Polysuccinimide (PSI), a polycondensation product of L-aspartic acid by an acid catalyst, reacts with isopropylamine and results in a novel thermo-responsive polymer with biodegradability and biocompatibility. Although the isopropylamine-modifled polysuccinimide (1PA-PSI) has the same side chain structure as that of ordinary thermo-responsive polymer, poly(N-isopropyl acrylamide) (PNlPAAm), IPA-PSI with 45 % of IPA substitution shows irreversible thermo-induced phase transition. This feature is available for protein encapsulation in the nanospheres using temperature change. The dominant factor for the encapsulation is mainly electrostatic interaction between the negative charge of polymer and the positive charge of protein surface. In fact, more than 90 % of hemoglobin can be easily encapsulated in IPA-PSI nanospheres, and which is released from the polymer without any denaturation.