Mitochondria Targeting Drug Delivery Systems

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmaceutical Technology".

Deadline for manuscript submissions: closed (15 October 2022) | Viewed by 4081

Special Issue Editor

Institute of Nanoscience and Nanotechnology, National Centre for Scientific Research “Demokritos”, P.O. Box 60037, 15310 Aghia Paraskevi, Attiki, Greece
Interests: functional liposomes; functional dendritic polymers; nano-sized drug delivery systems; drug targeting; triggered drug release
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Special Issue Information

Dear Colleagues,

Cell mitochondria are much more than the power stations generating ATP, which is then distributed to meet the energy requirements of cell functions. Apart from the nucleus, they are the only subcellular organelles containing their own genome, and the related mitochondrial proteome is of crucial importance to cell functions. Furthermore, mitochondria are the main source of intracellular reactive oxygen species (ROS) that play crucial roles in cell signalling and homeostasis, and have also been found to control the response to cell death signals. Thus, both mitochondrial DNA (mtDNA) mutations and mitochondrial dysfunctions are associated with several pathologies, including neurodegenerative and neuromuscular diseases, obesity, diabetes, and cancer. This led to the emergence of the so-called mitochondrial medicine for treating mitochondria dysfunctions and, complementary to this, to the need for specific and efficient delivery of therapeutic agents and/or imaging agents to mitochondria. A number of mitotropic agents that can target mitochondria have been identified, from delocalized lipophilic cations to mitochondria-penetrating peptides. Mitochondrial targeting has so-far been pursued by either direct conjugation of bioactive molecules, or imaging groups, with these mitotropic agents, or with mitotropic functionalization of drug-loaded delivery systems, such as complexes, emulsions, polymers, liposomes and lipid nanoparticles, inorganic nanoparticles, nanocarbons, etc. The field is relative new and further research is needed, as these systems, before reaching mitochondria, must evade the immune system, access specific tissues/organs, and finally have the ability to translocate through cell and mitochondrial membranes. This Special Issue invites both mini-review and review articles to summarize the current knowledge, and original research articles to advance our knowledge on both novel mitotropic agents and mitochondriotropic drug delivery systems aiming to increase scientific interest on this promising, but not yet clinically proven, area of research.

Dr. Dimitris Tsiourvas
Guest Editor

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Keywords

  • mitochondria dysfunctions
  • mitotropic agents
  • mitochondrial membrane potential
  • controlled release
  • triggered release
  • bioimaging
  • pharmacokinetics
  • biodistribution

Published Papers (2 papers)

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Research

19 pages, 5718 KiB  
Article
The Anti-Cancer Effects of Mitochondrial-Targeted Triphenylphosphonium–Resveratrol Conjugate on Breast Cancer Cells
Pharmaceuticals 2022, 15(10), 1271; https://doi.org/10.3390/ph15101271 - 15 Oct 2022
Cited by 2 | Viewed by 1729
Abstract
Breast cancer is the most commonly diagnosed cancer in women. Resveratrol, a naturally occurring phytochemical, shows great promise in developing novel anti-cancer therapies. This study hypothesized that the mitochondria-targeted delivery of resveratrol would increase its potency and induce mitochondria-mediated apoptosis. The targeted delivery [...] Read more.
Breast cancer is the most commonly diagnosed cancer in women. Resveratrol, a naturally occurring phytochemical, shows great promise in developing novel anti-cancer therapies. This study hypothesized that the mitochondria-targeted delivery of resveratrol would increase its potency and induce mitochondria-mediated apoptosis. The targeted delivery of resveratrol was achieved by conjugating resveratrol to triphenylphosphonium (TPP). The anti-cancer effects of TPP-resveratrol were studied in the murine breast cancer 4T1 and the human breast cancer MDA-MB-231 cell lines. Flow cytometry was used to study apoptosis induction, cell cycle arrest, and mitochondrial membrane potential loss. The morphological changes in the mitochondria in MDA-MB-231 cells after TPP-resveratrol treatments were examined using transmission electron microscopy. Moreover, the changes in MDA-MB-231 cell metabolism after resveratrol and TPP-resveratrol treatments were studied using metabolomic analysis. We demonstrate that TPP-resveratrol significantly improved cytotoxicity in 4T1 cells and MDA-MB-231 cells by inducing apoptosis and mitochondrial membrane potential loss. Swollen and vacuolated mitochondria were observed after the TPP-resveratrol treatment. Meanwhile, TPP-resveratrol treatment down-regulated amino acid and energy metabolism and caused the dysfunction of purine and pyrimidine metabolism. Our results provide evidence supporting the targeted delivery of resveratrol to mitochondria and suggest that TPP-resveratrol may be an effective agent for breast cancer treatment. Full article
(This article belongs to the Special Issue Mitochondria Targeting Drug Delivery Systems)
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