Nature Reviews Drug Discovery2021ReviewDrug Delivery
Michael 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…
Read the article →ACS Nano2021ReviewDrug Delivery
Paula 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…
Read the article →Journal of Materials Chemistry B2021ReviewNon-viral Gene Delivery
Rih-Yang Huang, Zhuo-Hao Liu, Wei-Han Weng, Chien-Wen Chang
Gene therapy requires safe, precise, efficient, and cost-effective delivery. Viral vectors are efficient but face manufacturing, cost, and safety challenges; non-viral vectors are safer and more scalable but often have low delivery efficiency. Magnetic nanoparticles (MNPs) have emerged as a promising strategy to…
Read the article →Advanced Materials2021ReviewNon-viral Gene Delivery
Arun R. K. Kumar, Yufeng Shou, Brian Chan, Krishna L., Andy Tay
This review examines how viral vectors, electroporation, microfluidic systems, nanoparticles and high-aspect-ratio nanostructures can improve the efficiency, viability and scalability of transfecting primary immune cells for applications such as CAR-T, CAR-NK and gene editing. It highlights the trade-offs between…
Read the article →Leukemia2021ResearchDrug Delivery
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 tumour escape and relapse. A modular…
Read the article →Journal of the American Chemical Society (JACS)2021ResearchNon-viral Gene Delivery
Dapeng Zhang, Elena N. Atochina-Vasserman, Devendra S. Maurya, Ning Huang, Qi Xiao, Nathan Ona, Matthew Liu, Hamna Shahnawaz, Houping Ni, Kyunghee Kim, Margaret M. Billingsley, Darrin J. Pochan, Michael J. Mitchell, Drew Weissman, Virgil Percec
Four-component lipid nanoparticles (LNPs) represent the leading non-viral vectors for mRNA delivery, but they have limitations including: (1) segregation of the neutral ionisable lipid as droplets in the LNP core, reducing transfection efficiency to ~1-2%; (2) the "PEG dilemma" where PEGylation increases circulation…
Read the article →Molecular Therapy2021ResearchNon-viral Gene Delivery
Hamideh Parhiz, Jacob S. Brenner, Et Al. (full Author List Not Included In The Supplied Excerpt)
T cells are notoriously resistant to exogenous mRNA transfection, limiting in vivo T cell engineering for immunotherapy, CAR T generation, and HIV cure. A safe, specific, and efficient in vivo mRNA delivery platform for CD4+ T cells was needed. In vitro: anti-CD4/mRNA-LNPs bound specifically to human CD4+ T cells…
Read the article →Advanced Science (Weinh.)2021ResearchNon-viral Gene Delivery
Johan Karlsson, Stephanie Y. Tzeng, Shayan Hemmati, Kathryn M. Luly, Olivia Choi, Yuan Rui, David R. Wilson, Kristen L. Kozielski, Alfredo Quiñones-Hinojosa, Jordan J. Green
Systemic delivery of RNA therapeutics with polymer-based nanocarriers is limited by poor colloidal stability in blood and inefficient intracellular delivery of siRNA to the cytosol. There is a need for nanoparticles that remain stable extracellularly but rapidly release RNA intracellularly. Crosslinking: Molecular…
Read the article →Nanomaterials2021ResearchNon-viral Gene Delivery
Tresa Lopez-Royo, Victor Sebastian, Laura Moreno-Martinez, Laura Uson, Cristina Yus, Teresa Alejo, Pilar Zaragoza, Rosario Osta, Manuel Arruebo, Raquel Manzano
CRISPR/Cas gene-editing components are often encoded on large plasmids (9–19 kb), which are difficult to encapsulate and transfect. Most PLGA nanoparticle (NP) gene-delivery studies use small nucleic acids (siRNA) or small plasmids (<6 kb), and the structural integrity and functional performance of large plasmids in…
Read the article →Materials Science and Engineering: C2021ResearchDrug Delivery
Jiayu Zhou, Yishu Zhai, Jumei Xu, Tian Zhou, Lian Cen
PLGA microspheres are widely used for controlled drug release, but they often exhibit pronounced initial or mid-term burst release. A strategy is needed to finely tune drug release kinetics and suppress burst release, especially for water-soluble drugs. MSNs: Average size 119 nm; specific surface area 902.53 m²/g…
Read the article →Nature Communications2021ResearchNon-viral Gene Delivery
Julia Koerner, Dennis Horvath, Valerie L. Herrmann, Anna Mackeracher, Bruno Gander, Hideo Yagita, Jacques Rohayem, Marcus Groettrup
Cancer immunotherapy needs potent, pharmaceutically defined, GMP-compatible adjuvants for clinical translation. Poly(I:C) is a widely used TLR3 agonist but has ill-defined structure, heterogeneity, pyrogen contamination, and toxicity concerns. Riboxxim is a well-defined 100-bp double-stranded RNA with a…
Read the article →Bioengineering2021ResearchNon-viral Gene Delivery
Rodgers, T., Muzzio, N., Watson, C., & Romero, G. (2021).
