Chemotherapy for gastric cancer by finely tailoring anti-Her2 anchored dual targeting immunomicelles

Micelles with high in vivo serum stability and intratumor accumulation post intravenous (i.v.) injection are highly desired for promoting chemotherapy. Herein, we finely synthesized and tailored well-defined anti-Her2 antibody Fab fragment conjugated immunomicelles (FCIMs), which showed interesting dual targeting function. The thermosensitive poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide)118 (PID118) shell with volume phase transition temperature (VPTT: 39 °C) and the anchored anti-Her2 Fab moiety contributed to the passive and active targeting, respectively. The doxorubicin (DOX) loading capacity of such FCIMs was successfully increased about 2 times by physically enhanced hydrophobicity of inner reservoir without structural deformation. The cellular uptake and intracellular accumulation of DOX by temperature regulated passive and antibody navigated active targeting was 4 times of Doxil. The cytotoxicity assay against Her2 overexpression gastric cancer cells (N87s) showed that the IC50 of the FCIMs was ∼9 times lower than that of Doxil under cooperatively targeting by Fab at T > VPTT. FCIMs showed high serum stability by increasing the corona PID118 chain density (Scorona/Nagg). In vivo tissue distribution was evaluated in Balb/c nude mice bearing gastric cancer. As observed by the IVIS® imaging system, the intratumor accumulation of such finely tailored FCIMs system was obviously promoted 24 h post i.v. administration. Due to the high stability and super-targeting, the in vivo xenografted gastric tumor growth was significantly inhibited with relative tumor volume <2 which was much smaller than ∼5 of the control. Consequently, such finely tailored FCIMs with anti-Her2 active and temperature regulated passive dual tumor-targeting function show high potent in chemotherapy.