Background: PLGA nanoparticles were found to be actively exocytosed from cells in a previous study in our lab. The exocytosis process can be modulated to increase the retention of nanoparticles within the cells so that the therapeutic efficacy of any drug encapsulated within the nanoparticles is increased. So, we wanted to know which membrane proteins are involved in the exocytosis process of the nanoparticles. The role of VAMP3 and VAMP7, two crucial membrane proteins associated mainly with constitutive and regulated secretion, respectively, in cells, was studied in the context of exocytosis of PLGA nanoparticles.

Materials and Methods: The siRNA-mediated knockdown of VAMP3 and VAMP7 genes was performed in the LN229 cancer cell line and the intracellular accumulation of PLGA nanoparticles was studied by fluorescence microscopy.

Results: There was no significant difference in the intracellular accumulation of the PLGA nanoparticles after siRNA-mediated knockdown of VAMP3 or VAMP7.

Conclusion: This study shows that VAMP3 and VAMP7, which serve as important membrane proteins associated with the conventional constitutive and regulated secretion of different molecules in cells, are not involved in the exocytosis/secretion of PLGA nanoparticles. So, the pathway of intracellular trafficking of PLGA nanoparticles needs to be deciphered as it appears to be a non-conventional one.