Enhanced Subcellular Trafficking of Resveratrol Using Mitochondriotropic Liposomes in Cancer Cells

Kang, Ji Hee; Ko, Young Tag

doi:10.3390/pharmaceutics11080423

Cited by 43 publications

(24 citation statements)

References 53 publications

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“…The enhanced uptake was also demonstrated by LCMS/MS quantified resveratrol in the subcellular organelles. The mitochondrial membrane dissipation, ROS production, and cell cytotoxicity results demonstrated that these liposomes can provide a vital subcellular targeting strategy in the cancer treatment (Kang and Ko, 2019).…”

Section: Current Scenario Of Subcellular Drug Targetingmentioning

confidence: 99%

Membrane Trafficking and Subcellular Drug Targeting Pathways

Kumar¹,

Ahmad²,

Vyawahare³

et al. 2020

Front. Pharmacol.

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The movement of micro and macro molecules into and within a cell significantly governs several of their pharmacokinetic and pharmacodynamic parameters, thus regulating the cellular response to exogenous and endogenous stimuli. Trafficking of various pharmacological agents and other bioactive molecules throughout and within the cell is necessary for the fidelity of the cells but has been poorly investigated. Novel strategies against cancer and microbial infections need a deeper understanding of membrane as well as subcellular trafficking pathways and essentially regulate several aspects of the initiation and spread of anti-microbial and anti-cancer drug resistance. Furthermore, in order to avail the maximum possible bioavailability and therapeutic efficacy and to restrict the unwanted toxicity of pharmacological bioactives, these sometimes need to be functionalized with targeting ligands to regulate the subcellular trafficking and to enhance the localization. In the recent past the scenario drug targeting has primarily focused on targeting tissue components and cell vicinities, however, it is the membranous and subcellular trafficking system that directs the molecules to plausible locations. The effectiveness of the delivery platforms largely depends on their physicochemical nature, intracellular barriers, and biodistribution of the drugs, pharmacokinetics and pharmacodynamic paradigms. Most subcellular organelles possess some peculiar characteristics by which membranous and subcellular targeting can be manipulated, such as negative transmembrane potential in mitochondria, intraluminal delta pH in a lysosome, and many others. Many specialized methods, which positively promote the subcellular targeting and restrict the off-targeting of the bioactive molecules, exist. Recent advancements in designing the carrier molecules enable the handling of membrane trafficking to facilitate the delivery of active compounds to subcellular localizations. This review aims to cover membrane trafficking pathways which promote the delivery of the active molecule in to the subcellular locations, the associated pathways of the subcellular drug delivery system, and the role of the carrier system in drug delivery techniques.

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Section: Current Scenario Of Subcellular Drug Targetingmentioning

confidence: 99%

Membrane Trafficking and Subcellular Drug Targeting Pathways

Kumar¹,

Ahmad²,

Vyawahare³

et al. 2020

Front. Pharmacol.

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“…Recently, it was demonstrated that TPP, as part of the vectors, can transfer chemotherapeutic drugs into cancer cells and simultaneously target mitochondria in cancer cells [25]. In this study, F127 was conjugated to COOH-TPP by esterification using DCC/DMAP.…”

Section: Synthesis and Characterization Of Tph/ptxmentioning

confidence: 99%

“…Twenty tumor-bearing mice (A549/ADR) were used when the volume of the tumors reached approximately 220-230 mm 3 . The animals were randomly divided into four groups, namely, groups treated with saline, Taxol, TP/PTX, and TPH/PTX nanomicelles (n = 5), and treated at days 17,19,21,23,25,27, and 29 via the tail vein. The final concentration of PTX was 10 mg/kg.…”

