Enhanced Subcellular Trafficking of Resveratrol Using Mitochondriotropic Liposomes in Cancer Cells

Ji Hee Kang1, Young Tag Ko2

  • 1College of Pharmacy and Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon 21936, Korea.

Pharmaceutics
|August 23, 2019
PubMed

Insights

Novel mitochondria-targeting liposomes loaded with resveratrol demonstrate enhanced cancer cell death. These liposomes, TLS (Res) and DLS (Res), selectively accumulate in mitochondria, generating reactive oxygen species and disrupting membrane potential for effective cancer therapy.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Biology

Background:

  • Mitochondria are crucial organelles and a key target for cancer therapy.
  • Mitochondria-targeting strategies can overcome multi-drug resistance (MDR) in cancer cells.
  • Resveratrol exhibits anti-cancer properties but requires effective delivery.

Purpose of the Study:

  • To synthesize mitochondriotropic liposomes for targeted delivery of resveratrol.
  • To evaluate the efficacy of these liposomes in inducing cancer cell death via mitochondrial pathways.
  • To assess the potential of these liposomes in overcoming MDR mechanisms.

Main Methods:

  • Synthesis of TPP-DSPE-PEG and DQA-DSPE-PEG for mitochondriotropic liposomes.
  • Construction of resveratrol-loaded liposomes (TLS (Res) and DLS (Res)) with enhanced permeability and retention (EPR).
  • Confocal microscopy and LC-MS/MS to confirm cellular uptake and mitochondrial accumulation.

Main Results:

  • TLS (Res) and DLS (Res) liposomes exhibited ~120 nm size and positive zeta potential.
  • Demonstrated enhanced cellular uptake and selective mitochondrial accumulation of resveratrol.
  • Induced cancer cell cytotoxicity by generating reactive oxygen species (ROS) and dissipating mitochondrial membrane potential.

Conclusions:

  • Mitochondria-targeting liposomes (TLS (Res) and DLS (Res)) are effective for delivering resveratrol.
  • These liposomes offer a promising strategy for cancer treatment through mitochondrial targeting.
  • The approach stimulates mitochondrial signaling pathways for therapeutic benefit.

Related Concept Videos

Subcellular Fractionation01:32

Subcellular Fractionation

The homogenate obtained after cell lysis contains various membrane-bound organelles that can be further separated into pure fractions by subcellular fractionation. These isolates are used to study specific cellular components, analyze localized protein activity, and are even employed in diagnostics. Fractionation is typically achieved using centrifugation methods, the most common being density-gradient and differential centrifugation.
Differential Centrifugation
Differential centrifugation is...
8.6K
Self-Evaluation: Self-Enhancement and Self-Verification03:00

Self-Evaluation: Self-Enhancement and Self-Verification

Social psychologists have documented that feeling good about ourselves and maintaining positive self-esteem is a powerful motivator of human behavior (Tavris & Aronson, 2008). In the United States, members of the predominant culture typically think very highly of themselves and view themselves as good people who are above average on many desirable traits (Ehrlinger, Gilovich, & Ross, 2005). Often, our behavior, attitudes, and beliefs are affected when we experience a threat to our...
5.7K
Bioavailability Enhancement: Drug Solubility Enhancement01:16

Bioavailability Enhancement: Drug Solubility Enhancement

Body:Bioavailability is a critical factor in determining a drug's effectiveness. It refers to the proportion of a drug that enters the circulation when introduced into the body and is, as a result, able to have an active effect. Enhancing bioavailability is essential for drugs with poor solubility, as it can significantly impact their therapeutic efficacy. Various methods are employed to increase the solubility of drugs, thereby enhancing their bioavailability.Micronization and nanonization are...
226
Bioavailability Enhancement: Drug Permeability Enhancement01:27

Bioavailability Enhancement: Drug Permeability Enhancement

Body:After oral administration, poor permeability often limits the rate at which drugs are absorbed through the intestinal epithelium. Enhancing drug permeability is crucial for effective therapy, and several strategies have been developed to overcome this challenge.One effective strategy involves the use of lipid-based formulations. These formulations enhance dissolution and solubility, targeting physiological mechanisms to increase drug absorption. This includes stimulating bile salt...
191
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
3.2K
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
7.0K