Abstract:

BACKGROUND: Antisense oligonucleotide (ASODN) can inhibit survivin expression which induce tumor cell apoptosis. There are still some problems in malignant tumors gene therapy by survivin such as insufficient gene transfer, no long-term stable expression, enzyme degradation.
OBJECTIVE: To evaluate the antitumour effects of survivin ASODN carried by polyamidoamine (PAMAM) dendrimer liposome on hepatic cancer transplanted subcutaneously in nude mice. 
METHODS: An in vivo model of hepatic cancer was established by injecting SMMC-7721 cells subcutaneously into the flanks of nude mice. The PAMAM dendrimer liposome and PAMAM dendrimer were mixtured with survivin-ASODN respectively to generate the transfection complex. The zeta potential and encapsulating effciency in vitro were determined. When the tumours were palpable, the mixture complex was directly injected into xenografts to observe the size of tumours. The expression of survivin in transplant tumour was measured.
RESULTS AND CONCLUSION: The zeta potential of the PAMAM liposome-survivin-ASODN complex was higher than that of the PAMAM-survivin-ASODN complex (P < 0.05). There was no significant difference of envelopment ratio between PAMAM liposome-survivin-ASODN group and PAMAM-survivin-ASODN group (P > 0.05). The expression of survivin protein and weight in transplanted tumours for the PAMAM liposome-survivin-ASODN group were lower than those for PAMAM-survivin-ASODN group  (P < 0.05). The PAMAM dendrimer liposome can delivery surviving ASODN into hepatic transplanted tumour cells effectively, reduce the expression of surviving and induce tumour cells apoptosis.