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Updated: Mar 3, 2026
Near Infrared Photoimmunotherapy for Mouse Models of Pleural Dissemination
Published on: February 9, 2021
Inhibition of P-glycoprotein using photoimmunotherapy in peritoneal metastasis mouse model
Kaitlyn A Moore1, Brian Schnoor1, Kathryn L McNaughton1
1Fischell Department of Bioengineering, University of Maryland, College Park, Maryland, USA.
Abstract:
Up to 80%-90% of recurrent peritoneal metastasis cases exhibit resistance to multiple chemotherapy agents. A major contributor to this multidrug resistance is the active efflux of chemotherapeutics by P-glycoprotein (P-gp), also known as ATP-binding cassette subfamily B member 1 (ABCB1) transporter and multidrug resistance protein 1 (MDR1). Clinical attempts to inhibit P-gp using small molecule inhibitors have been limited by systemic toxicity or poor tumor selectivity, underscoring the need for safer, targeted strategies. To address this challenge, we demonstrated, for the first time, that intraperitoneal photoimmunotherapy (PIT) using a photoimmunoconjugate (PIC) can inhibit the function of P-gp in a mouse model of peritoneal carcinomatosis. PIC was synthesized and characterized, and a sterile filtration protocol was implemented for its in vivo administration and intraperitoneal PIT application. To assess P-gp function following low-dose PIT, in vivo tumor cells were isolated and evaluated for intracellular accumulation of a well-established P-gp substrate (Rhodamine 123). PIC-PIT significantly increased intracellular Rhodamine 123 retention, indicating effective reduction of P-gp activity. This study provides the first in vivo evidence that PIT can inhibit P-gp function, offering a promising, targeted approach to overcoming chemoresistance while avoiding the systemic toxicity associated with conventional P-gp inhibitors.
Insights
Photoimmunotherapy (PIT) offers a novel way to overcome chemotherapy resistance in peritoneal metastasis by inhibiting P-glycoprotein (P-gp) efflux. This targeted approach shows promise for improving treatment efficacy and reducing systemic toxicity.
Area of Science:
- Oncology
- Biotechnology
- Pharmacology
Background:
- Recurrent peritoneal metastasis often exhibits multidrug resistance, frequently mediated by P-glycoprotein (P-gp/ABCB1/MDR1) efflux pumps.
- Conventional P-gp inhibitors face challenges with systemic toxicity and poor tumor selectivity, necessitating alternative therapeutic strategies.
Purpose of the Study:
- To investigate the efficacy of intraperitoneal photoimmunotherapy (PIT) in inhibiting P-gp function in a preclinical model of peritoneal carcinomatosis.
- To establish a safe and targeted method for reducing P-gp activity in the context of chemoresistant peritoneal disease.
Main Methods:
- Synthesis and characterization of a photoimmunoconjugate (PIC) for intraperitoneal administration.
- Assessment of P-gp function by measuring intracellular accumulation of Rhodamine 123 in tumor cells following low-dose PIT in a mouse model.
Main Results:
- Intraperitoneal PIT using the developed PIC significantly enhanced intracellular Rhodamine 123 retention in tumor cells.
- This increased retention indicates a substantial reduction in P-gp efflux activity post-treatment.
- The study demonstrates successful inhibition of P-gp function in vivo via PIT.
Conclusions:
- Photoimmunotherapy presents a novel, targeted strategy for inhibiting P-gp mediated chemoresistance in peritoneal carcinomatosis.
- This approach offers a promising alternative to conventional P-gp inhibitors, potentially minimizing systemic toxicity.
