In this paper, alginic acid-poly(2-(diethylamino)ethyl methacrylate) (ALG-PDEA) nanoparticles were successfully prepared in aqueous medium using a polymer-monomer pair reaction system consisting of the anionic alginic acid (ALG) and the cationic 2-(diethylamino)ethyl methacrylate (DEA), without any aid of surfactants or organic solvents. The ALG-PDEA nanoparticles were monodispersed and stable in aqueous solution. Nanoparticles with desired size could be obtained by varying the amount of initiator or changing the concentration of reactants in solution, which renders this system highly controllable. After the ALG moiety was gelled by Ca2+, the stability of the nanoparticles in basic or high salt concentration solutions could be notably enhanced. A pH-sensitive anticancer agent, hydroxycamptothecin (HCPT), was encapsulated in ALG-PDEA nanoparticles, and preliminary in vitro release as well as cytotoxicity experiments were carried out. It is found that this system seems to be a very promising carrier for the loading and delivery of labile drugs, taking into account that the preparation procedure is simple, mild, and organic solvent- and surfactant-free. Moreover, the abundant functional groups on the particle surface, such as carboxyls and hydroxyls, allow subsequent chemical modification, which may further unleash the potential of such a system in either biomedical applications or in the construction of other functional mesoscopic architectures.