The use of laser induced surface plasmons on metal nanoparticles has proven to be an excellent tool for the delivery of molecules like siRNA and DNA into cells. However, a detailed understanding of the basic mechanisms of molecular uptake and the influence of parameters like biological environment is missing. In this study we analyzed the uptake of fluorescent dextrans with sizes from 10 to 2000 kDa, which resembles a wide range of biologically relevant molecules in size using a 532 nm picosecond laser system and 200 nm gold nanoparticles. Our results show a strong uptake-dependence on cell medium or buffer, but no dominant dependence on osmotic conditions. The relation between pulse energy and number of pulses for a given perforation efficiency revealed that multiphoton ionization of water might contribute to perforation. Moreover, a seven-fold uptake-enhancement could be reached with optimized parameters, providing a very promising basis for further studies and applications.