews2015ReviewNon-viral Gene Delivery
Ulrich Lächelt And Ernst Wagner
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…
Read the article →Biochimica et Biophysica Acta (BBA) - Biomembranes2013ResearchNon-viral Gene Delivery
Fatemeh Madani, Rania Abdo, Staffan Lindberg, Hisaaki Hirose, Shiroh Futaki, Ulo Langel, Astrid Gräslund
Cell-penetrating peptides (CPPs) can internalise 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…
Read the article →European Journal of Pharmaceutics and Biopharmaceutics2013ResearchNon-viral Gene Delivery
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…
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