One of the drugs used to treat ovarian cancer is cisplatin. However, cisplatin kills normal surrounding tissue in addition to cancer cells. To improve tumor targeting efficiency, our lab uses neural stem cells (NSCs), which migrate directly to ovarian tumors. If free cisplatin is loaded into NSCs for targeted drug delivery, it will kill the NSCs. To prevent the drug cisplatin from killing both the NSCs, we synthesize silica nanoparticles (SiNPs) that act as a protective carrier. The SiNPs encapsulate cisplatin, and then the SiNPs are loaded into NSCs. The big picture here is to maximize efficiency of tumor targeting using NSCs and minimize toxicity to these NSCs using SiNPs. When tested in vivo, the SiNPs leaked cisplatin before reaching the tumor. The goal of this project is to optimize the stability of SiNPs without cisplatin for efficient drug loading. To do this, the concentration of tetraethyl orthosilicate (TEOS), one of the main components of SiNPs, was varied. We hypothesized that the more TEOS added, the more stable the particles will be. The reasoning is that more TEOS means more silicon in the chemical structure of SiNPs, and thus a tightly-packed SiNPs results in a stable particle. Six batches of SiNPs were synthesized: 200 , 400, 800, 1000, 1400, and 1800 µL TEOS. Then, the stability of the SiNPs were checked in both cell media and phosphate buffered saline (PBS). This step is required because the NSCs grow in cell media and the SiNPs will be in PBS when injected into mice. In order for the particles to effectively carry the drug without leakage, they must be stable in both cell media and PBS. Lastly, the SiNPs were characterized using the transmission electron microscope (TEM). They were analyzed for their size, shape, and porosity.

Our results align with our hypothesis: the more TEOS added, the more stable the SiNPs. In the TEM images, white spots were observed in the SiNPs for the 200-800 µL TEOS batches. The white spots were pores. However, the 1000-1800 µL TEOS batches had no pores. This means that those SiNPs are stable in both cell media and PBS. Our next step is to take the unstable particles and make them stable. Since TEOS is an organic substance, we added another organic substance called trimethoxyphenylsilane (PTMS) to the 400 µL TEOS unstable SiNPs. We then checked the stability of these SiNPs in cell media and PBS. TEM imaging proved that the SiNPs do not form pores in either solution with the added PTMS. Thus, more organic substance made the unstable particles stable.

We concluded that the ultimate factor that determines the stability of our microemulsion-synthesized SiNPs (100 nm) in PBS and cell media is the concentration of TEOS. Confirming our hypothesis, the more TEOS added, the more stable the SiNPs will be.

 

PRECISION MEDICINE & DRUG DISCOVERY

Author: Zina Patel

Coauthor(s): J. M. Berlin W. Abidi

Status: Completed Work

Funding Acknowledgment: RO1 Grant Berlin Lab California Institute for Regenerative Medicine (CIRM)