Intratracheal Administration of Hyaluronan-Cisplatin Conjugate Nanoparticles Significantly Attenuates Lung Cancer Growth in Mice

To determine aerosol administration capability and therapeutic efficacy of the new formulation of hyaluronan cisplatin conjugates, HylaPlat™ (HA-Pt), for lung cancer treatment. In vitro formulation stability test, 2D and 3D spheroid cell culture and in vivo efficacy studies using mouse orthotopic allograft models were conducted. The HA-Pt effectively attenuated cell growth in 2D and 3D cultures with IC50 of 2.62 and 5.36 μM, respectively, which were comparable to those with unconjugated control cisplatin-dependent growth inhibition (IC50 1.64 and 4.63 μM, respectively). A single dose of either 7.5 or 15 mg/kg HA-Pt (cisplatin equivalent) by intratracheal aerosol spray 7 days after Lewis lung carcinoma (LLC) cell inoculation markedly inhibited growth of LLC allografts in mouse lungs and resulted in a 90 or 94% reduction of tumor nodule numbers, respectively, as compared to those from the PBS control. Cancer stem cells and cisplatin resistant cells marker, CD44 expression decreased in the tumor nodules of the HA-Pt but not in those of cisplatin treated groups. The current study suggests that an intratracheal aerosol administration of the HA-Pt nanoparticles offers an effective strategy for lung cancer treatment and this treatment may induce only limited cisplatin resistance.