Development of Smart Polymeric Nanocontainers for the Therapy of Head and Brain Malignancies

Abstract

Head and brain tumours account for 2% to 4% of all cancers globally. Despite progress made in diagnosis and adjuvant therapies, they remain a global burden with unsatisfactory survival rates, reduced treatment outcome, poor prognosis and high risks of recurrence. First line chemotherapy drugs used in current regimens lack specificity, which ensues long term and unpleasant side effects for the patient. Encapsulating the chemotherapy drugs within nanocontainers (NCs) is one approach to improving their efficacy and therapeutic outcome as well as reducing side effects. Due to their nano-size and suitable modified surface, polymeric NCs can reach critical areas in the head and brain without causing any damage to the healthy tissue. The aim was to synthesize polymeric NCs capable of carrying and delivering chemotherapy drugs in tumour cells to increase their efficacy and reduce their side effects. Hollow P(MAA-co-MBA-co-NIPAM-co-EGDMA) NCs with dual sensitivity were synthesised and characterized structurally and morphologically throughout the synthesis steps. Daunorubicin, cisplatin, and temozolomide loaded NCs, and free NCs were assessed by haemolysis assay, MTT assay, fluorescence microscopy, western blot, and flow cytometry in rhabdomyosarcoma TE671 cell line and glioblastoma U87 MG cell line. The free NCs showed high biocompatibility and non-toxicity trait with good cellular uptake. Also, the loading capacities were between 27% and 63%, and the release studies showed a sustained release profile for up to 72h. Treatment of rhabdomyosarcoma and glioblastoma cells with different drugs loaded in NCs showed high cancer cell cytotoxicity, variation in induced DNA damage levels, induced apoptosis and cell cycles arrest for 24h and 72h. Overall, smart polymeric NCs showed reliability in carrying and delivering chemotherapy drugs in rhabdomyosarcoma and glioblastoma cells with efficiency in tackling the tumour cells. Our polymeric NCs exhibited excellent potential as a novel therapeutic approach for targeted drug delivery in head and brain tumours. This could be verified in the preclinical models to assess their improved efficacy and reducing side effects of first line cancer therapies. It could further pave the way for clinical trials of head and brain cancers in human patients.