Co-Delivery of Methotrexate and Nanohydroxyapatite with Polyethylene Glycol Polymers for Chemotherapy of Osteosarcoma

Author:

Ou Lingbin1,Zhang Qiongyu1,Chang Yong2ORCID,Xia Ning2ORCID

Affiliation:

1. School of Medical Technology, Yongzhou Vocational Technical College, Yongzhou 425100, China

2. College of Chemistry and Chemical Engineering, Anyang Normal University, Anyang 455000, China

Abstract

Neoadjuvant chemotherapy is an alternative treatment modality for tumors. Methotrexate (MTX) has been often used as a neoadjuvant chemotherapy reagent for osteosarcoma surgery. However, the large dosage, high toxicity, strong drug resistance, and poor improvement of bone erosion restricted the utilization of methotrexate. Here, we developed a targeted drug delivery system using nanosized hydroxyapatite particles (nHA) as the cores. MTX was conjugated to polyethylene glycol (PEG) through the pH-sensitive ester linkage and acted as both the folate receptor-targeting ligand and the anti-cancer drug due to the similarity to the structure of folic acid. Meanwhile, nHA could increase the concentration of calcium ions after being uptake by cells, thus inducing mitochondrial apoptosis and improving the efficacy of medical treatment. In vitro drug release studies of MTX-PEG-nHA in phosphate buffered saline at different pH values (5, 6.4 and 7.4) indicated that the system showed a pH-dependent release feature because of the dissolution of ester bonds and nHA under acidic conditions. Furthermore, the treatment on osteosarcoma cells (143B, MG63, and HOS) by using MTX-PEG-nHA was demonstrated to exhibit higher therapeutic efficacy. Therefore, the developed platform possesses the great potential for osteosarcoma therapy.

Funder

Natural Science Foundation of Hunan Province

Education Science Planning Project of Hunan Province

Publisher

MDPI AG

Subject

Electrical and Electronic Engineering,Mechanical Engineering,Control and Systems Engineering

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