A Temperature-Sensitive Phase-Change Hydrogel of Topotecan Achieves a Long-Term Sustained Antitumor Effect on Retinoblastoma Cells

Onco Targets Ther. 2019 Jul 30;12:6069-6082. doi: 10.2147/OTT.S214024. eCollection 2019.

Abstract

Background: Retinoblastoma (Rb) is one of the most common malignancies among children. Following early diagnosis and prompt treatment, the clinical outcome or prognosis of Rb is promising. However, the prognosis or survival rates of patients with late-stage Rb remain poor. Current therapeutic strategies for advanced Rb mainly involve the use of advanced chemotherapeutic options. However, the efficacy of these strategies is not satisfactory. Therefore, the development of novel strategies to achieve a more effective antitumor effect on late-stage Rb is of crucial importance.

Methods and materials: Topotecan was dissolved in phosphate-buffered saline and prepared into a temperature-sensitive phase-change hydrogel (termed Topo-Gel). Moreover, Topo-Gel was injected into tumor tissues formed by Y79 cells (an Rb cell line) in nude mice to examine the long-term release and long-acting antitumor effect of Topo-Gel on Rb tumors.

Results: Topo-Gel transforms from liquid to a hydrogel at near body temperatures (phase-change temperature [T1/2] was 37.23±0.473 °C), and maintains the slow release of topotecan in Rb tumor tissues. Following the subcutaneous injection of Topo-Gel, the treatment induced long-acting inhibition of tumor growth and relieved the adverse effects associated with topotecan. Topo-Gel, a temperature-sensitive phase-change hydrogel, is a slow-release system that prolongs the presence of topotecan in Rb tissues, and preserves the efficacy of topotecan in the long term.

Conclusion: Preparation of topotecan into a temperature-sensitive phase-change hydrogel achieves a long-term sustained antitumor effect on Rb cells, and may be a useful strategy for the treatment of intraocular Rb.

Keywords: long-acting antitumor effect; retinoblastoma; slow-release system; temperature-sensitive phase-change hydrogel.