In order to maximize the therapeutic effect of a drug, it is necessary to control the release rate of the drug or efficiently deliver it to an accurate target site. In this study, alginate-melanin-methotrexate-perfluorohexane nanoparticles (AMP NPs) were proposed for controlling the drug release by near-infrared (NIR) laser-responsive photothermal- bubbling effect. AMP NPs had a uniform spherical shape with a size of 252.52 ± 0.39 nm and did not show precipitation in PBS buffer for 7 days. Based on the unique light-to-heat conversion properties of melanin, the temperature of AMP NPs rose to about 52.9°C after irradiation with an 808 nm NIR laser with an intensity of 1.5 W/cm2 for 10 min. As the exotherm of melanin reached the phase transition temperature of perfluorohexane (PFH), microbubbles from the AMP NPs solution were generated dramatically. The release rate of methotrexate from AMP NPs increased to 61% after 24 h of laser irradiation due to the heat generation of melanin and bubble generation of PFH in AMP NPs. From these results, it is expected that AMP NPs can be utilized as promising carriers for controlled drug release.