The significant impact of drug-loaded nanocarriers on cancer chemotherapy lies in the ability to specifically target to tumors with alleviated systemic toxicities. In the current study, a versatile and scalable method has been developed to construct fiber rods from electrospun fibers by ultrasonication using encapsulated NaCl nanoparticles as void-precursors. The shape effects of doxorubicin (DOX)-loaded fiber rods with an average diameter of around 500 nm and different lengths are determined on the blood circulation, tumor accumulation and cellular uptake. Compared with microspheres, fiber rods indicate an up to 4-fold higher accumulation in tumors and an up to 3-fold longer terminal half-life of plasma DOX levels after intravenous injection. Fiber rods with shorter lengths show a significantly higher in vitro cytotoxicity to tumor cells, a higher DOX accumulation and cell necrosis in tumors, and a significantly lower metastasis in lungs. Among fiber rods with different lengths, fiber rods with an average length of 2 mu m induce significantly higher inhibition on tumor cell proliferation and induction of cell apoptosis, as wells as no detectable metastatic nodules in lung sections. Therefore, the shape effects of electrospun fiber rods hold great potential for enhancing systemic circulation and directing biodistribution to improve therapeutic outcomes. (C) 2016 Elsevier B.V. All rights reserved.