A Photoactivatable AIE Polymer for Light‐Controlled Gene Delivery: Concurrent Endo/Lysosomal Escape and DNA Unpacking

Yuan, Youyong; Zhang, Chong‐Jing; Liu, Bin

doi:10.1002/anie.201503640

Cited by 228 publications

(131 citation statements)

References 35 publications

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“…Unlike other cationic vectors, these vectors induced little toxicity to cells, as well as normal organs (heart, live, kidney, lung, and spleen), thereby suggesting their better biocompatibility. Conventional vectors render gene escape from lysosomes to cytoplasm of target cells via a mechanism of “proton sponge effect,”26 yet this escape efficiency is extremely low at only 1–2% 12. Moreover, this process results in rupture of the lysosome membrane and, in turn, induces cytotoxicity 27.…”

Section: Discussionmentioning

confidence: 99%

Rod‐Shaped Active Drug Particles Enable Efficient and Safe Gene Delivery

et al. 2017

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Efficient microRNAs (miRNA) delivery into cells is a promising strategy for disease therapy, but is a major challenge because the available conventional nonviral vectors have significant drawbacks. In particular, after these vectors are entrapped in lysosomes, the escape efficiency of genes from lysosomes into the cytosol is less than 2%. Here, a novel approach for lethal‐7a (let‐7a) replacement therapy using rod‐shaped active pure drug nanoparticles (≈130 nm in length, PNPs) with a dramatically high drug‐loading of ≈300% as vectors is reported. Importantly, unlike other vectors, the developed PNPs/let‐7a complexes (≈178 nm, CNPs) can enter cells and bypass the lysosomal route to localize to the cytosol, achieving efficient intracellular delivery of let‐7a and a 50% reduction in expression of the target protein (KRAS). Also, CNPs prolong the t 1/2 of blood circulation by ≈threefold and increase tumor accumulation by ≈1.5–2‐fold, resulting in significantly improved antitumor efficacies. Additionally, no damage to normal organs is observed following systemic injection of CNPs. In conclusion, rod‐shaped active PNPs enable efficient and safe delivery of miRNA with synergistic treatment for disease. This nanoplatform would also offer a viable strategy for the potent delivery of proteins and peptides in vitro and in vivo.

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Section: Discussionmentioning

confidence: 99%

Rod‐Shaped Active Drug Particles Enable Efficient and Safe Gene Delivery

et al. 2017

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“…Provided that the degradation can be precisely limited within the diseased lesions, ZnO with cytotoxic effects can act as therapeutic agents. More importantly, by introducing ROS‐cleavable linker (e.g., thioketal, aminocrylate), the resultant reactive intermediate (ROS) can further undergo the cascade reaction to activate the caged cargoes desirably. Inspired from this intracellular cascade reaction, ZnO‐based nanoplatform offers the opportunity for sophisticated in‐situ drug release to improve the therapeutic index of drugs with high efficiency.…”

Section: Introductionmentioning

confidence: 99%

Programmed Nanococktail for Intracellular Cascade Reaction Regulating Self‐Synergistic Tumor Targeting Therapy

Chen

Luo

Qiu

et al. 2015

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In this work, a ZnO based nanococktail with programmed functions is designed and synthesized for self-synergistic tumor targeting therapy. The nanococktail can actively target tumors via specific interaction of hyaluronic acid (HA) with CD44 receptors and respond to HAase-rich tumor microenvironment to induce intracellular cascade reaction for controlled therapy. The exposed cell-penetrating peptide (R8) potentiates the cellular uptake of therapeutic nanoparticles into targeted tumor cells. Then ZnO cocktail will readily degrade in acidic endo/lysosomes and induce the production of desired reactive oxygen species (ROS) in situ. The destructive ROS not only leads to serious cell damage but also triggers the on-demand drug release for precise chemotherapy, thus achieving enhanced antitumor efficiency synergistically. After tail vein injection of ZnO cocktail, a favorable tumor apoptosis rate (71.2 ± 8.2%) is detected, which is significantly superior to that of free drug, doxorubicin (12.9 ± 5.2%). Both in vitro and in vivo studies demonstrate that the tailor-made ZnO cocktail with favorable biocompatibility, promising tumor specificity, and self-synergistically therapeutic capacity opens new avenues for cancer therapy.

