Pegylated liposomes remotely loaded with the combination of doxorubicin, quinine, and indocyanine green enable successful treatment of multidrug-resistant tumors

Emma Grabarnick Portnoy, Alexander V. Andriyanov, Hadas Han, Sara Eyal, Yechezkel Barenholz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Multidrug resistance (MDR) of cancer cells remains a major obstacle to favorable outcomes of treatment with many drugs, including doxorubicin. Most of the clinical trials failed to demonstrate the benefit of the drug efflux transporter P-glycoprotein (P-gp) inhibitors to circumvent P-gp-mediated drug resistance in vivo. The present study explored the therapeutic potential of combined treatment with liposomal doxorubicin, P-gp inhibitor quinine, and the photodynamic therapy (PDT) using indocyanine green (ICG) in the adenocarcinoma drug-resistant tumor model. Liposomes were actively co-remotely loaded with doxorubicin and quinine, and ICG was passively adsorbed. The liposomes were characterized by differential scanning calorimetry (DSC) and cryo-genic transmission microscopy (Cryo-TEM). We found that quinine impaired the crystalline structure of doxorubicin. In vitro, treatment with single agents themselves was insufficient to inhibit the growth of HT-29 MDR1 cells. However, pegylated liposomal doxorubicin and quinine (PLDQ) significantly diminished HT-29 MDR1 cell survival. Furthermore, survival inhibition intensified by the addition of ICG to the PLDQ (ICG + PLDQ). In vivo, ICG + PLDQ significantly decreased tumor growth when combined with tumor irradiation with NIR light (** p < 0.01). ICG + PLDQ + irradiation was superior to single treatments or combinational treatments without irradiation. These findings suggest that ICG + PLDQ can overcome P-gp-mediated MDR in cancer cells.

Original languageAmerican English
Article number2181
JournalPharmaceutics
Volume13
Issue number12
DOIs
StatePublished - 17 Dec 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • ICG
  • Liposomes
  • Multi drug resistance
  • Phototherapy

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