Delivering Combination Chemotherapies and Targeting Oncogenic Pathways via Polymeric Drug Delivery Systems

The side-effects associated with chemotherapy necessitates better delivery of chemotherapeutics to the tumor. Nanoparticles can load higher amounts of drug and improve delivery to tumors, increasing the efficacy of treatment. Polymeric nanoparticles, in particular, have been used extensively for chemotherapeutic delivery. This review describes the efforts made to deliver combination chemotherapies and inhibit oncogenic pathways using polymeric drug delivery systems. Combinations of chemotherapeutics with other drugs or small interfering RNA (siRNA) combinations have been summarized. Special attention is given to the delivery of drug combinations that involve either paclitaxel or doxorubicin, two popular chemotherapeutics in clinic. Attempts to inhibit specific pathways for oncotherapy have also been described. These include inhibition of oncogenic pathways (including those involving HER2, EGFR, MAPK, PI3K/Akt, STAT3, and HIF-1α), augmentation of apoptosis by inhibiting anti-apoptosis proteins (Bcl-2, Bcl-xL, and survivin), and targeting dysregulated pathways such as Wnt/β-catenin and Hedgehog.