Recent Advances in Chemical Biology of Mitochondria Targeting

Wang, Haiwei; Fang, Bin; Peng, Bo; Wang, Limin; Xue, Yufei; Bai, Hua; Lu, Shenci; Voelcker, Nicolas H.; Li, Lin; Fu, Li; Huang, Wei

doi:10.3389/fchem.2021.683220

Cited by 43 publications

(45 citation statements)

References 142 publications

(173 reference statements)

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“…Decades ago, a group of mitochondria-targeting small molecules were discovered for various biological applications by targeting the highly negative mitochondrial membrane potential. Although a few molecules (e.g., pyruvate [ 43 ] and glycyrrhetinic acid [ 44 ]) were reported for mitochondria-targeting, the most well-established mitochondria-targeting molecules were identified as delocalized lipophilic cations ( Figure 1 ), such as triphenylphosphonium (TPP)-based antioxidant mitoquinone mesylate (MitoQ), 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethyl-imidacarbocyanine (JC-1), and rhodamine 123 [ 45 , 46 , 47 ]. The lipid solubility of these molecules enables them to cross the cell membrane and mitochondrial membrane, and the positive charge enables them to enter MM under the action of the mitochondrial membrane potential, rendering them with mitochondria-targeting and accumulating ability.…”

Section: Fundamentals Of Mitochondria-targetingmentioning

confidence: 99%

“…TPP targets and penetrates the mitochondrial membranes in a multi-step process: it binds to the outer mitochondrial membrane (OMM), then moves to and crosses the inner mitochondrial membrane (IMM), and finally dissociates from IMM. The cationic structure naturally allows for electrostatic targeting and accumulation inside the mitochondrial matrix which has a highly negative membrane potential, compared to the cell membrane potential (−25 mV) [ 47 ]. Due to the highly specific and efficient mitochondria-targeting properties of lipophilic cations, such as TPP, the biological applications of such a simple and effective strategy for mitochondria-specific delivery are unlimited.…”

Section: Fundamentals Of Mitochondria-targetingmentioning

confidence: 99%

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Recent Advancements in Mitochondria-Targeted Nanoparticle Drug Delivery for Cancer Therapy

Shamul

Kwizera

et al. 2022

Nanomaterials

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Mitochondria are critical subcellular organelles that produce most of the adenosine triphosphate (ATP) as the energy source for most eukaryotic cells. Moreover, recent findings show that mitochondria are not only the “powerhouse” inside cells, but also excellent targets for inducing cell death via apoptosis that is mitochondria-centered. For several decades, cancer nanotherapeutics have been designed to specifically target mitochondria with several targeting moieties, and cause mitochondrial dysfunction via photodynamic, photothermal, or/and chemo therapies. These strategies have been shown to augment the killing of cancer cells in a tumor while reducing damage to its surrounding healthy tissues. Furthermore, mitochondria-targeting nanotechnologies have been demonstrated to be highly efficacious compared to non-mitochondria-targeting platforms both in vitro and in vivo for cancer therapies. Moreover, mitochondria-targeting nanotechnologies have been intelligently designed and tailored to the hypoxic and slightly acidic tumor microenvironment for improved cancer therapies. Collectively, mitochondria-targeting may be a promising strategy for the engineering of nanoparticles for drug delivery to combat cancer.

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Section: Fundamentals Of Mitochondria-targetingmentioning

confidence: 99%

Section: Fundamentals Of Mitochondria-targetingmentioning

confidence: 99%

Recent Advancements in Mitochondria-Targeted Nanoparticle Drug Delivery for Cancer Therapy

Shamul

Kwizera

et al. 2022

Nanomaterials

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“…Many natural and artificial short peptides and polypeptides have mitochondrial targeting ability [235,236]. Typically, these peptides comprise hydrophobic (phenylalanine, tyrosine, isoleucine) and positively charged (D-arginine, lysine) amino acids.…”

Section: Mitochondrial Deliverymentioning

confidence: 99%

“…In addition to MTSs that are recognized by translocators, several smaller peptides consisting of 4-16 cationic and hydrophobic residues efficiently target and permeate mitochondrial double membranes [235,237]. These mitochondria-penetrating peptides (MPPs), also known as mitochondrial CPPs (mtCPPs), typically appear to penetrate cellular membranes directly rather than by endocytosis [238].…”

