Microsphere improved the tumor targeting of therapeutic oligodeoxynucleotides in tumor-xenografted nude mice

The strategy of using microsphere as a carrier of therapeutic oligodeoxynucleotides (ODN) has been proposed for cancer treatment. The microsphere could offer an advantage with respect to maintaining constant ODN levels in blood and obtaining higher therapeutic ODN concentration at tumor sites. We investigated in vivo pharmacokinetics of [S-35]-labeled antisense oligodeoxynucleotide targeted to dAMP-dependent protein kinase (PKA) RI-α subunit in WiDr (human colon cancer, ATCC CCL218) tumor model of nude mice. After 14 days of cancer-cell inoculation when the weight of tumor reached ∼0.5 g, 0.1 μCi if [S-35]-labeled RI-α antisense ODN was injected alone or with microsphere (PLG-18, polylactic copolymer with cationic surfactant DDAB18). Each organ or tissue (e.g., blood, liver, kidney, muscle, and tumor) was weighed in a total and a portion for radioactivity measurement. Comparing the effect of microsphere coinjection, peak tumor uptake of [S-35]-labeled ODN was significantly increased from 17.7% of injected dose per gram of tissue (ID/g) after 6 h of the injection to 42.5 %ID/g after 24h. In summary, the coinjection of microsphere appears to be an important carrier system for vehiculating antisense oligonucleotide into the tumor tissue in vivo