Silver nanoparticles modulate ABC transporter activity and enhance chemotherapy in multidrug resistant cancer

Dávid Kovács1, Krisztina Szőke1, Nóra Igaz1

  • 1Department of Biochemistry and Molecular Biology, University of Szeged, Szeged, Hungary.

Insights

Silver nanoparticles (AgNPs) combat multidrug-resistant (MDR) cancer by inhibiting drug efflux and enhancing chemotherapy. AgNPs show synergistic effects with antineoplastic agents, offering a novel approach against resistant cancer cells.

Area of Science:

  • Nanotechnology in oncology
  • Cancer biology and drug resistance

Background:

  • Multidrug resistance (MDR) in cancer significantly limits chemotherapy efficacy.
  • Novel therapeutic strategies are crucial to overcome MDR cancer phenotypes.
  • Silver nanoparticles (AgNPs) present a potential new avenue for combating resistant cancers.

Purpose of the Study:

  • To investigate the anti-cancer effects of silver nanoparticles (AgNPs) on multidrug-resistant (MDR) cancer cells.
  • To explore the potential of AgNPs in combination therapy for MDR cancer.

Main Methods:

  • Evaluation of AgNPs' anti-proliferative and apoptosis-inducing effects on drug-sensitive and MDR cancer cells.
  • Assessment of AgNPs' impact on the efflux activity of MDR cancer cells.
  • Verification of synergistic interactions between AgNPs and various chemotherapeutic agents.

Main Results:

  • AgNPs demonstrated significant anti-proliferative activity and induced apoptosis in both drug-sensitive and MDR cancer cells.
  • AgNPs inhibited the efflux activity of MDR cancer cells, potentially increasing intracellular drug accumulation.
  • Synergistic effects were observed when AgNPs were combined with six different antineoplastic agents against resistant cells.

Conclusions:

  • Silver nanoparticles exhibit potent anti-cancer properties against MDR cancer cells.
  • AgNPs can enhance the efficacy of existing chemotherapeutic agents by overcoming drug resistance mechanisms.
  • AgNPs hold promise as combinational partners in the clinical treatment of multidrug-resistant cancers.

Related Concept Videos

ABC Transporters: Exporter01:31

ABC Transporters: Exporter

ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...
7.2K
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
6.3K
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.9K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.9K
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
68
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters01:16

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...
116