Spherical polymeric nanoconstructs for combined chemotherapeutic and anti-inflammatory therapies

Abstract

Nanoparticles can simultaneously deliver multiple agents to cancerous lesions enabling de facto combination therapies. Here, spherical polymeric nanoconstructs (SPNs) are loaded with anti-cancer - docetaxel (DTXL) - and anti-inflammatory - diclofenac (DICL) - molecules. In vitro, combination SPNs kill U87-MG cells twice as efficiently as DTXL SPNs, achieving a IC₅₀ of 90.5nM at 72h. Isobologram analysis confirms a significant synergy (CI=0.56) between DTXL and DICL. In mice bearing non-orthotopic glioblastoma multiforme tumors, combination SPNs demonstrate higher inhibition in disease progression. At 70days post treatment, the survival rate of mice treated with combination SPNs is of about 70%, against a 40% for DTXL SPNs and 0% for free DTXL. Combination SPNs dramatically inhibit COX-2 expression, modulating the local inflammatory status, and increase Caspase-3 expression, which is directly related to cell death. These results suggest that the combination of anti-cancer and anti-inflammatory molecules constitutes a potent strategy for inhibiting tumor growth.

Keywords: Cancer inflammation; Combinatorial therapy; Nanoparticles; Tumor microenvironment.