Screening of photosensitizers-ATP binding cassette (ABC) transporter interactions in vitro

Shruti Vig1, Payal Srivastava1,2, Idrisa Rahman1,3,2

  • 1Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA.

Insights

Seven photosensitizers were tested for transport by ATP-binding cassette (ABC) transporters. Rose bengal, redaporfin, and benzoporphyrin derivative are substrates for ABC transporters, potentially causing photodynamic therapy resistance.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Oncology

Background:

  • ATP-binding cassette (ABC) transporters mediate drug efflux from cancer cells, impacting therapeutic efficacy.
  • Understanding photosensitizer interaction with ABC transporters is crucial for optimizing photodynamic therapy (PDT).

Purpose of the Study:

  • To investigate the susceptibility of seven clinically used photosensitizers to ABC transporter-mediated efflux.
  • To determine if specific ABC transporters (P-gp, BCRP, MRP1) affect photosensitizer intracellular accumulation and PDT efficacy.

Main Methods:

  • Utilized human breast cancer cell lines overexpressing P-gp (ABCB1), BCRP (ABCG2), or MRP1 (ABCC1).
  • Assessed photosensitizer intracellular levels via flow cytometry with and without ABC transporter inhibitors.
  • Evaluated cell viability post-PDT to correlate transporter activity with treatment resistance.

Main Results:

  • Rose bengal, benzoporphyrin derivative (BPD), and redaporfin were identified as substrates for P-gp, BCRP, and/or MRP1.
  • Temoporfin, talaporfin sodium, methylene blue, and indocyanine green were not substrates for these ABC transporters.
  • Overexpression of ABC transporters led to PDT resistance for cells treated with rose bengal, redaporfin, and BPD.

Conclusions:

  • Temoporfin, talaporfin sodium, methylene blue, and indocyanine green are not substrates of P-gp, BCRP, or MRP1.
  • Rose bengal, redaporfin, and BPD interact with ABC transporters, influencing their intracellular accumulation and PDT efficacy.
  • ABC transporter substrate status is a potential mechanism for cellular resistance to PDT with specific photosensitizers.

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