Sorafenib Nanomicelles Effectively Shrink Tumors by Vaginal Administration for Preoperative Chemotherapy of Cervical Cancer

Abstract

To investigate the potential of sorafenib (SF) in preoperative chemotherapy for cervical cancer to reduce tumor volume, sorafenib micelles (SF micelles) with good stability and high drug loading were designed. SF micelles were prepared by film hydration followed by the ultrasonic method. The results showed that the SF micelles were spherical with an average particle size of 67.18 ± 0.66 nm (PDI 0.17 ± 0.01), a considerable drug loading of 15.9 ± 0.46% (w/w%) and satisfactory stability in buffers containing plasma or not for at least 2 days. In vitro release showed that SF was gradually released from SF micelles and almost completely released on the third day. The results of in vitro cellular intake, cytotoxicity and proliferation of cervical cancer cell TC-1 showed that SF micelles were superior to sorafenib (Free SF). For intravaginal administration, SF micelles were dispersed in HPMC (SF micelles/HPMC), showed good viscosity sustained-release profiles in vitro and exhibited extended residence in intravaginal in vivo. Compared with SF micelles dispersed in N.S. (SF micelles/N.S.), SF micelles/HPMC significantly reduced tumor size with a tumor weight inhibition rate of 73%. The results suggested that SF micelles had good potential for preoperative tumor shrinkage and improving the quality life of patients.

METTL14 decreases FTH1 mRNA stability via m6A methylation to promote sorafenib-induced ferroptosis of cervical cancer

“…The mice were randomly allocated into five groups, each consisting of 5 mice. For xenograft establishment, HCC9 cells, transfected with sh-METTL14, sh-FTH1, or both, were harvested, and 5 × 10 5 HCC9 stable transfected cells were subcutaneously injected into the right flank of each mouse. Tumor volume was measured weekly using a vernier caliper and calculated with the formula: Volume = (length × width 2 /2, where length is the longest diameter of the tumor, and width is the diameter perpendicular to the length.…”

“… 4 However, its clinical utility is hampered by low bioavailability and the development of drug resistance. 5 Thus, understanding the mechanisms underlying resistance to sorafenib is important to enhance its effectiveness in CC treatment.…”