INNOVATING IN NANOFABRICATION
One of the biggest translational bottlenecks for nanomedicine is the difficulty of fabricating nanoparticles reproducibly and at commercial scales. During my PhD, I explored multiple avenues to improve on fabrication methods for layer-by-layer (LbL) nanoparticles, a very exciting class of nanomaterials capable of extensive multifunctionality. While these nanoparticle are very useful, they are also challenging to produce. To improve the scale, throughput, and yields of LbL nanoparticles I incorporated tangential flow filtration (TFF) technology into the nanofabrication process to manage the cumbersome purification steps required for LbL assembly (Correa et al. Advanced Functional Materials 2016). TFF-assisted fabrication improved our synthetic yields by 20-fold and reduced the time to produce NP formulations significantly (from multiple days to a single day). Importantly, this approach was compatible with a diverse set of polymers and nanoparticles and allowed me to begin development of LbL NP libraries to discover novel functionalities (Correa et al. ACS Nano 2020). In addition to these advances, this work also assessed the long-term shelf-lives of LbL nanoparticles in solution and following lyophilization, providing valuable information to industry partners on the stability of this class of nanomedicine.
While TFF-assisted methods improved our ability to produce LbL nanoparticles, certain biomedical applications required further attention. In particular, the gene delivery capabilities of LbL nanoparticles had been explored, but insufficient research had gone into optimizing the synthetic conditions of these materials, which complicates the possibility future clinical translation. In collaboration with one of my colleagues in the Hammond Lab, we conducted the most thorough study to date on the impact of solution conditions, such as ion valency and ionic strength, on the synthesis of siRNA-carrying LbL nanoparticles (Correa and Boehnke et al. ACS Nano 2019). We discovered synthetic conditions that improved loading of siRNA into LbL nanoparticles by 8-fold, which enhanced in vivo gene delivery in a mouse model of ovarian cancer. These findings, combined with my discovery of novel tumor-targeting nanoparticle surface chemistries, enabled a successful collaboration with the Bhatia Lab at MIT to develop a novel nanotheranostic – an LbL nanoparticle capable of both specific gene silencing and noninvasive tumor diagnostics (Boehnke, Correa, and Hao et al. Angewandte Chemie, 2020).
Read more about these innovations here:
Correa S, Choi KY, Dreaden EC, Renggli K, Shi A, Gu L, Shopsowitz KE, Quadir MA, Ben-Akiva E, Hammond PT. Highly Scalable, Closed-Loop Synthesis of Drug-Loaded, Layer-by-Layer Nanoparticles. Adv Funct Mater. 2016;26(7):991-1003.
Correa S, Boehnke N, Barberio AE, Deiss-Yehiely E, Shi A, Oberlton B, Smith SG, Zervantonakis I, Dreaden EC, Hammond PT. Tuning Nanoparticle Interactions with Ovarian Cancer through Layer-by-Layer Modification of Surface Chemistry. ACS Nano. 2020;14(2):2224-37.
Correa S, Boehnke N, Deiss-Yehiely E, Hammond PT. Solution Conditions Tune and Optimize Loading of Therapeutic Polyelectrolytes into Layer-by-Layer Functionalized Liposomes. ACS Nano. 2019;13(5):5623-34.
Boehnke N, Correa S, Hao L, Wang W, Straehla JP, Bhatia SN, Hammond PT. Theranostic Layer-by-Layer Nanoparticles for Simultaneous Tumor Detection and Gene Silencing. Angewandte Chemie International Edition. 2020;59(7):2776-83.