Section: Mitochondrial Deliverymentioning

confidence: 99%

Peptide-Assisted Nucleic Acid Delivery Systems on the Rise

Tarvirdipour

Skowicki

Schoenenberger

et al. 2021

IJMS

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Concerns associated with nanocarriers’ therapeutic efficacy and side effects have led to the development of strategies to advance them into targeted and responsive delivery systems. Owing to their bioactivity and biocompatibility, peptides play a key role in these strategies and, thus, have been extensively studied in nanomedicine. Peptide-based nanocarriers, in particular, have burgeoned with advances in purely peptidic structures and in combinations of peptides, both native and modified, with polymers, lipids, and inorganic nanoparticles. In this review, we summarize advances on peptides promoting gene delivery systems. The efficacy of nucleic acid therapies largely depends on cell internalization and the delivery to subcellular organelles. Hence, the review focuses on nanocarriers where peptides are pivotal in ferrying nucleic acids to their site of action, with a special emphasis on peptides that assist anionic, water-soluble nucleic acids in crossing the membrane barriers they encounter on their way to efficient function. In a second part, we address how peptides advance nanoassembly delivery tools, such that they navigate delivery barriers and release their nucleic acid cargo at specific sites in a controlled fashion.

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“…The prodrug is obtained by directly coupling the drug and the carrier through chemical bonds, which can accurately control the drug loading and increase the solubility and stability of the drug (Deng et al, 2021;Du et al, 2021;Yang et al, 2021). It thus changes the biodistribution, improves pharmacokinetics and pharmacodynamics, increases therapeutic effect, and reduces side effect (Dhiman et al, 2021;Wang et al, 2021). FDAapproved polymers such as PLGA, PEG, and dextran have been widely used in the development of polymer-drug conjugates (prodrugs) (Li et al, 2017;Hong et al, 2020;Zeng et al, 2020;An et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

A Co-delivery System Based on a Dimeric Prodrug and Star-Shaped Polymeric Prodrug Micelles for Drug Delivery

et al. 2021

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Chemotherapy is one of the commonly used therapies for the treatment of malignant tumors. Insufficient drug-loading capacity is the major challenge for polymeric micelle–based drug delivery systems of chemotherapy. Here, the redox-responsive star-shaped polymeric prodrug (PSSP) and the dimeric prodrug of paclitaxel (PTX) were prepared. Then the dimeric prodrug of PTX (diPTX, diP) was loaded into the core of the star-shaped polymeric prodrug micelles of PSSP by hydrophobic interaction forming the redox-responsive prodrug micelles of diPTX@PSSP for intracellular drug release in tumor cells. The hydrodynamic diameter of diPTX@PSSP nanoparticles was 114.3 nm ± 2.1 (PDI = 0.219 ± 0.016), and the micelles had long-term colloidal stability and the drug-loading content (DLC) of diPTX and PTX is 16.7 and 46.9%, respectively. The prepared micelles could broke under the reductive microenvironment within tumor cells, as a result, the dimeric prodrug of diP and polymeric prodrug micelles of PSSP were rapidly disassembled, leading to the rapid release of intracellular drugs. In vitro release studies showed that under the condition of reduced glutathione (GSH) (10 mM), the release of PTX was significantly accelerated with approximately 86.6% released within 21 h, and the released PTX in cytoplasm could promote the disintegration of microtubules and induce cell apoptosis. These results indicated that the new type of this reduction-sensitive nanodrug delivery system based on dimeric prodrug@polymeric prodrug micelles would be a promising technology in chemotherapy.

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Recent Advances in Chemical Biology of Mitochondria Targeting

Cited by 43 publications

References 142 publications

Recent Advancements in Mitochondria-Targeted Nanoparticle Drug Delivery for Cancer Therapy

Recent Advancements in Mitochondria-Targeted Nanoparticle Drug Delivery for Cancer Therapy

Peptide-Assisted Nucleic Acid Delivery Systems on the Rise

A Co-delivery System Based on a Dimeric Prodrug and Star-Shaped Polymeric Prodrug Micelles for Drug Delivery

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