Methotrexate is one of the most effective drugs that is commonly used in the treatment of cancer. However, its application is limited due to low solubility, high toxicity and rapid metabolism. Therefore, in the present study, worm-like polymeric nanoparticles as carrier of methotrexate were prepared using biodegradable copolymers (mPEG-PCL). The impact of nanoparticles' geometry on the loading, delivery and drug's anti-cancer activity was investigated. The di-block copolymer mPEG-PCL was being synthesized by a ring opening polymerization of ɛ-caprolactone in the presence of mPEG as the initiator and Sn(oct) as the catalyst. It was used for the preparation of worm-like micelles and coated with silica, so that their structures are stable after drying. The synthesized copolymers and nanoparticles were characterized by FTIR, HNMR, GPC, XRD, TGA, DLS, and FE-SEM analyses. The efficiencies of drug loading and release of nanoparticles as in vitro, was studied by high performance liquid chromatography. The MTT method was used to estimate the toxicity on MCF-7 cell category. The obtained results showed that the nanoparticles were worm-like particles with less than 150 nm diameter and about 1 µm length. The loading and encapsulation efficiencies of drug by the worm-like nanoparticles were 3.5 ± 0.14% and 65.6 ± 0.12%, respectively, while they were obtained as 2.1 ± 0.08% and 26 ± 0.10%, respectively, for spherical nanoparticles. The methotrexate diffusional behavior of worm-like nanoparticles was compared with that of the spherical ones. On the other hand, the anti-cancer activity of MTX-loaded nanoparticles was more than the free drug. The results of the MTT assay showed strong and dose-dependent inhibition of cell (MCF-7 category) growth by the nanoparticles compared with MTX. The inhibitory concentrations (IC i.e. reduction viability of cell to 50%) obtained for worm-like, spherical nanoparticles and free drug (incubation times 72 h) were 8.25 ± 0.20, 9.15 ± 0.17, 12.28 ± 0.15 µg/mL, respectively. It can be concluded that application of non-spherical nanoparticles is a better and more effective strategy for controlled and slow release of methotrexate in the treatment of cancer.