Micro‐ and Nanotechnologies for Intracellular Delivery

Li, Yan; Zhang, Jinfeng; Lee, Chun‐Sing; Chen, Xianfeng

doi:10.1002/smll.201401532

Cited by 71 publications

(65 citation statements)

References 175 publications

(284 reference statements)

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“…While intracellular delivery of functional proteins offers tremendous therapeutic potential, 28,29 the difficulty of rapid cytosolic delivery of proteins in active conformation is massive and still represents an unmet challenge. 30,31 …”

Section: Introductionmentioning

confidence: 99%

Nanomotor-Enabled pH-Responsive Intracellular Delivery of Caspase-3: Toward Rapid Cell Apoptosis

et al. 2017

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Direct and efficient intracellular delivery of enzymes to cytosol holds tremendous therapeutic potential while remaining an unmet technical challenge. Herein, an ultrasound (US)-propelled nanomotor approach and a high pH-responsive delivery strategy is reported to overcome such challenge using caspase-3 (CASP-3) as a model enzyme. Consisting of a gold nanowire (AuNW) motor with a pH-responsive polymer coating, in which the CASP-3 is loaded, the resulting nanomotor protects the enzyme from release and deactivation prior to reaching an intracellular environment. However, upon entering a cell and exposure to the higher intracellular pH, the polymer coating is dissolved, thereby directly releasing the active CASP-3 enzyme to the cytosol and causing rapid cell apoptosis. In vitro studies using gastric cancer cells as a model cell line demonstrates that such motion-based active delivery approach leads to remarkably high apoptosis efficiency within significantly shorter time and lower amount of CASP-3 compared to other control groups without involving US-propelled nanomotors. For instance, the reported nanomotor system can achieve 80% apoptosis of human gastric adenocarcinoma (AGS) cells within only 5 min, which dramatically outperforms other CASP-3 delivery approaches. These results indicate that the US-propelled nanomotors may act as a powerful vehicle for cytosolic delivery of active therapeutic proteins, which would offer an attractive means to enhance the current landscape of intracellular protein delivery and therapy. While CASP-3 is selected as a model protein in this study, the same nanomotor approach can be readily applied to a variety of different therapeutic proteins.

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Section: Introductionmentioning

confidence: 99%

Nanomotor-Enabled pH-Responsive Intracellular Delivery of Caspase-3: Toward Rapid Cell Apoptosis

et al. 2017

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“…With the rapid advances of nanotechnology, versatile NP systems including semiconducting quantum dots (QDs), gold NPs, and dye encapsulated NPs, etc., have been developed 12, 13, 14, 15, 16. Despite the fact that NPs with varied sizes have been designed for different biomedical applications,17, 18, 19 there has been limited success in highly selective cancer targeting, and only a few examples for inorganic gold NPs were reported 16, 20. This is attributed to the precise size control of inorganic NPs to be smaller than 10 nm, as NPs with sizes ranging from 20 to 200 nm are able to be nonspecific internalized into cells which significantly compromises the detection selectivity 21, 22, 23, 24, 25.…”

Section: Introductionmentioning

confidence: 99%

Ultrasmall Conjugated Polymer Nanoparticles with High Specificity for Targeted Cancer Cell Imaging

Feng

Liu

et al. 2017

Advanced Science

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Fluorescent and biocompatible organic nanoparticles have attracted great interest in cancer detection and imaging, but the nonspecific cellular uptake has limited the detection specificity and sensitivity. Herein, the authors report the ultrasmall conjugated polymer nanoparticles (CPNs) with bright far‐red/near‐infrared emission for targeted cancer imaging with high specificity. The sizes of the ultrasmall CPNs are around 6 nm (CPN6), while large CPNs show sizes around 30 nm (CPN30). Moreover, CPN6 exhibits largely improved fluorescence quantum yield (η) of 41% than CPN30 (25%). Benefiting from the ultrasmall size, bare CPN6 shows largely suppressed nonspecific cellular uptake as compared to CPN30, while cyclic arginine‐glycine‐aspartic acid (cRGD) functionalized CPN6 (cRGD‐CPN6) possesses excellent selectivity toward αvβ 3 integrin overexpressed MDA‐MB‐231 cells over other cells in cell mixtures. The faster body clearance of CPN6 over CPN30 indicates its greater potentials as a noninvasive nanoprobe for in vivo and practical applications.

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“…22,27,28 Diamond, due to its high mechanical toughness, ensures the mechanical strength of nanoneedles with nanometer scale. Additionally, diamond is chemically inert and biocompatible, features allowing its safe application to cells.…”

Section: In Vitro Applicationsmentioning

confidence: 99%

Physical Delivery of Macromolecules using High-Aspect Ratio Nanostructured Materials

Lee¹,

Lingampalli²,

Pisano

et al. 2015

ACS Appl. Mater. Interfaces

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There is great need for the development of an efficient delivery method of macromolecules, including nucleic acids, proteins, and peptides, to cell cytoplasm without eliciting toxicity or changing cell behavior. High-aspect ratio nanomaterials have addressed many challenges present in conventional methods, such as cell membrane passage and endosomal degradation, and have shown the feasibility of efficient high-throughput macromolecule delivery with minimal perturbation of cells. This review describes the recent advances of in vitro and in vivo physical macromolecule delivery with high-aspect ratio nanostructured materials and summarizes the synthesis methods, material properties, relevant applications, and various potential directions.

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Micro‐ and Nanotechnologies for Intracellular Delivery

Cited by 71 publications

References 175 publications

Nanomotor-Enabled pH-Responsive Intracellular Delivery of Caspase-3: Toward Rapid Cell Apoptosis

Nanomotor-Enabled pH-Responsive Intracellular Delivery of Caspase-3: Toward Rapid Cell Apoptosis

Ultrasmall Conjugated Polymer Nanoparticles with High Specificity for Targeted Cancer Cell Imaging

Physical Delivery of Macromolecules using High-Aspect Ratio Nanostructured Materials

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