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“…Compared with other fluorophores such as small molecules and quantum dots, they are advantageous as biomaterials because of their good biocompatibility, ease of preparation, and biomimetic character (4)(5)(6). Conventional fluorophores show good emission in dilute solution but experience varying degrees of aggregation-caused quenching due to the intense intermolecular interactions, which will decay or relax the excited state back to the ground state via nonradiative channels (7).…”

mentioning

confidence: 99%

Fluorescent metallacycle-cored polymers via covalent linkage and their use as contrast agents for cell imaging

Zhang

Shu-ya

Yan

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

111

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The covalent linkage of supramolecular monomers provides a powerful strategy for constructing dynamic polymeric materials whose properties can be readily tuned either by the selection of monomers or the choice of functional linkers. In this strategy, the stabilities of the supramolecular monomers and the reactions used to link the monomers are crucial because such monomers are normally dynamic and can disassemble during the linking process, leading to mixture of products. Therefore, although noncovalent interactions have been widely introduced into metallacycle structures to prepare metallosupramolecular polymers, metallacyclecored polymers linked by covalent bonds have been rarely reported. Herein, we used the mild, highly efficient amidation reaction between alkylamine and N-hydroxysuccinimide-activated carboxylic acid to link the pendent amino functional groups of a rhomboidal metallacycle 10 to give metallacycle-cored polymers P1 and P2, which further yielded nanoparticles at low concentration and transformed into network structures as the concentration increased. Moreover, these polymers exhibited enhanced emission and showed better quantum yields than metallacycle 10 in methanol and methanol/water (1/9, vol/vol) due to the aggregationinduced emission properties of a tetraphenylethene-based pyridyl donor, which serves as a precursor for metallacycle 10. The fluorescence properties of these polymers were further used in cell imaging, and they showed a significant enrichment in lung cells after i.v. injection. Considering the anticancer activity of rhomboidal Pt(II) metallacycles, this type of fluorescent metallacycle-cored polymers can have potential applications toward lung cancer treatment.fluorescent polymers | supramolecular coordination complex | covalent linkage | aggregation-induced emission | cell imaging F luorescent polymers have received much attention in the chemical and life sciences due to their promising applications in biological labeling, tracking, monitoring, imaging, and diagnostics (1-3). Compared with other fluorophores such as small molecules and quantum dots, they are advantageous as biomaterials because of their good biocompatibility, ease of preparation, and biomimetic character (4-6). Conventional fluorophores show good emission in dilute solution but experience varying degrees of aggregation-caused quenching due to the intense intermolecular interactions, which will decay or relax the excited state back to the ground state via nonradiative channels (7). Such fluorophores are not ideal candidates for the preparation of fluorescent polymers, because they need to be aggregated by the polymerization process, which will more or less decrease the fluorescence emissions and the quantum yields of the derived fluorescent polymers.In 2001, Tang and coworkers (8) reported an opposite fluorescence effect named as aggregation-induced emission (AIE). In such cases, fluorophores are nearly nonemissive as discrete molecules, but they exhibit strong fluorescence in concentrated solution or in the s...

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A Photoactivatable AIE Polymer for Light‐Controlled Gene Delivery: Concurrent Endo/Lysosomal Escape and DNA Unpacking

Cited by 228 publications

References 35 publications

Rod‐Shaped Active Drug Particles Enable Efficient and Safe Gene Delivery

Rod‐Shaped Active Drug Particles Enable Efficient and Safe Gene Delivery

Programmed Nanococktail for Intracellular Cascade Reaction Regulating Self‐Synergistic Tumor Targeting Therapy

Fluorescent metallacycle-cored polymers via covalent linkage and their use as contrast agents for cell imaging

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