Mechanisms for delivery of hydrophobic drugs from polymeric nanoparticles to cancer cells

Abstract

Encapsulation of drugs in nanoparticles could facilitate the accumulation of drugs in the tumor leading to less side effects and improved efficacy of the drug compared to conventional non-specific treatment interventions. When developing nanoparticles for drug delivery, aspects such as their interactions with and mechanism for delivery of drugs to the cells are important to investigate. The aim of this work was to determine which mechanisms were responsible for the cellular uptake of the hydrophobic model drug nile red from polymeric nanoparticles in vitro. Various experiments were conducted were prostatic adenocarcinoma cells were incubated with nanoparticles with encapsulated nile red, or with nile red alone. The cellular uptake and intracellular distribution of nile red was evaluated by flow cytometry and confocal laser scanning microscopy. The polymeric nanoparticles were found to mediate a higher intracellular level and a more rapid uptake of encapsulated model drug compared to when the model drug was administered by itself. The mechanism for delivery of the encapsulated model drug was by contact mediated transfer to cytosol rather than endocytosis of nanoparticles or release of payload to medium followed by diffusion into cells, even though the nanoparticles could release some nile red into medium without cells. This could also be exploited for hydrophobic anticancer drugs to improve cancer therapy and therefore potentially have large clinical relevance. Such a contact mediated mechanism of delivery directly to cytosol could enable effective delivery of anticancer drugs directly to the intracellular molecular drug targets. Further experiments could be conducted to examine the properties of the particles and their behavior more in detail, and determine if the particles are taken up in cells or not. To be applied in vivo, the nanoparticles must be tailored to not release their payload during circulation, but after accumulation at the target site. Much research is required to develop suitable carriers for drug delivery, and the nanoparticles must be carefully optimized to the desired properties. Even though the way to go from research to clinical use of nanoparticles in medicine is long, the use of multifunctional nanoparticles for biomedical applications in cancer seems to hold great potential for diagnosis and targeted treatment.