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Area of Science:

  • Nanomedicine
  • Pharmacology
  • Biotechnology

Background:

  • Delta-9-tetrahydrocannabinol (Δ⁹-THC) possesses antitumor and palliative properties but suffers from poor bioavailability and side effects.
  • Effective drug delivery systems are crucial for optimizing Δ⁹-THC's therapeutic potential in cancer treatment.
  • Developing novel nanocarriers is essential to overcome Δ⁹-THC's limitations and enhance its anticancer efficacy.

Purpose of the Study:

  • To develop and evaluate transferring (Tf) surface-modified Δ⁹-THC-loaded poly(lactide-co-glycolic) nanoparticles (Tf-THC-PLGA NPs) as a novel anticancer therapy.
  • To investigate the cellular uptake mechanisms and interactions of Tf-THC-PLGA NPs with cancer cells using a double-fluorescent strategy.
  • To assess the efficacy of Tf-modified nanoparticles in reducing cancer cell viability.

Main Methods:

  • Synthesis and characterization of Tf-THC-PLGA NPs.
  • Evaluation of nanoparticle internalization in cancer cells using a double-fluorescent labeling technique.
  • Assessment of cell viability following treatment with Tf-THC-PLGA NPs and plain nanoparticles.
  • Inhibition studies to elucidate nanoparticle uptake pathways (cholesterol-dependent and clathrin-mediated endocytosis).

Main Results:

  • Tf-THC-PLGA NPs significantly reduced cancer cell viability to 17%, compared to 88% for plain nanoparticles.
  • Nanoparticle internalization was observed to be slower for Tf-modified NPs compared to plain NPs.
  • Uptake studies confirmed that nanoparticles are internalized via cholesterol-associated and clathrin-mediated endocytosis mechanisms.
  • The double-fluorescent strategy successfully visualized nanocarrier and drug interactions with cancer cells.

Conclusions:

  • Tf-modification of PLGA nanoparticles is a highly promising strategy for Δ⁹-THC-based antitumor therapies.
  • This approach has the potential to maximize sustained drug release at the surface of cannabinoid receptor-bearing cancer cells.
  • Tf-THC-PLGA NPs represent a novel and effective nanomedicine for enhancing Δ⁹-THC's anticancer therapeutic index.