Exocytosis - a putative road-block in nanoparticle and nanocomplex mediated gene delivery

Dahiya, Ujjwal Ranjan; Ganguli, Munia

doi:10.1016/j.jconrel.2019.04.012

Cited by 35 publications

(27 citation statements)

References 86 publications

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“…A few studies have demonstrated endocytic recycling of ASOs, as well as nanocarriers via fast recycling, lysosomal, or multivesicular-body-mediated pathways. 20,21 In this study, we investigated the endocytic recycling of a class of SS ASOs known as peptide nucleic acids (PNAs). PNAs are synthetic DNA mimics in which the phosphodiester backbone is replaced by a pseudo-peptide backbone of N-(2-aminoethyl) glycine units and purine or pyrimidine nucleobases are attached via a methyl carbonyl linker.…”

Section: Introductionmentioning

confidence: 99%

Extracellular vesicles mediated exocytosis of antisense peptide nucleic acids

Malik

Saltzman

Bahal

2021

Molecular Therapy - Nucleic Acids

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Peptide nucleic acids (PNAs), a synthetic DNA mimic, have been extensively utilized for antisense-and antigene-based biomedical applications. Significant efforts have been made to increase the cellular uptake of PNAs, but here we examined relatively unexplored aspects of intracellular trafficking and endocytic recycling of PNAs. For proof-of-concept, we used anti-microRNA (miR) PNA targeting miR-155. The sub-cellular localization of PNA was studied via confocal and flow-cytometry-based assays in HeLa cells. A comprehensive characterization of PNA-containing extracellular vesicles revealed spherical morphology, negative surface charge density, and the presence of tetraspanin markers. Most importantly, we investigated rab11a and rab27b GTPases' role in regulating the exocytosis of PNAs. Organelle staining, followed by confocal imaging, showed higher localization of PNA in lysosomes. Gene-expression analysis established the enhanced functional activity of PNA after inhibition of endocytic recycling. Multiple studies report the exocytosis of single-stranded oligonucleotides, short interfering RNAs (siRNAs), and nanocarriers. To our knowledge, this is the first mechanistic study to establish that PNA undergoes endocytic recycling and exocytosis out of tumor cells. The results presented here can serve as a platform to develop and optimize strategies for improving the therapeutic efficacy of PNAs by avoiding the recycling pathways.

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Section: Introductionmentioning

confidence: 99%

Extracellular vesicles mediated exocytosis of antisense peptide nucleic acids

Malik

Saltzman

Bahal

2021

Molecular Therapy - Nucleic Acids

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“…There is the exquisite complexity involved also in the absorption of nanoparticles by the oral route due to the dimensionally constraining and moving intestinal villi and microvilli and through their actin substructures. There are, too, the general issues of particokinetics [ 7 ] and three processes in target cell uptake: (i) endocytosis, (ii) diffusion of particles through cells and (iii) the potential “road block” of exocytosis [ 8 ]. All are of vital importance in reaching the exact narrative of nanoparticle delivery that we must embrace, critique and consider so that new approaches can be developed to surmount these difficulties.…”

Section: Obstructionsmentioning

confidence: 99%

Trajectories in nanotechnology: embracing complexity, seeking analogies

Florence

2021

Drug Deliv. and Transl. Res.

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This account comprises personal reflections on the field of nanosystems primarily designed for the delivery of biologically active agents. It emphasises the colloidal nature of nanoparticles obeying the same physical laws that dictate the behaviour of disperse systems. Research reveals not only intrinsic complexities but a variety of possible trajectories in vivo and ex vivo, issues of stability, interactions and behaviour in a range of often constrained environments. Such are the variations in the chemical and physical nature of the nanosystems and the active agents they carry, their putative “targets” and the many biological systems and models in which they are employed, it is not possible to generalise. Stochastic events may exclude precise prediction or extrapolation of outcomes, but embracing and studying complexity lead to new insights, often aided by consideration of analogies in cognate areas. This is part of the process of illumination. Unexpected results provide the true essence and excitement of scientific endeavour. Simplification is perhaps its antithesis.

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“…A recent review discusses the impact of cellular retention versus exocytosis of nanomaterial platforms on their efficacy. [111] The Reproduced with permission. [97] Copyright 2016, American Chemical Society.…”

Section: Targeting Epithelial Transport Pathwaysmentioning

confidence: 99%

“…A recent review discusses the impact of cellular retention versus exocytosis of nanomaterial platforms on their efficacy. [111] The Adv. Funct.…”

Section: Targeting Epithelial Transport Pathwaysmentioning

confidence: 99%

Biomaterial Approaches for Understanding and Overcoming Immunological Barriers to Effective Oral Vaccinations

Frizzell

Woodrow

2020

Adv Funct Materials

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Oral vaccines have the potential to reduce cost, improve compliance, and induce immunity at mucosal surfaces that are the first line of defense against infection. The gastrointestinal tract is highly evolved to efficiently digest and absorb nutrients without eliciting aberrant inflammation. However, these functions also limit the efficacy of immunization by the oral route. While mechanisms responsible for the development of tolerance to fed antigens are being illuminated, the application of materials with precise physiochemical properties and immunomodulatory potential may accelerate understanding of immunity within the gastrointestinal tract. Insight into these immunological mechanisms can inform the design of next‐generation oral vaccines to harness critical functions to elicit immunity. Here, material strategies for oral vaccines and their dual function in understanding and overcoming immunological barriers associated with oral immunization are discussed.

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Exocytosis - a putative road-block in nanoparticle and nanocomplex mediated gene delivery

Cited by 35 publications

References 86 publications

Extracellular vesicles mediated exocytosis of antisense peptide nucleic acids

Extracellular vesicles mediated exocytosis of antisense peptide nucleic acids

Trajectories in nanotechnology: embracing complexity, seeking analogies

Biomaterial Approaches for Understanding and Overcoming Immunological Barriers to Effective Oral Vaccinations

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