Cationic Shell-Cross-Linked Knedel-like (cSCK) Nanoparticles for Highly Efficient PNA Delivery

Fang, Huafeng; Zhang, Ke; Shen, Gang; Wooley, Karen L.; Taylor, John‐Stephen

doi:10.1021/mp800199w

Cited by 53 publications

(70 citation statements)

References 37 publications

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“…[4,5] For example, shell-cross-linked nanoparticles (SCKs) have been pioneered by Wooley's and other groups since the late 1990s for various applications, e.g., drug and gene delivery. [6,7] However, in another consideration, it is expected that drugs encapsulated in micelles can be specifically and more rapidly released in the interior of targeted cells to enhance their functions. [8][9][10] Maintenance of cross-linkages of the micellar shell may indeed act as a barrier to intracellular drug release.…”

Section: Introductionmentioning

confidence: 99%

Core–Shell–Corona Micelle Stabilized by Reversible Cross‐Linkage for Intracellular Drug Delivery

Wang

Sun

et al. 2010

Macromol. Rapid Commun.

121

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Reversibly cross-linked core-shell-corona micelles based on a triblock copolymer composed of poly(aliphatic ester), polyphosphoester, and poly(ethylene glycol) are reported. The triblock copolymer is synthesized through consecutive ring-opening polymerization of ε-caprolactone and 2,4-dinitrophenylthioethyl ethylene phosphate, followed by conjugation of poly(ethylene glycol). After deprotection under mild conditions, the amphiphilic polymer forms core-shell-corona micelles with free thiols in the shell. Cross-linking of the micelles within the shell reduces their critical micellization concentration and enhances their stability against severe conditions. The redox-sensitive cross-linkage allows the facilitated release of entrapped anticancer drugs in the cytoplasm in response to the intracellular reductive environment. With enhanced stability during circulation after administration, and accelerated intracellular drug release at the target site, the biocompatible and biodegradable shell-cross-linked polymeric micelle is promising as a drug vehicle for cancer chemotherapy.

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Section: Introductionmentioning

confidence: 99%

Core–Shell–Corona Micelle Stabilized by Reversible Cross‐Linkage for Intracellular Drug Delivery

Wang

Sun

et al. 2010

Macromol. Rapid Commun.

121

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“…N-Hydroxybenzotriazole H 2 O (HOBT) and 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) were purchased from EMD Chemicals, Inc. The amphiphilic block copolymer, poly(acrylic acid) 60 -block-polystyrene 30 (PAA 60 -b-PS 30 ), was prepared according to literature [33], and transformed into poly(acrylamidoethylamine) 160 -block-polystyrene 30 (PAEA 160 -b-PS 30 ) for the preparation of the cSCKs [44]. CellTiter 96 non-radioactive cell proliferation assay was purchased from Promega.…”

Section: Methodsmentioning

confidence: 99%

“…ODN hybrids and DNA by an endocytotic mechanism [33]. By adjusting the N/P ratio, the cSCK binding affinity could be optimized for the binding and delivery of the PNA-YR 9 .…”

Section: Rsfsroyalsocietypublishingorg Interface Focus 3: 20120059mentioning

confidence: 99%

Antisense peptide nucleic acid-functionalized cationic nanocomplex for in vivo mRNA detection

et al. 2013

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One contribution of 10 to a Theme Issue 'Molecular-, nano-and micro-devices for real-time in vivo sensing'. Acute lung injury (ALI) is a complex syndrome with many aetiologies, resulting in the upregulation of inflammatory mediators in the host, followed by dyspnoea, hypoxemia and pulmonary oedema. A central mediator is inducible nitric oxide synthase (iNOS) that drives the production of NO and continued inflammation. Thus, it is useful to have diagnostic and therapeutic agents for targeting iNOS expression. One general approach is to target the precursor iNOS mRNA with antisense nucleic acids. Peptide nucleic acids (PNAs) have many advantages that make them an ideal platform for development of antisense theranostic agents. Their membrane impermeability, however, limits biological applications. Here, we report the preparation of an iNOS imaging probe through electrostatic complexation between a radiolabelled antisense PNA-YR 9 . oligodeoxynucleotide (ODN) hybrid and a cationic shell-crosslinked knedel-like nanoparticle (cSCK). The Y (tyrosine) residue was used for 123 I radiolabelling, whereas the R 9 (arginine 9 ) peptide was included to facilitate cell exit of untargeted PNA. Complete binding of the antisense PNA-YR 9 . ODN hybrid to the cSCK was achieved at an 8 : 1 cSCK amine to ODN phosphate (N/P) ratio by a gel retardation assay. The antisense PNA-YR 9 . ODN . cSCK nanocomplexes efficiently entered RAW264.7 cells, whereas the PNA-YR 9 . ODN alone was not taken up. Low concentrations of 123 I-labelled antisense PNA-YR 9 . ODN complexed with cSCK showed significantly higher retention of radioactivity when iNOS was induced in lipopolysaccharide þ interferon-g-activated RAW264.7 cells when compared with a mismatched PNA. Moreover, statistically, greater retention of radioactivity from the antisense complex was also observed in vivo in an iNOS-induced mouse lung after intratracheal administration of the nanocomplexes. This study demonstrates the specificity and sensitivity by which the radiolabelled nanocomplexes can detect iNOS mRNA in vitro and in vivo and their potential for early diagnosis of ALI.

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“…Having the antisense agent covalently bound to the NP runs the risk, however, that much of it may remain trapped in endosomes along with the NP. This appeared to be the case in a study with shell cross-linked NP linked to antisense PNAs via an amide linkage that did not show bioactivity, whereas the same PNAs linked via a bioreductively cleavable disulfide linker did [130]. confocal studies showed that while the PNA was able to exit the endocytic compartments and enter the cytoplasm, the NP was not.…”

Section: Antisense Imaging Agent Deliverymentioning

confidence: 97%

Imaging Genetic Information

Taylor

2014

Nanotechnology for Biomedical Imaging and Diagnostics

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Cationic Shell-Cross-Linked Knedel-like (cSCK) Nanoparticles for Highly Efficient PNA Delivery

Cited by 53 publications

References 37 publications

Core–Shell–Corona Micelle Stabilized by Reversible Cross‐Linkage for Intracellular Drug Delivery

Core–Shell–Corona Micelle Stabilized by Reversible Cross‐Linkage for Intracellular Drug Delivery

Antisense peptide nucleic acid-functionalized cationic nanocomplex for in vivo mRNA detection

Imaging Genetic Information

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