DNA delivery to the mitochondria sites using mitochondrial leader peptide conjugated polyethylenimine

Lee, Minhyung; Choi, Ji Soo; Choi, Min Ji; Pak, Youngmi Kim; Rhee, Byoung Doo; Ko, Kyung Soo

doi:10.1080/10611860600953555

Cited by 31 publications

(8 citation statements)

References 41 publications

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“…422 Lee et al . 422 conjugated the mitochondrial leader peptide to PEI NPs by means of a disulfide bond and confirmed the complex formation of PEI–MLP with DNA by a gel retardation assay. In vitro delivery tests of rhodamine-labelled DNA into living cells demonstrated that PEI–MLP/DNA complexes were localized at mitochondrial sites.…”

Section: Novel Trends In the Development Of Targeted Polymeric Nanmentioning

confidence: 99%

Targeted polymeric therapeutic nanoparticles: design, development and clinical translation

et al. 2012

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Polymeric materials have been used in a range of pharmaceutical and biotechnology products for more than 40 years. These materials have evolved from their earlier use as biodegradable products such as resorbable sutures, orthopaedic implants, macroscale and microscale drug delivery systems such as microparticles and wafers used as controlled drug release depots, to multifunctional nanoparticles (NPs) capable of targeting, and controlled release of therapeutic and diagnostic agents. These newer generations of targeted and controlled release polymeric NPs are now engineered to navigate the complex in vivo environment, and incorporate functionalities for achieving target specificity, control of drug concentration and exposure kinetics at the tissue, cell, and subcellular levels. Indeed this optimization of drug pharmacology as aided by careful design of multifunctional NPs can lead to improved drug safety and efficacy, and may be complimentary to drug enhancements that are traditionally achieved by medicinal chemistry. In this regard, polymeric NPs have the potential to result in a highly differentiated new class of therapeutics, distinct from the original active drugs used in their composition, and distinct from first generation NPs that largely facilitated drug formulation. A greater flexibility in the design of drug molecules themselves may also be facilitated following their incorporation into NPs, as drug properties (solubility, metabolism, plasma binding, biodistribution, target tissue accumulation) will no longer be constrained to the same extent by drug chemical composition, but also become in-part the function of the physicochemical properties of the NP. The combination of optimally designed drugs with optimally engineered polymeric NPs opens up the possibility of improved clinical outcomes that may not be achievable with the administration of drugs in their conventional form. In this critical review, we aim to provide insights into the design and development of targeted polymeric NPs and to highlight the challenges associated with the engineering of this novel class of therapeutics, including considerations of NP design optimization, development and biophysicochemical properties. Additionally, we highlight some recent examples from the literature, which demonstrate current trends and novel concepts in both the design and utility of targeted polymeric NPs (444 references).

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Section: Novel Trends In the Development Of Targeted Polymeric Nanmentioning

confidence: 99%

Targeted polymeric therapeutic nanoparticles: design, development and clinical translation

et al. 2012

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“…Such complexes were reported to be imported into isolated mammalian mitochondria and into the mitochondria of permeabilized cultured mammalian cells. In a similar design, the mitochondrial-targeting peptide was conjugated to a polyethylenimine moiety that carried the DNA (Lee et al 2007;Fig. 13.4).…”

Section: Further Conjugatesmentioning

confidence: 99%

Mitochondrial Genetic Manipulation

Mileshina

Niazi

Weber-Lotfi

et al. 2015

Somatic Genome Manipulation

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“…42,[46][47][48][49][50] Additionally, polyethyleneimine has been successfully 'tagged' with peptides to further enhance transfection efficiency and to facilitate targeted delivery. [51][52][53][54][55] Also, an experimental layer-by-layer electrostatic approach has been used to overcome aggregation issues 42 . We therefore postulated that the use of polyethyleneimine-coated GNP may overcome the barrier to successful delivery of RNA to the cytoplasm of hard-to-transfect lymphocytes.…”

Section: Polyethyleneimine To Enhance Cell Entry and Facilitate Endosmentioning

confidence: 99%

Synthesis, Characterization and Biocompatibility of a Multifunctional Gold Nanoparticle System for the Delivery of Single-Stranded RNA to Lymphocytes

et al. 2018

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The use of RNA macromolecules as therapeutic agents for HIV and other infectious diseases is promising but limited by suboptimal delivery to the target site. With HIV infection, this is particularly challenging since lymphocytes are particularly difficult to transfect. This paper describes an innovative strategy for the intracellular delivery of a novel single-stranded RNA (oligoribonucleotide) with putative anti-HIV activity. This strategy is based on a PEGylated gold nanoparticle scaffold covalently linked to the thiol-modified oligoribonucleotide via a cleavable N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP) linker molecule. The nanoparticle was then coated with a cationic polymer (polyethyleneimine) to facilitate cell entry and endosomal escape. A synthetic anti-CD4 cyclic targeting peptide was attached to the polyethyleneimine-coated nanoparticle via an SPDP linker molecule, in an attempt to enhance uptake and selectivity. Synthesis, characterization, SPDP and RNA loading, cytotoxicity and antiviral activity of the nanoparticle are described. Approximately 45 000 strands of RNA were taken up per lymphocyte. Uptake was limited by relatively inefficient loading of RNA onto the gold nanoparticle surface (1 strand per 4.8 nm 2 of nanoparticle surface area) and significant aggregation of the nanoparticle in physiological solutions. No antiviral activity was demonstrated, possibly due to insufficient intracytoplasmic delivery of the RNA.

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DNA delivery to the mitochondria sites using mitochondrial leader peptide conjugated polyethylenimine

Cited by 31 publications

References 41 publications

Targeted polymeric therapeutic nanoparticles: design, development and clinical translation

Targeted polymeric therapeutic nanoparticles: design, development and clinical translation

Mitochondrial Genetic Manipulation

Synthesis, Characterization and Biocompatibility of a Multifunctional Gold Nanoparticle System for the Delivery of Single-Stranded RNA to Lymphocytes

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