Journal of Controlled Release2020ResearchNon-viral Gene Delivery
Nour Shobaki, Yusuke Sato, Yuichi Suzuki, Nana Okabe, Hideyoshi Harashima
Tumour-associated macrophages (TAMs) are largely M2-like and promote tumour growth, angiogenesis, metastasis, and immune suppression. There is a need for systemic delivery systems that can target TAMs and manipulate their pro-tumour functions with siRNA for cancer immunotherapy. Optimised CL4H6-LNPs had 90% siRNA…
Read the article →Science Advances2020ResearchNon-viral Gene Delivery
Elana 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)…
Read the article →ACS Applied Bio Materials2020ResearchNon-viral Gene Delivery
Coralie M. Backlund, Christopher R. Hango, Lisa M. Minter, Gregory N. Tew
Intracellular protein and antibody delivery is limited by inefficient carriers, high toxicity, and a frequent requirement for serum-free conditions, especially in difficult-to-transfect cells such as immune cells, stem cells, and neurons. A simple noncovalent carrier that works in complete media and across diverse…
Read the article →Frontiers in Bioengineering and Biotechnology2020ResearchDrug Delivery
Serkan Yaman, Harish Ramachandramoorthy, Gizem Oter, Daria Zhukova, Tam Nguyen, Manoj K. Sabnani, Jon A. Weidanz, Kytai T. Nguyen
Melanoma is an aggressive skin cancer with limited treatment efficacy due to non-specific drug targeting, severe side effects, and multidrug resistance. Current cell-based immunotherapies are costly, complex, and carry long-term autoimmune risks. There is a need for a targeted, biocompatible drug delivery system that…
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 →Nanomaterials2020ReviewDrug Delivery
Fam 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…
Read the article →Bioconjugate Chemistry2020ReviewNon-viral Gene Delivery
Francia V, Schiffelers Rm, Cullis Pr, Witzigmann D
LNPs are clinically advanced vectors for siRNA, mRNA, and DNA delivery, but their in vivo behaviour is strongly influenced by the biological environment. Upon administration, biomolecules adsorb to the LNP surface and form a “biomolecular corona,” which defines the particle’s biological identity, affects stability…
Read the article →Nanoscale2019ResearchNon-viral Gene Delivery
Dongyu Chen, Neha Parayath, Shanthi Ganesh, Weimin Wang, Mansoor Amiji
The protein corona that forms on lipid nanoparticles (LNPs) after systemic administration can alter their biological identity, but its impact on tumour delivery is not well understood. This study aimed to determine whether LNP formulation composition and surface charge can manipulate the protein corona and thereby…
Read the article →Nanoscale2019ResearchNon-viral Gene Delivery
Dongyu Chen, Shanthi Ganesh, Weimin Wang, Mansoor Amiji
Protein corona formation in biological fluids can alter nanoparticle cellular uptake, transfection, and gene silencing, but the relationship between LNP surface chemistry and corona-mediated delivery is incompletely understood. This study examined how PEG lipid chain length and PEG molar ratio affect protein corona…
Read the article →Journal of Controlled Release2019ResearchNon-viral Gene Delivery
Yusuke Sato, Kazuki Hashiba, Kosuke Sasaki, Masatoshi Maeki, Manabu Tokeshi, Hideyoshi Harashima
Endosomal escape remains a major rate-limiting step for siRNA delivery. The structure–activity relationships (SAR) of pH-sensitive cationic lipids were incompletely understood, limiting rational design of lipid nanoparticles (LNPs) for efficient in vivo siRNA delivery to hepatocytes. Hydrophilic head group structure…
Read the article →Nature Communications2019ResearchNon-viral Gene Delivery
Francesca Giulimondi, Luca Digiacomo, Daniela Pozzi, Sara Palchetti, Elisabetta Vulpis, Anna Laura Capriotti, Riccardo Zenezini Chiozzi, Aldo Laganà, Heinz Amenitsch, Laura Masuelli, Giovanna Peruzzi, Morteza Mahmoudi, Isabella Screpanti, Alessandra Zingoni
Liposome clinical translation is limited by opsonisation and rapid clearance by immune cells. Although the protein corona is recognised as the liposome’s “biological identity,” it was unclear whether pre-adsorbed corona proteins could help liposomes avoid capture by circulating leukocytes in whole blood and thereby…
Read the article →International Journal of Pharmaceutics (inferred; the supplied PDF is marked “2019ResearchNon-viral Gene Delivery
Yingqi Xu, Dingxin Liu, Jie Hu, Peirong Ding, Meiwan Chen
Triple-negative breast cancer (TNBC) lacks effective targeted therapy. Nonviral co-delivery of an anticancer drug and a therapeutic gene may improve treatment, but efficient tumour-targeted co-delivery remains challenging. TRAIL has shown limited clinical benefit alone, and embelin (EMB) can inhibit XIAP to promote…