Section: Antitumor Efficacy In Vivomentioning

confidence: 99%

Tumor- and mitochondria-targeted nanoparticles eradicate drug resistant lung cancer through mitochondrial pathway of apoptosis

et al. 2020

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Chemotherapeutic drugs frequently encounter multidrug resistance. ATP from mitochondria helps overexpression of drug efflux pumps to induce multidrug resistance, so mitochondrial delivery as a means of "repurposing'' chemotherapeutic drugs currently used in the clinic appears to be a worthwhile strategy to pursue for the development of new anti-drug-resistant cancer agents. TPP-Pluronic F127-hyaluronic acid (HA) (TPH), with a mitochondria-targeting triphenylphosphine (TPP) head group, was first synthesized through ester bond formation. Paclitaxel (PTX)-loaded TPH (TPH/PTX) nanomicelles exhibited excellent physical properties and significantly inhibited A549/ADR cells. After TPH/ PTX nanomicelles entered acidic lysosomes through macropinocytosis, the positively charged TP/PTX nanomicelles that resulted from degradation of HA by hyaluronidase (HAase) in acidic lysosomes were exposed and completed lysosomal escape at 12 h, finally localizing to mitochondria over a period of 24 h in A549/ADR cells. Subsequently, TPH/PTX caused mitochondrial outer membrane permeabilization (MOMP) by inhibiting antiapoptotic Bcl-2, leading to cytochrome C release and activation of caspase-3 and caspase-9. In an A549/ADR xenograft tumor model and a drug-resistant breast cancer-bearing mouse model with lung metastasis, TPH/PTX nanomicelles exhibited obvious tumor targeting and significant antitumor efficacy. This work presents the potential of a single, nontoxic nanoparticle (NP) platform for mitochondria-targeted delivery of therapeutics for diverse drug-resistant cancers.

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“…Resveratrol-loaded nanocarriers effectively deliver resveratrol into mitochondria of cancer cells. Resveratrol promotes the generation of ROS to depolarize the mitochondrial membrane resulting in apoptotic cell death [221]. Loading resveratrol on the mitochondrial-targeted titanium disulfide nanosheets is another potential strategy in cancer chemotherapy.…”

Section: Selective Targeting Of Mitochondria In Cancer Therapy Using mentioning

confidence: 99%

Natural products and phytochemical nanoformulations targeting mitochondria in oncotherapy: an updated review on resveratrol

et al. 2020

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Mitochondria are intracellular organelles with two distinct membranes, known as an outer mitochondrial membrane and inner cell membrane. Originally, mitochondria have been derived from bacteria. The main function of mitochondria is the production of ATP. However, this important organelle indirectly protects cells by consuming oxygen in the route of energy generation. It has been found that mitochondria are actively involved in the induction of the intrinsic pathways of apoptosis. So, there have been efforts to sustain mitochondrial homeostasis and inhibit its dysfunction. Notably, due to the potential role of mitochondria in the stimulation of apoptosis, this organelle is a promising target in cancer therapy. Resveratrol is a non-flavonoid polyphenol that exhibits significant pharmacological effects such as antioxidant, anti-diabetic, anti-inflammatory and anti-tumor. The anti-tumor activity of resveratrol may be a consequence of its effect on mitochondria. Multiple studies have investigated the relationship between resveratrol and mitochondria, and it has been demonstrated that resveratrol is able to significantly enhance the concentration of reactive oxygen species, leading to the mitochondrial dysfunction and consequently, apoptosis induction. A number of signaling pathways such as sirtuin and NF-κB may contribute to the mitochondrial-mediated apoptosis by resveratrol. Besides, resveratrol shifts cellular metabolism from glycolysis into mitochondrial respiration to induce cellular death in cancer cells. In the present review, we discuss the possible interactions between resveratrol and mitochondria, and its potential application in cancer therapy.

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Enhanced Subcellular Trafficking of Resveratrol Using Mitochondriotropic Liposomes in Cancer Cells

Cited by 43 publications

References 53 publications

Membrane Trafficking and Subcellular Drug Targeting Pathways

Membrane Trafficking and Subcellular Drug Targeting Pathways

Tumor- and mitochondria-targeted nanoparticles eradicate drug resistant lung cancer through mitochondrial pathway of apoptosis

Natural products and phytochemical nanoformulations targeting mitochondria in oncotherapy: an updated review on resveratrol

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