Nanocarriers with tunable surface properties to unblock bottlenecks in systemic drug and gene delivery

Zou, Haijuan; Wang, Zhongjuan; Feng, Min

doi:10.1016/j.jconrel.2015.07.014

Cited by 51 publications

(38 citation statements)

References 115 publications

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“…19,20 In general, zwitterionic coronas have been shown to improve in vitro stability, cell uptake, and pharmacokinetics of some nano-carriers relative to both PEGylated and unmodified carriers. 21,22 …”

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confidence: 99%

Zwitterionic Nanocarrier Surface Chemistry Improves siRNA Tumor Delivery and Silencing Activity Relative to Polyethylene Glycol

et al. 2017

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Although siRNA-based nanomedicines hold promise for cancer treatment, conventional siRNA–polymer complex (polyplex) nanocarrier systems have poor pharmacokinetics following intravenous delivery, hindering tumor accumulation. Here, we determined the impact of surface chemistry on the in vivo pharmacokinetics and tumor delivery of siRNA polyplexes. A library of diblock polymers was synthesized, all containing the same pH-responsive, endosomolytic polyplex core-forming block but different corona blocks: 5 kDa (benchmark) and 20 kDa linear polyethylene glycol (PEG), 10 kDa and 20 kDa brush-like poly(oligo ethylene glycol), and 10 kDa and 20 kDa zwitterionic phosphorylcholine-based polymers (PMPC). In vitro, it was found that 20 kDa PEG and 20 kDa PMPC had the highest stability in the presence of salt or heparin and were the most effective at blocking protein adsorption. Following intravenous delivery, 20 kDa PEG and PMPC coronas both extended circulation half-lives 5-fold compared to 5 kDa PEG. However, in mouse orthotopic xenograft tumors, zwitterionic PMPC-based polyplexes showed highest in vivo luciferase silencing (>75% knockdown for 10 days with single IV 1 mg/kg dose) and 3-fold higher average tumor cell uptake than 5 kDa PEG polyplexes (20 kDa PEG polyplexes were only 2-fold higher than 5 kDa PEG). These results show that high molecular weight zwitterionic polyplex coronas significantly enhance siRNA polyplex pharmacokinetics without sacrificing polyplex uptake and bioactivity within tumors when compared to traditional PEG architectures.

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confidence: 99%

Zwitterionic Nanocarrier Surface Chemistry Improves siRNA Tumor Delivery and Silencing Activity Relative to Polyethylene Glycol

et al. 2017

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“…In order to reach widespread cancer cells, molecular drugs must be specifically directed and protected from natural and tumor-related barriers while in vascular circulation. To this end, over the last few years biomedicine has turned to the use of nanomaterials as smart drug-carriers, although the clinical outcome in treating these diseases is still far from optimal [80][81][82]. In this regard, a large number of biomaterials that are considered to be effective drug-delivery systems on the nanoscale can be found in the literature [83][84][85].…”

Section: Nanoparticle-based Devices For Drug Deliverymentioning

confidence: 99%

Elastin-like polypeptides in drug delivery

Rodríguez‐Cabello

Arias

Rodrigo

et al. 2016

Advanced Drug Delivery Reviews

140

112

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The use of recombinant elastin-like materials, or elastin-like recombinamers (ELRs), in drug-delivery applications is reviewed in this work. Although ELRs were initially used in similar ways to other, more conventional kinds of polymeric carriers, their unique properties soon gave rise to systems of unparalleled functionality and efficiency, with the stimuli responsiveness of ELRs and their ability to self-assemble readily allowing the creation of advanced systems. However, their recombinant nature is likely the most important factor that has driven the current breakthrough properties of ELR-based delivery systems. Recombinant technology allows an unprecedented degree of complexity in macromolecular design and synthesis. In addition, recombinant materials easily incorporate any functional domain present in natural proteins. Therefore, ELR-based delivery systems can exhibit complex interactions with both their drug load and the tissues and cells towards which this load is directed. Selected examples, ranging from highly functional nanocarriers to macrodepots, will be presented.

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“…The surface, size and shape of the nanoparticles are preponderant for their endurance across the circulatory system (reviewed in [40]). Neutral or slightly negative surfaces assure low adsorption to blood proteins, such as opsonins, and avoid phagocytosis (reviewed in [40,41]). Hence, neutralization of charged nanoparticles may be achieved by coating with hydrophilic polymers such as polyethylene glycol (PEG), polyglycerol (PG), or polysaccharides, such as heparan or chitosan, with zwitterionic ligands, such as carboxybetaines or sulfobetaines, with mercaptoalkyl acid ligands, such as 11-mercaptoundecanoic acid (MUA), or even with proteins and lipids (reviewed in [40,42]).…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, for gene therapy it is necessary that the vector and payload pass across the complex hydrophobic layer of the tumor cell membrane [41]. This mainly occurs via endocytosis mediated by ligand-receptor specific, using active targeting, or non-specific, such as electrostatic or hydrophobic, interactions with the cell membrane (reviewed in [40,65,66]).…”

Section: Introductionmentioning

confidence: 99%

Gene Therapy in Cancer Treatment: Why Go Nano?

et al. 2020

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The proposal of gene therapy to tackle cancer development has been instrumental for the development of novel approaches and strategies to fight this disease, but the efficacy of the proposed strategies has still fallen short of delivering the full potential of gene therapy in the clinic. Despite the plethora of gene modulation approaches, e.g., gene silencing, antisense therapy, RNA interference, gene and genome editing, finding a way to efficiently deliver these effectors to the desired cell and tissue has been a challenge. Nanomedicine has put forward several innovative platforms to overcome this obstacle. Most of these platforms rely on the application of nanoscale structures, with particular focus on nanoparticles. Herein, we review the current trends on the use of nanoparticles designed for cancer gene therapy, including inorganic, organic, or biological (e.g., exosomes) variants, in clinical development and their progress towards clinical applications.

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Nanocarriers with tunable surface properties to unblock bottlenecks in systemic drug and gene delivery

Cited by 51 publications

References 115 publications

Zwitterionic Nanocarrier Surface Chemistry Improves siRNA Tumor Delivery and Silencing Activity Relative to Polyethylene Glycol

Zwitterionic Nanocarrier Surface Chemistry Improves siRNA Tumor Delivery and Silencing Activity Relative to Polyethylene Glycol

Elastin-like polypeptides in drug delivery

Gene Therapy in Cancer Treatment: Why Go Nano?

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