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 →Nanoscale2019ReviewDrug Delivery
Ferrari, R.; Sponchioni, M.; Morbidelli, M.; Moscatelli, D
Many polymer-based nanoparticle formulations fail before or during clinical trials. This review identifies the key checkpoints a nanocarrier must satisfy after intravenous injection — biocompatibility, drug loading/release, storage stability, biodistribution, target selectivity, cellular internalisation, and…
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 →Proceedings of the National Academy of Sciences (PNAS)2018ResearchNon-viral Gene Delivery
Ole A. W. Haabeth, Timothy R. Blake, Colin J. Mckinlay, Robert M. Waymouth, Paul A. Wender, Ronald Levy
mRNA-based cancer vaccination is a promising approach for personalised immunotherapy, but safe and effective mRNA delivery remains a major challenge due to mRNA's instability and poor cell membrane permeability. While lipid nanoparticles (LNPs) are the primary delivery strategy, they have limitations with respect to…
Read the article →Molecular Therapy2018ResearchNon-viral Gene Delivery
Daniel L. Jasinski, Hui Li, Peixuan Guo
Drugs with ideal pharmacokinetic profiles require long half-lives but little organ accumulation. Generally, these factors are contradictory: smaller particles lead to faster excretion and shorter half-lives, while larger particles lead to longer circulation but stronger organ accumulation and potential toxicity. The…
Read the article →Toxicology Research (RSC)2018ResearchNon-viral Gene Delivery
Shaohui Cui, Yueying Wang, Yan Gong, Xiao Lin, Yinan Zhao, Defu Zhi, Quan Zhou, Shubiao Zhang
Cationic lipids are widely used non-viral gene delivery vectors, but their toxicity remains a major bottleneck for clinical translation. Cytotoxicity is strongly associated with the cationic headgroup structure, yet the relationship between headgroup chemistry and toxic mechanisms has been rarely studied. IC50…
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 →International Journal of Pharmaceutics2018ResearchNon-viral Gene Delivery
Haimanti Mandal, Sameer S. Katiyar, Rajan Swami, Varun Kushwah, Parmeshwar B. Katare, Anand Kumar Meka, Sanjay K. Banerjee, Amirali Popat, Sanyog Jain
Non-viral gene delivery vectors are safer than viral vectors but often suffer from lower transfection efficiency and cytotoxicity. ε-Poly-L-lysine (ε-PLL) is a naturally occurring, FDA GRAS cationic polymer with low molecular weight and potential for low toxicity, but its use as a pDNA nanocarrier for efficient in…
Read the article →Biomacromolecules2018ResearchDrug Delivery
Jayoung Kim, James G. Shamul, Sagar R Shah, Alyssa Shin, Ben J Lee, Alfredo Quiñones‐hinojosa, Jordan J. Green
Many anticancer small molecules have poor aqueous solubility, and verteporfin (VP) has mainly been used as a photodynamic therapy agent, which carries photosensitivity and delivery limitations. PBAE-based materials have been developed extensively for nucleic acid delivery but are less explored for non-genetic…
Read the article →Journal of Controlled Release.2018ReviewDrug Delivery
Hassan Dianat‐moghadam, Maryam Heidarifard, Rana Jahanban‐esfahlan, Yunes Panahi, Hamed Hamishehkar, Farhad Pouremamali, Reza Rahbarghazi, Mohammad Nouri
Cancer stem cells (CSCs) drive tumour heterogeneity, drug resistance, recurrence, and metastasis, limiting conventional chemo/radiotherapy. Liposomal drug delivery systems (LDDSs) are biocompatible, versatile nanocarriers that may overcome CSC-mediated resistance, but their clinical translation remains limited by…
Read the article →Frontiers in Pharmacology2018ReviewDrug Delivery
Sima Rezvantalab, Natascha Ingrid Drude, Mostafa Keshavarz Moraveji, Nihan Güvener, Emily Kate Koons, Yang Shi, Twan Lammers, Fabian Kiessling
PLGA-based nanoparticles are widely investigated for cancer therapy, but their clinical translation remains limited. A consolidated overview was needed of how PLGA NP physicochemical properties, biological behaviour, targeting strategies, and combination therapies interact—and why promising preclinical results have…
Read the article →Nature Nanotechnology2017ResearchNon-viral Gene Delivery
Tyrel T. Smith, Sirkka B. Stephan, Howell F. Moffett, Laura E. Mcknight, Weihang Ji, Diana Reiman, Emmy Bonagofski, Martin E. Wohlfahrt, Smitha P. S. Pillai, Matthias T. Stephan
Adoptive T cell therapy with CAR-engineered T cells has shown impressive clinical results, but the ex vivo manufacturing process is complex, expensive, and requires specialised facilities, limiting widespread application. A method to programme circulating T cells directly in vivo with tumour-recognising capabilities…
Read the article →