Oxaliplatin long-circulating liposomes improved therapeutic index of colorectal carcinoma.

ABSTRACT

BACKGROUND: Cytotoxic drugs are non-selective between normal and pathological tissue, and this poses a challenge regarding the strategy for treatment of tumors. To achieve sufficient antitumor activity for colorectal carcinoma, optimization of the therapeutic regimen is of great importance. We investigated the ability of oxaliplatin long-circulating liposomes (PEG-liposomal L-oHP) to provide an improved therapeutic index of colorectal carcinoma. RESULTS: We determined that PEG- liposomes conjugated with cells at 2 h, with a mean fluorescence intensity that was enhanced upon extended induction time. The PEG-liposomal L-oHP induced a significant apoptotic response as compared with free L-oHP, 23.21% ± 3.38% vs. 16.85% ± 0.98%, respectively. Fluorescence imaging with In-Vivo Imaging demonstrated that PEG- liposomes specifically targeted tumour tissue. After intravenous injections of PEG-liposomal L-oHP or free L-oHP, the tumour volume suppression ratio was 26.08% ± 12.43% and 18.19% ± 7.09%, respectively, the percentage increased life span (ILS%) was 45.36% and 76.19%, respectively, and Bcl-2, Bax mRNA and protein expression in tumour tissue was 0.27-fold vs. 0.88-fold and 1.32-fold vs. 1.61-fold compared with free L-oHP, respectively. CONCLUSION: The PEG-liposomal L-oHP exhibited a tendency to target tumour tissue and demonstrated a significantly greater impact on apoptosis compared to free oxaliplatin.