Biomimetic Nanocarrier for Direct Cytosolic Drug Delivery

Zhang, Zhihong; Cao, Weiguo; Jin, Honglin; Lovell, Jonathan F.; Yang, Mi; Ding, Lili; Chen, Juan; Corbin, Ian R.; Luo, Qingming; Zheng, Gang

doi:10.1002/anie.200903112

Cited by 150 publications

(105 citation statements)

References 38 publications

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“…This might indicate that uptake mechanism of RLNs was a combination of direct transmembrane delivery (Type I or III) and endocytic pathway (Type II or III). Native apolipoprotein mixture, including apoA-I, apoB-100, and apoE, was introduced to insert into the lipid core of RLNs, which was favorable for SR-BI-mediated non-aqueous pathway [40,42] and other lipoprotein receptor-associated endocytic internalization pathways [43]. Results from this study hence supported the hypothesis that cellular internalization of RLNs involved multiple-receptor mediated mechanisms via endogenous apolipoproteins.…”

Section: Multiple Receptor-mediated Cellular Internalization Mechanismsupporting

confidence: 73%

“…These classes of apolipoproteins interacted either with the scavenger receptor class B type I (SR-BI) (apoA-I) [38] or with the LDL-related receptors (LDLR/LRP) (apoB and E) [39], which are multifunctional, multi-ligand scavenger and signaling receptors. This bio-derived receptor-mediated multiple-targeting system would be beneficial to transporting cytosolic PTX encapsulated in the RLNs, since receptors in HepG2 cells could readily recognize apolipoproteins of the nanoparticles, subsequently undergoing membrane reorganization and cellular internalization, eventually leading to enhanced drug targeting for increased antitumor efficacy [40,41].…”

Section: Multiple Receptor-mediated Cellular Internalization Mechanismmentioning

confidence: 99%

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Green design “bioinspired disassembly-reassembly strategy” applied for improved tumor-targeted anticancer drug delivery

Wang

Zhou

et al. 2016

Journal of Controlled Release

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Section: Multiple Receptor-mediated Cellular Internalization Mechanismsupporting

confidence: 73%

Section: Multiple Receptor-mediated Cellular Internalization Mechanismmentioning

confidence: 99%

Green design “bioinspired disassembly-reassembly strategy” applied for improved tumor-targeted anticancer drug delivery

Wang

Zhou

et al. 2016

Journal of Controlled Release

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“…The siRNA fluorescence was evenly distributed within whole cell cytosol further demonstrating that NPSC mediated siRNA delivery enter cells bypassing endo/lysosomes. [21] …”

mentioning

confidence: 99%

Direct Cytosolic Delivery of siRNA Using Nanoparticle‐Stabilized Nanocapsules

et al. 2014

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We report the use of nanoparticle-stabilized nanocapsules (NPSC) for the direct cytosolic delivery of siRNA. In this approach, siRNA is complexed with cationic arginine-functionalized gold nanoparticles via electrostatic interactions, with the resulting ensemble self-assembled onto the surface of fatty acid nanodroplets to form NPSC/siRNA nanocomplex. The complex rapidly delivers siRNA into cytosol via membrane fusion, a mechanism supported by cellular uptake studies. Using destabilized green fluorescent protein (deGFP) as a target, 90% knockdown was observed in HEK293 cells. Moreover, the delivery of siRNA targeting polo-like kinase 1(siPLK1) efficiently silenced PLK1 expression in cancer cells with concomitant cytotoxicity.

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“…Therefore, the ability of nanocarriers to escape from endosomes is also critical for effective intracellular delivery and improved efficacy of protein therapeutics 124 .…”

Section: Discussionmentioning

confidence: 99%

Redox-responsive nanocapsules for intracellular protein delivery

et al. 2011

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Proteins play a crucial role in life, taking part in all vital processes in the body. Intracellular protein delivery holds enormous promise for biological and medical applications, including cancer therapy, vaccination, regenerative medicine, treatment for loss-of-function genetic diseases and imaging. Engineering vehicles for escorting therapeutic proteins into specific cells in a controlled release fashion has thus generated considerable interest. The development of such therapeutics to selectively target tumor has also been a major research focus in cancer nanotechnology. A novel strategy using polymeric redox-responsive nanocapsules for intracellular protein delivery is described, in which through in situ interfacial polymerization, the target therapeutic protein is noncovalently encapsulated into a biocompatible polymeric shell interconnected by disulfide-containing crosslinkers. The dissociation of the polymeric shell under reducing conditions and the subsequent release of protein were confirmed using cell-free assays in the presence of glutathione. Several therapeutic proteins with different properties, both cytosolic and nuclear, were successfully delivered using the platform. The nanocapsules were demonstrated to be efficiently internalized into mammalian cells through interactions between charge or targeting ligand, iii and to release the protein in the reducing cytosol in active forms. Using such redoxresponsive nanocapsule as a vehicle, pro-apoptotic protein caspase 3 was delivered to induce apoptosis in a variety of human cancer cell lines, including HeLa, MCF-7 and U-87 MG.Tumor-selective killer apoptin was delivered into different breast cancer cell lines as well, which led to rapid resurrection of apoptosis in breast cancer cell lines and shrinkage of xenograft mice models. Tumor suppressor p53 protein, the most commonly mutated protein, was also delivered selectively into tumor cells for apoptosis induction, through targeted redox-responsive nanocapsules. The delivery methodology is general, effective and nontoxic towards healthy cells. This work facilitate the development of new tools for tumorgenesis and drug resistance studies, as well as expanding current therapeutic target pool to many other tumor suppressor proteins for cancer treatment.iv The Dissertation of Muxun Zhao is approved.

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Biomimetic Nanocarrier for Direct Cytosolic Drug Delivery

Cited by 150 publications

References 38 publications

Green design “bioinspired disassembly-reassembly strategy” applied for improved tumor-targeted anticancer drug delivery

Green design “bioinspired disassembly-reassembly strategy” applied for improved tumor-targeted anticancer drug delivery

Direct Cytosolic Delivery of siRNA Using Nanoparticle‐Stabilized Nanocapsules

Redox-responsive nanocapsules for intracellular protein delivery

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