The exploration and utilization of nanocarriers for the delivery of therapeutics in vivo has led to dramatic improvements in the efficacy of various therapies. Over the past few years, intense research and development of novel platforms has resulted in drug delivery vehicles such as polymeric nanoparticles, micelles, immunoconjugates, DNA-polymer conjugates, dendrimers and liposomes. Clinically, the success of these carriers has been limited by the lack of control over size, chemical composition, uniformity, cell targeting and ability to consistently load and release known amounts of cargo. A recent breakthrough from the DeSimone laboratory has led to the production of monodisperse, shape-specific particles from an extensive array of organic precursors. This particle fabrication technology, called PRINT (Particle Replication In Non-wetting Templates), takes advantage of the unique properties of elastomeric molds comprised of a low surface energy perfluoropolyether network.
Understanding the interdependent role of particle size, shape, surface, and matrix composition on the intracellular pathway will lead to a deeper knowledge of the fate of organic nanoparticles in vivo. The advent of “calibration quality” particles using PRINT allows for the elucidation of mechanisms by which organic particles of controlled size, shape, site-specific surface chemistry, tunable particle matrix composition, and tunable modulus undergo endocytosis. Obtaining knowledge about the endocytic pathway used from “calibration quality” particles should lead to crucial information required for not only enhancing specific cellular internalization, but also manipulating the intracellular location of particles, and minimizing cytotoxic effects. Once the mechanisms of internalization are established, it is then possible to use these findings to better engineer the intracellular release of specific cargos. This information, in combination with ongoing efforts to understand the biodistribution of shape controlled particles, will help to establish rules toward the rational design of nanocarriers for effective in vivo delivery of various cargos, especially those cargos that need to be internalized into cells such as siRNA and antisense oligonucleotides.