Chimeric Nanoparticle: A Platform for Simultaneous Targeting of Phosphatidylinositol-3-Kinase Signaling and Damaging DNA in Cancer Cells

Phosphatidylinositol-3-kinase (PI3K) signaling has been hijacked in different types of cancers. Hence, PI3K inhibitors have emerged as novel targeted therapeutics in cancer treatment as mono and combination therapy along with other DNA damaging drugs. However, targeting PI3K signaling with small molecules leads to the emergence of drug resistance and severe side effects to the cancer patients. To address these, we have developed a biocompatible, biodegradable cholesterol-based chimeric nanoparticle (CNP), which can simultaneously load PI103, doxorubicin, and cisplatin in a controlled ratiometric manner. Size, shape, and morphology of these CNPs were characterized by dynamic light scattering (DLS), field-emission scanning electron microscopy (FESEM), atomic force microscopy (AFM), and transmission electron microscopy (TEM). Increased amounts of PI103, doxorubicin, and cisplatin were released from CNPs through controlled and continuous manner over 120 h at pH = 5.5 compared to neutral pH. The CNPs showed mu...