Therapeutic targeting of malignant pleural mesothelioma with a hydrosoluble paclitaxel-hyaluronan conjugate

Malignant pleural mesothelioma (MPM) is an aggressive neoplasia characterized by a poor prognosis. It is usually identified at advanced stages and its management is nowadays still complex because of the lack of effective treatments options. In this regard, drug delivery system has emerged as a promising strategy to target anticancer drugs more precisely to tumor cells. This certainly applies to ONCOFID-P (ON-P), a bioconjugate derived from the chemical linking of Paclitaxel (PTX) to hyaluronan (HA) that confers solubility and mucoadhesiveness to the cytotoxic drug, enhancing selectivity for CD44+ tumor cells. In this study we evaluated the in vitro and in vivo therapeutic efficacy of the bioconjugate ONCOFID-P against MPM in comparison to the free drug PTX. In vitro preliminary data showed that ON-P cytotoxicity against MPM cell lines that express CD44 on the surface, is comparable to PXT. Moreover, the bioconjugate acts by disrupting β-tubulin and induces apoptosis similarly to PTX. In vivo, intraperitoneal injection of ON-P showed more effective than free PXT, reducing tumor growth and prolonging survival of MPM bearing-mice, being simultaneously better tolerated. Overall, these results represent the premises to advance ONCOFID-P as a valid therapeutic approach for loco-regional treatment of MPM.