Figure 3.

A) Initiation of H1299 lung adenocarcinoma xenografts in athymic nude mice for assessing in-vivo pharmacological efficacy of various treatments. B) Novel targeted drug delivery systems used for treatments. C) Novel treatments in mice bearing H1299 lung adenocarcinoma xenografts. Various treatments including docetaxel, deslorelin-docetaxel conjugates (D-D), Flt23k-NP, RGD-Flt23k-NP and a combination of D-D + RGD-Flt23k-NP were administered either as repeated weekly intravenous injections or a single intratumoral injection. D) Mechanism of action of D-D and RGD-Flt23k-NP in H1299 lung adenocarcinoma xenograft bearing mice. The delivery systems are taken up by cells via receptor mediated mechanisms. The NPs release the plasmid and the VEGF intraceptor is transcribed, translated and transported to the endoplasmic reticulum. The VEGF intraceptor sequesters and ultimately inhibits VEGF secretion. D-D is endocytosed and expected to breakdown to its parent components within cells. In the tumor cells, docetaxel leads to stabilization of tubulins in spindle fibers leading to a G₂/M phase arrest, ultimately causing apoptosis.