Gene-editing tools are large plasmid constructs that cannot spontaneously enter mammalian cells, and viral vectors are limited by cargo size, immunogenicity, and manufacturing challenges. PBAE nanoparticles are promising nonviral carriers, but unmodified PEG-PDHA nanoparticles release encapsulated plasmid DNA too…
Read the article →Biomaterials2021ReviewDrug Delivery
Shepherd Sj, Issadore D, Mitchell Mj.
Nanomedicine translation is limited by non-scalable, batch-variable bulk NP formulation methods that often produce large, polydisperse particles. Microfluidics offers precise control over microscale mixing and nanoprecipitation, enabling more reproducible NPs with controlled size, size distribution, and loading. This…
Read the article →Nature Reviews Drug Discovery2021ReviewNon-viral Gene Delivery
Chaudhary N, Weissman D, Whitehead Ka.
mRNA vaccines have progressed from a scepticism-inducing idea to clinical reality, with COVID-19 catalysing the fastest vaccine development in history. Remaining needs include optimising mRNA design, intracellular delivery, and applications beyond SARS-CoV-2 prophylaxis. This review describes mRNA vaccine…
Read the article →2021ReviewDrug Delivery
Cancer immunotherapy has shown efficacy but is limited by serious adverse effects, nonspecific inflammation, and challenges in spatiotemporal control of immune responses. Nanomedicine and functionalised nanosystems offer programmable pharmacokinetics, co-delivery of immunomodulators, and targeted delivery…
Read the article →2021ReviewDrug Delivery
Venkatas J, Singh M.
Cervical cancer is immunologically relevant because retained high-risk HPV antigens can be recognised as foreign, making immunotherapy attractive. However, conventional immunotherapy is limited by variable efficacy, immune evasion, cytokine toxicity, and poor targeting. Nanomedicine may improve delivery, targeting…
Read the article →Frontiers in Immunology2021ReviewNon-viral Gene Delivery
Balakrishnan Pb, Sweeney Ee.
Adoptive T cell therapy has revolutionized treatment of some hematologic malignancies but remains limited in solid tumours—especially central nervous system (CNS) tumours—by poor intratumoral delivery across anatomical barriers, suboptimal T cell specificity or activation, and intratumoral T cell dysfunction caused…
Read the article →Seminars in Immunology2021ReviewNon-viral Gene Delivery
Est-Witte Se, Livingston Nk, Omotoso Mo, Green Jj, Schneck Jp.
T cell therapies (TIL, TCR, CAR T) show clinical efficacy but are limited by high cost, lengthy ex vivo manufacturing, patient variability, and poor persistence. Nanoparticles offer a modular, universal platform to improve T cell therapy at every stage—from antigen presentation and T cell activation to T cell…
Read the article →Advanced Healthcare Materials2021ReviewNon-viral Gene Delivery
Ho W, Gao M, Li F, Li Z, Zhang X-Q, Xu X.
Nucleic acid vaccines (DNA and mRNA) offer rapid design, adaptability to changing pathogen strains, and stimulation of both humoral and cellular immunity, but their clinical translation is limited by inefficient delivery—nucleic acids are rapidly degraded by endogenous nucleases, have poor cellular uptake due to…
Read the article →Advanced Healthcare Materials2021ReviewNon-viral Gene Delivery
Raza F, Zafar H, Zhang S, Kamal Z, Su J, Yuan W-E, Qiu M.
Cancer immunotherapy is limited by the immunosuppressive tumour microenvironment, patient heterogeneity, poor delivery of immunotherapeutics, and systemic immunotoxicity. Cell membrane-derived biomimetic nanoparticles may improve delivery and biodistribution, enhance targeting and immune stimulation, and overcome…
Read the article →Signal Transduction and Targeted Therapy2021ReviewNon-viral Gene Delivery
Chen L, Hong W, Ren W, Xu T, Qian Z, He Z.
Synthetic nanoparticles face physiological barriers, RES clearance, and unintended biological interactions despite PEGylation and ligand grafting. Biological vectors—cell membranes, extracellular vesicles (EVs), and viruses—offer biocompatibility, biodegradability, immune evasion, and natural targeting. This review…
Read the article →Nature Reviews Materials2021ReviewDrug Delivery
Mandana 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 optimised 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…
Read the article →Bioactive Materials2021ReviewNon-viral Gene Delivery
Muyue Yang, Jipeng Li, Ping Gu, Xianqun Fan
Tumour microenvironment (TME) modulation is a promising strategy in cancer immunotherapy, but conventional immunotherapeutic agents suffer from limited drug retention in the TME, severe adverse events, and low response rates. Nanoparticles can prolong retention, enable targeted delivery to TME components, and convert…
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…
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