Polyamidoamine dendrimer-mediated survivin antisense oligonucleotide inhibits the growth of subcutaneously transplanted colorectal cancer in nude mice / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the inhibitory effects of survivin antisense oligonucleotide (survivin-ASODN) mediated by polyamidoamine dendrimer (PAMAM) against the growth of subcutaneously transplanted colorectal cancer in nude mice.</p><p><b>METHODS</b>Nude mouse models bearing colorectal cancer was established by subcutaneous injection of SW620 cells. Survivin- OSADN (300 microg/L) was mixed with 4.06 microg/L PAMAM or liposome to prepare two transfection complexes, and their morphologies were observed by transmission electron microscope. The particle size of the prepared complexes was determined by laser particle size analyzer, and the zeta potential was measured. The encapsulation efficiency and the DNA release rate in vitro were determined by ultraviolet spectrophotometer. The transfection complexes were then directly injected into the xenografts of the tumor-bearing nude mice. The tumor volume changes were observed, and the expression of survivin in the transplanted tumor was measured by Western blotting.</p><p><b>RESULTS</b>The PAMAM-survivin-ASODN complex had a significantly smaller diameter and greater zeta potential than liposome-survivin-ASODN (P<0.01 and 0.05, respectively). The encapsulation efficiency was comparable between the two complexes. In in vitro condition, PAMAM-survivin-ASODN allowed sustained survivin-ASODN release for as long as 14 days, as compared with the 5 days for the liposome complex. After injection into the tumor xenografts, PAMAM-survivin- ASODN resulted in significantly lower expression of survivin protein in the transplanted tumors (P<0.05), and also in significantly greater reduction of the tumor volume than the liposome complex (P<0.05).</p><p><b>CONCLUSION</b>PAMAM can effectively deliver survivin-ASODN into transplanted colorectal tumor cells to reduce the expression of survivin and inhibit the tumor growth.</p>