DQAsome-mediated delivery of plasmid DNA toward mitochondria in living cells

D’Souza, Gerard G. M.; Rammohan, Ram; Cheng, Shing‐Ming; Torchilin, Vladimir P.; Weissig, Volkmar

doi:10.1016/s0168-3659(03)00297-9

Cited by 187 publications

(115 citation statements)

References 16 publications

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“…Those vesicles could escape the endosomes, localize at the mitochondrial membrane, and release the pDNA in close proximity of the targeted organelle. [161] DQA was also conjugated to PEG chains for the decoration of liposomes. This allowed endosomal escape and subsequent mitochondrial targeting.…”

Section: Mitochondrial Deliverymentioning

confidence: 99%

Controlling and Monitoring Intracellular Delivery of Anticancer Polymer Nanomedicines

Battistella

Klok

2017

Macromolecular Bioscience

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Polymer nanomedicines are very attractive to improve the delivery of chemotherapeutics. Polymer conjugates and other polymer‐based nanocarriers allow to increase plasma half‐life and drug bioavailability and can also be guided toward tumors using passive and active targeting strategies. Since many chemotherapeutics act on targets that are located in well‐defined subcellular compartments, other important factors that contribute to an efficient therapy include cellular internalization and subsequent intracellular trafficking of the polymer nanomedicines and/or its payload to the appropriate organelle in the cytoplasm. This article provides an overview of the different approaches that have been developed to control intracellular delivery of polymer nanomedicines and discusses the different techniques that can be used to monitor these processes.

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Section: Mitochondrial Deliverymentioning

confidence: 99%

Controlling and Monitoring Intracellular Delivery of Anticancer Polymer Nanomedicines

Battistella

Klok

2017

Macromolecular Bioscience

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“…Weissig and co-workers attempted to deliver pDNA to mitochondria using DQAsomes, which are mitochondriotropic and cationic 'bola-lipid'-based vesicles , D'Souza et al, 2003 (Fig. 1 D).…”

Section: Strategy For Dna Delivery Using Mitochondriotropic Lipoplexmentioning

confidence: 99%

“…14 they demonstrated that DQAplexes appear to be able to escape from endosomes without losing their pDNA, and specifically release pDNA at the proximal region of mitochondria (D'Souza et al, 2003). More recently, they tried to deliver pDNA into mitochondrial matrix by means of a more optimized system based on their carrier (D'Souza et al, 2005).…”

Section: Yamada Y Et Almentioning

confidence: 99%

Mitochondrial drug delivery and mitochondrial disease therapy – An approach to liposome-based delivery targeted to mitochondria

et al. 2007

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Recent progress in genetics and molecular biology has provided useful information regarding the molecular mechanisms associated with the mitochondrial diseases. Genetic approaches were initiated in the late 1980s to clarify the gene responsible for various mitochondrial diseases, and information concerning genetic mutations is currently used in the diagnosis of mitochondrial diseases. Moreover, it was also revealed that mitochondria play a central role in apoptosis, or programmed cell death, which is closely related to the loss of physiological functions of tissues. Therefore, drug therapies targeted to the mitochondria would be highly desirable. In spite of the huge amount of mechanism-based studies of mitochondrial diseases, effective therapies have not yet been established mainly because of the lack of an adequate delivery system. To date, numerous investigators have attempted to establish a mitochondrial drug delivery system. However, many problems remain to be overcome before a clinical application can be achieved. To fulfill a drug delivery targeted to mitochondria, we first need to establish a method to encapsulate various drugs, proteins, peptides, and genes into a drug carrier depending on their physical characteristics. Second, we need to target it to a specific cell. Finally, multi-processes of intracellular trafficking should be sophisticatedly regulated so as to release a drug carrier from the endosome to the cytosol, and thereafter to deliver to the mitochondria. In this review, we describe the current state of the development of mitochondrial drug delivery systems, and discuss the advantage and disadvantage of each system. Our current efforts to develop an efficient method for the packaging of macromolecules and regulating intracellular trafficking are also summarized.Furthermore, novel concept of "Regulation of intramitochondrial trafficking" is proposed herein as a future challenge to the development of a mitochondrial drug delivery system. Yamada, Y., et al 3 Keywords:Mitochondrial drug delivery; Mitochondrial protein therapy; Mitochondrial gene therapy; Transferrin and GALA system; multifunctional envelope-type nano device (MEND);Regulation of intramitochondrial trafficking. Yamada, Y., et al 4

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“…However, reports of mitochondrial genome targeting by means of an artificial gene vector are limited, although endogenous mitochondrial importing signal RNA can deliver exogenous RNA to mitochondria in mammalian cells [14,15]. Weissig and coworkers reported on the development of DQAsomes, which are mitochondriotropic and cationic vesicles designed for mitochondrial-targeted DNA delivery [16,17]. They showed that DQAsomes specifically release pDNA proximal to mitochondria in living cells [17,18], although the delivery of cargoes into the interior of mitochondria has not been validated.…”

Section: Introductionmentioning

confidence: 99%

“…Weissig and coworkers reported on the development of DQAsomes, which are mitochondriotropic and cationic vesicles designed for mitochondrial-targeted DNA delivery [16,17]. They showed that DQAsomes specifically release pDNA proximal to mitochondria in living cells [17,18], although the delivery of cargoes into the interior of mitochondria has not been validated.…”

Section: Introductionmentioning

confidence: 99%

Delivery of bioactive molecules to the mitochondrial genome using a membrane-fusing, liposome-based carrier, DF-MITO-Porter

Yamada

Harashima

2012

Biomaterials

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Mitochondrial dysfunction has been implicated in a variety of human diseases. It is now well accepted that mutations and defects in the mitochondrial genome form the basis of these diseases. Therefore, mitochondrial gene therapy and diagnosis would be expected to have great medical benefits. To achieve such an innovative a strategy, it will be necessary to deliver therapeutic agents into mitochondria in living cells. We report here on a novel an approach to accomplish this via the use of a Dual Function (DF)-MITO-Porter, aimed at the mitochondrial genome, so-called mitochondrial DNA (mtDNA). The DF-MITO-Porter, an innovative a nano carrier for mitochondrial delivery, has the ability to penetrate the endosomal and mitochondrial membranes via step-wise membrane fusion. We first constructed a DF-MITO-Porter encapsulating DNase I protein as a bioactive cargo. It was expected that mtDNA would be digested, when the DNase I was delivered to the mitochondria.We observed the intracellular trafficking of the carriers, and then measured mitochondrial activity and mtDNA-levels after the delivery of DNase I by the DF-MITO-Porter. The findings confirm that the DF-MITO-Porter effectively delivered the DNase I into the mitochondria, and provides a demonstration of its potential use in therapies that are selective for the mitochondrial genome. 3

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DQAsome-mediated delivery of plasmid DNA toward mitochondria in living cells

Cited by 187 publications

References 16 publications

Controlling and Monitoring Intracellular Delivery of Anticancer Polymer Nanomedicines

Controlling and Monitoring Intracellular Delivery of Anticancer Polymer Nanomedicines

Mitochondrial drug delivery and mitochondrial disease therapy – An approach to liposome-based delivery targeted to mitochondria

Delivery of bioactive molecules to the mitochondrial genome using a membrane-fusing, liposome-based carrier, DF-MITO-Porter

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