Osteosarcoma is the most common type of malignant bone tumor in children and young adults, and it is the sixth leading cancer in children under 15 years of age. The prognosis for osteosarcoma is often poor, as 30% of patients with that diagnosis eventually develop lung metastases. The standard clinical treatment consists of presurgical (neoadjuvant) chemotherapy, followed by surgical resection of the primary tumor after the second or third cycle of the year-long chemotherapy regimen. Curcumin is a phytochemical agent that occurs naturally in plants. It is the principle curcuminoid constituent of the spice turmeric, has been investigated for its therapeutic effects on several cell types, including osteosarcoma and other cancers. However, the therapeutic dose and the intracellular uptake are not fully known yet. Curcumin application is currently limited due to its low bioavailability and poor solubility in aqueous medium (11 ng/ml). One possible way to enhance curcumin aqueous solubility and bioavailability is to conjugate its molecules with polymers.<br/>Synthesized in our group amphiphilic invertible polymers (AIPs) can rapidly self-assemble into micellar nanostructures by changing their concentration in aqueous media, reversibly change their macromolecular conformation in response to a changing environment (e.g. polarity), and effectively incorporate (solubilize) curcumin molecules. The effect of responsive AIPs-mediated curcumin delivery on osteosarcoma cells survival was investigated at different concentrations of loaded assemblies using MTS assays. The obtained results show that presence of micellar curcumin essentially reduces cell survival in human osteosarcoma cell lines MG63 (treated with different concentrations of micellar curcumin), KHOS, and LM7. Remarkably, no effect of polymer micelles tested at the same concentrations, on normal cells survival has been observed. The data show that micellar assemblies effectively deliver curcumin and target three different bone cancer cells (MG63, KHOS, and LM7) but not normal primary human osteoblasts (HOBs).

Responsive polymer-mediated targeted delivery of curcumin to osteosarcoma cells

251st National Meeting (2016)

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