In this work, lactobionic acid-modified chitosan (CLA) was chosen as an initial material to prepare tumor-targeted nanoparticles (CLA NPs). To improve the nanoparticles' tumor penetration ability, bromelain was then decorated on the surface of CLA NPs to give CLAB NPs. The micromorphology of CLA and CLAB NPs was observed by transmission electron microscopy and scanning electron microscopy. The stability of CLA and CLAB NPs was then investigated at different pH values (4.0–9.0) and physiological environment by dynamic light scattering. Doxorubicin as a model drug was successfully encapsulated into these two nanoparticles and drug release profiles were also investigated at pH 5.5, 6.5 and 7.4, respectively. Cellular uptake and MTT results against HepG2 and SH-SY5Y cells demonstrated that the LA-conjugated tumor-targeting NPs can be efficiently internalized into hepatoma carcinoma cells, leading to higher cytotoxicity than free doxorubicin. CLAB NPs show considerable cell cytotoxicity and are expected to improve the penetration ability and therapeutic effect in the subsequent in vivo studies.
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