A Novel Treatment Modality for Malignant Peripheral Nerve Sheath Tumor Using a Dual-Effect Liposome to Combine Photodynamic Therapy and Chemotherapy.

Chin-Tin Chen,Ming-Jen Lee,Po-Chun Peng,Tsuimin Tsai,Hsiung-Fei Chien

doi:10.3390/pharmaceutics12040317

Abstract

Neurofibromatosis type 1 (NF1) is an inherited neurological disorder. Approximately 5–13% of NF1 patients may develop a malignant peripheral nerve sheath tumor (MPNST), which is a neurofibrosarcoma transformed from the plexiform neurofibroma or schwannoma. Given the large size and easy metastasis of MPNST, it remains difficult to be cured by either surgical or conventional chemotherapy. In this study, we investigated the possibility of combining photodynamic therapy (PDT) and chemotherapy to treat MPNST by using a dual-effect liposome (named as PL-cDDP-Ce6), in which a chemotherapeutic agent, cisplatin (cDDP), and photosensitizer, chlorine e6 (Ce6) were encapsulated in the same carrier. The cytotoxic effect of PL-cDDP-Ce6 against MPNST cells was significantly higher than cells treated with liposomal cDDP or Ce6 alone or in combination after light irradiation. Treatment with the dual-effect liposomes in mice bearing xenograft MPNST tumor reveals a significant increase in survival rate compared to those treated with liposomal cDDP and Ce6 in combination. Moreover, there is no weight loss or derangements of serum biochemistry. In conclusion, this study demonstrates the clinical potential and advantage of using this liposomal drug for the treatment of MPNST.

Highlights

Neurofibromatosis type 1 (NF1) is one of the autosomal dominant neurological disorders worldwide
We have previously shown that high level of serum soluble Axl was found in patients with plexiform neurofibroma and malignant peripheral nerve sheath tumor (MPNST) as compared to that of the patients with skin neurofibroma or controls, indicating the plasma level of sAxl could be a reliable biomarker in NF-1 management [25]
To assess the possibility of using cisplatin to treat MPNST, variable dose of cisplatin was intravenously injected into the nu/nu nude mice bearing human S462-TY MPNST cells

Summary

Introduction

Neurofibromatosis type 1 (NF1) is one of the autosomal dominant neurological disorders worldwide. Patients with cutaneous tumors appear during late childhood and develop progressively throughout life [1]. More complex neurofibromas such as plexiform neurofibroma surrounding the entire nerve affect as many as 30 percent of adults with NF1 who might normally appear during early childhood [2]. Total excision for these tumors is often challenging due to their size and location [3]. It has been reported that there is a 5–13% lifetime risk to develop MPNST for NF1 patients; the relative risk is a lot higher for those patients with large plexiform neurofibromas [3,5]

Methods

Results

Conclusion