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 →RSC Advances2019ReviewDrug Delivery
Sima Rezvantalab And Mostafa Keshavarz Moraveji
PLGA is a biocompatible, biodegradable copolymer widely used in drug delivery systems (DDS), but conventional bulk synthesis methods suffer from poor control over particle size, broad size distribution, low drug loading/encapsulation efficiency, and burst release. Microfluidic systems offer a tightly controlled…
Read the article →Nature Reviews Chemistry2018ReviewNon-viral Gene Delivery
Irene Lostalé-Seijo And Javier Montenegro
Gene therapy has enormous therapeutic potential, but clinical translation is limited by the delivery problem: nucleic acids are negatively charged, unstable, and must overcome multiple biological barriers to reach their intracellular site of action. Viral vectors are efficient but suffer from immunogenicity, limited…
Read the article →Annual Review of Chemical and Biomolecular Engineering2018ReviewNon-viral Gene Delivery
Karlsson, J.; Vaughan, H. J.; Green, J. J
Biodegradable polymeric nanoparticles have great potential to improve cancer therapy by enabling targeted delivery, triggered release, and reduced off-target toxicity. This review addresses how such nanocarriers can be engineered to overcome systemic, organ-level, and cellular barriers and to target cancer cells…
Read the article →Current Opinion in Biomedical Engineering2018ReviewNon-viral Gene Delivery
Tzeng Sy, Green Jj
Nucleic acids can be used to engineer the immune system, but their clinical use requires better specificity and intracellular delivery efficiency. Viral vectors have manufacturing, cargo-capacity, safety, and immunological drawbacks; therefore, polymers are being developed as non-viral delivery vehicles whose…
Read the article →Chemical Society Reviews2017ReviewNon-viral Gene Delivery
Shahed Behzadi, Vahid Serpooshan, Wei Tao, Majd A. Hamaly, Mahmoud Y. Alkawareek, Erik C. Dreaden, Dennis Brown, Alaaldin M. Alkilany, Omid C. Farokhzad, Morteza Mahmoudi
Nanoparticles (NPs) are increasingly used in consumer goods, electronics, and pharmaceuticals, but their beneficial and/or deleterious effects ultimately arise from interactions at the cellular and subcellular level. While many NPs require safe entry into cells for therapeutic efficacy, efficient and controlled…
Read the article →Nature Reviews Materials2017ReviewNon-viral Gene Delivery
Khalid A. Hajj And Kathryn A. Whitehead
mRNA therapeutics have enormous potential for vaccines, cancer immunotherapy, protein replacement, and gene editing, but widespread clinical application is limited by the lack of safe and effective delivery vehicles. Naked mRNA is large (~10⁵–10⁶ Da), densely negatively charged, and rapidly degraded by nucleases; its…
Read the article →Frontiers in Immunology.2017ReviewDrug Delivery
Mizrahy S, Hazan-Halevy I, Landesman-Milo D, Ng Bd, Peer D
Current cancer immunotherapy shows promise but fails across many tumour types, likely because single-pathway treatments cannot overcome the complex immunosuppressive tumour microenvironment (TME). Lipid-based nanoparticles (LNPs) may allow simultaneous, temporally coordinated delivery of multiple immune modulators to…
Read the article →Journal of Controlled Release.2017ReviewNon-viral Gene Delivery
Tapeinos C, Battaglini M, Ciofani G
Delivery of therapeutics to the CNS is severely limited by the blood–brain barrier (BBB). Polymeric and inorganic nanoparticles have shown utility but face toxicity, scalability, and organic-solvent concerns. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are biocompatible lipid-based…
Read the article →International Journal of Pharmaceutics.2017ReviewNon-viral Gene Delivery
RNA interference (RNAi) therapeutics have shown potential for treating genetic, viral, and cancerous diseases, but the main bottleneck remains delivery of functional RNA molecules into the cell cytoplasm. The review focuses on liposomes and other lipid carriers, and on exosomes/extracellular vesicles (EVs), as…
Read the article →WIREs Nanomedicine and Nanobiotechnology2017ReviewNon-viral Gene Delivery
Selby, L. I.; Cortez-Jugo, C. M.; Such, G. K.; Johnston, A. P. R
Endosomal escape is widely considered the rate-limiting bottleneck for cytoplasmic delivery of nucleic acids, proteins, and other therapeutics using polymeric and lipid nanoparticles. The field lacks robust methods to quantify escape efficiency and understand its mechanisms, limiting rational design of improved…
Read the article →Materials2017ReviewNon-viral Gene Delivery
Sun, X.; Wu, G.; Xu, C.; Ye, Q.; Wang, C
Periodontitis causes irreversible destruction of periodontal tissues, and regeneration requires biomaterials with suitable mechanical, degradation, and biological properties. PLGA is attractive for periodontal regeneration because of its biocompatibility, tunable degradation, and processability, but its…
Read the article →Molecular Therapy — Methods & Clinical Development2016ReviewNon-viral Gene Delivery
Chen J, Guo Z, Tian H, Chen X.
