Synthesis of Doxorubicin-Loaded Nanobubble and Its Effect on Targeted Therapy for Patients with Ovarian Cancer

Abstract

Nanomedicine has developed rapidly for improving the solubility of anti-cancer drugs, prolonging the circulation time in the body, and enhancing the accumulation in the lesion through the enhanced permeability and retention (EPR) effect. First, a new type of dithiolane trimethylene carbonate (MGN) was synthesized, and an amphiphilic polymer PEG-P (ERF-MGN) was synthesized based on MGN and trimethylene carbonate (ERF). Then, N-hydroxysuccinimide (NHS)-PEG-P (ERF-MGN) was prepared by further polymerizing NHS, which was amidated with polypeptide to obtain CC11-PEG-P (ERF-MGN). Finally, it was reacted with PEG-P (ERF-MGN) (mass ratio was 1:4), and CC11-PS was made by solvent exchange method. Through pH gradient method, doxorubicin (Dox) was loaded to prepare Dox nanobubble (CC11-PS-Dox). The prepared nanobubble was compared with the commonly utilized polyethylene glycol liposome Dox (Lipo-Dox) for tumor suppression, and CC11-PS-Dox had a relatively higher tolerated dose. After intravenous administration at a dose of 150 mg/kg, tumor growth in ovarian cancer mice bearing SKOV-3 was effectively inhibited, toxic and side effects were reduced, and the survival time of mice was dramatically increased (P < 0.05). In addition, CC11-PS-Dox was configured as a solution injected into patients with ovarian cancer, phosphate buffer saline (PBS) was injected as a control, and the tumor was irradiated with near-infrared laser (NIR). The tumor’s warming range was detected, and the tumor tissue was removed and stained with hematoxylin-eosin (HE) to observe the growth of the tumor. The results showed that CC11-PS-Dox + NIR can promote the tumor to heat up to 55 °C or more, while PBS + NIR can only promote the tumor to heat up to 37 °C. HE staining results showed that CC11-PS-Dox + NIR can promote tumor loss and cause cell damage. Therefore, it was verified that CC11-PS-Dox can be adopted for photothermal treatment of ovarian cancer.