Self-assembled verteporfin nanoparticles decrease drug efflux by P-glycoprotein without light activation in
Idrisa Rahman1,2, Anju Meda1, Kaitlyn A Moore1
1Fischell Department of Bioengineering University of Maryland College Park Maryland USA.
Bioengineering & Translational Medicine
|July 3, 2026
Summary
Non-illuminated verteporfin nanoaggregates (NanoVP) inhibit P-glycoprotein (P-gp) by targeting mitochondrial ATP production. This light-independent approach enhances chemotherapy efficacy in drug-resistant cancers.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) hinders cancer chemotherapy.
- Photodynamic therapy with verteporfin (VP) shows promise but effects are reversible due to P-gp re-synthesis.
Purpose of the Study:
- Investigate non-illuminated VP nanoaggregates (NanoVP) for light-independent P-gp inhibition.
- Target mitochondrial metabolism to overcome P-gp-mediated MDR in vitro.
Main Methods:
- Utilized drug-resistant cancer cells and NanoVP.
- Assessed mitochondrial oxygen consumption and ATP production.
- Measured P-gp substrate accumulation and antibody binding.
Main Results:
- High NanoVP concentrations (5 μM, 72h) reduced mitochondrial ATP with minimal cytotoxicity.
- Metabolic perturbation sustained P-gp inhibition, enhancing drug accumulation.
- NanoVP treatment improved chemotherapeutic efficacy in resistant cells.
Conclusions:
- Non-illuminated NanoVP offers a novel, light-independent strategy to overcome P-gp-mediated MDR.
- VP acts as a metabolic priming agent, enhancing chemotherapy in resistant cancers.
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