Gene therapy is a promising strategy for treating gene-associated diseases, but clinical application is limited by inefficient delivery. Naked nucleic acids suffer from nuclease degradation, rapid renal clearance, phagocyte uptake, poor target-cell uptake, and immune-related toxicity. Nanoparticles are considered the…
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 →2016ReviewDrug Delivery
Rizwanullah M, Ahmad J, Amin S
Conventional cancer chemotherapy suffers from poor drug specificity, narrow therapeutic windows, high dose-limiting toxicity, and multidrug resistance (MDR). Nanostructured lipid carriers (NLCs) are biocompatible, biodegradable lipid-based nanoparticles that can improve solubility, stability, targeting, and…
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 →Advanced Drug Delivery Reviews2016ReviewNon-viral Gene Delivery
Suk, J. S.; Xu, Q.; Kim, N.; Hanes, J.; Ensign, L. M
PEGylation is widely used to improve nanoparticle drug and gene delivery by reducing aggregation, opsonisation, and phagocytic clearance, thereby prolonging circulation. However, the field lacks a consolidated understanding of how PEG molecular weight, surface density, conformation, core properties, administration…
Read the article →2015ReviewNon-viral Gene Delivery
Xue Hy, Guo P, Wen W-C, Wong Hl
RNAi therapeutics such as siRNA and miRNA can potently and specifically silence almost any gene, but systemic delivery is limited by poor cell permeation, rapid nuclease degradation, immunogenicity, and lack of target specificity. Lipid-based nanocarriers are among the most biocompatible and clinically advanced…
Read the article →Journal of Controlled Release2015ReviewDrug Delivery
Helin Xu, Qing Yao, Cuifang Cai, Jinxin Gou, Yu Zhang, Haijun Zhong, Xing Tang
Amphiphilic poly(amino acid)-based micelles are attractive for systemic drug delivery because they are biodegradable, biocompatible, have functional side groups, can load diverse drugs, and can exploit the EPR effect. However, low cargo capacity and poor stability in blood remain major barriers to clinical…
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 →Journal of Controlled Release2015ReviewNon-viral Gene Delivery
Bishop, C. J.; Kozielski, K. L.; Green, J. J
Viral vectors raise safety concerns, and non-viral polymeric vectors still require optimisation for clinical translation. This review addresses how polymer structural features govern intracellular nucleic acid delivery — including cargo protection, cellular uptake, endosomal escape, unpacking, and nuclear delivery —…
Read the article →2015ReviewNon-viral Gene Delivery
Li, L.; Wei, Y.; Gong, C
Viral vectors are efficient but carry risks of immunogenicity, inflammatory reactions, recombination, limited DNA cargo capacity, and manufacturing difficulties. Non-viral polymeric vectors are safer and easier to produce, but their transfection efficiency remains much lower than viral vectors because of multiple…
Read the article →Journal of drug targeting2015ReviewNon-viral Gene Delivery
Kim J, Wilson Dr, Zamboni Cg, Green Jj
Cancer gene therapy requires safe and efficient delivery of nucleic acids, but viral vectors carry risks of immunogenicity and insertional tumorigenicity, while non-viral polymeric vectors are safer but less efficient. The review addresses the need for targeted polymeric nanoparticles that achieve tumour-specific…
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