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Exploring rifamycin cytotoxic potential through targeted liposomal formulations.

Janaina Artem Ataide1, Nina Filipczak2, Satya Siva Kishan Yalamarty2

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This study repurposed the antibiotic rifamycin as a cancer treatment using liposomes for targeted delivery. Antibody conjugation enhanced its cytotoxic effect, showing promise for cancer therapy.

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Area of Science:

  • Oncology
  • Nanotechnology
  • Pharmacology

Background:

  • Drug repositioning offers novel therapeutic strategies for cancer treatment.
  • Antibiotics with antiproliferative properties are potential candidates for cancer therapy.
  • Rifamycin, an antibiotic inhibiting bacterial RNA synthesis, was investigated for its cytotoxic potential.

Purpose of the Study:

  • To explore rifamycin as a potential cytotoxic agent for cancer treatment.
  • To develop liposome-encapsulated rifamycin (Rf-Lp) for enhanced drug delivery.
  • To evaluate the efficacy of antibody-conjugated Rf-Lp for targeted cancer therapy.

Main Methods:

  • Liposomes were formulated as nanocarriers for rifamycin delivery.
  • Rifamycin-loaded liposomes (Rf-Lp) were characterized for particle size, stability, and biocompatibility.
  • Cytotoxic activity was assessed in various tumor cell lines and spheroids.
  • Monoclonal antibody 2C5 (mAb 2C5) was conjugated to Rf-Lp for targeted delivery.

Main Results:

  • Rf-Lp exhibited good physical and chemical stability and low hemolytic potential.
  • Encapsulated rifamycin demonstrated cytotoxic activity against multiple tumor cell lines.
  • Rf-Lp showed enhanced efficacy in a spheroids model, suggesting improved penetration.
  • mAb 2C5 conjugation significantly boosted rifamycin's cytotoxic activity in specific cell lines, especially with short exposure times.

Conclusions:

  • Liposome encapsulation improves rifamycin stability and release kinetics.
  • Antibody-mediated targeting with mAb 2C5 enhances cellular uptake and therapeutic efficacy.
  • Liposome-encapsulated, antibody-conjugated rifamycin is a promising strategy for targeted cancer therapy.