Combination chemotherapy and photodynamic therapy of targetable N-(2-hydroxypropyl)methacrylamide copolymer–doxorubicin/mesochlorin e6-OV-TL 16 antibody immunoconjugates

摘要: Abstract The aim of this study was to evaluate the combination chemotherapy and photodynamic therapy N -(2-hydroxypropyl)methacrylamide (HPMA) copolymer-bound doxorubicin (DOX) mesochlorin e 6 (Mce ) targeted with an OV-TL 16 monoclonal antibody (P-DOX-Ab P-Mce -Ab, respectively) in nude mice bearing human ovarian OVCAR-3 carcinoma xenografts. P-DOX-Ab -Ab were synthesized by first conjugating DOX or Mce HPMA copolymer precursor (Mw=21 000), then reacting antibody. immunoconjugates purified size exclusion chromatography on Superose column analyzed. concentration tissues determined a fluorescence assay. Eighteen hours after administration, tumors received light dose 220 J/cm 2 from KTP 650-nm dye-laser. had polymer:drug:protein weight ratios 32:3:62 26:2:72, corresponding molecular approximately 4:14:1 3:8:1, respectively. biodistribution results indicated that percentage total administered reached 1% for nontargeted conjugate at 18 h while 13 times higher. Nude xenografts one i.v. (2.2 mg/kg equivalent) (1.5 irradiation achieved xenograft cure rate more than 60%. incorporation dramatically enhanced accumulation concomitant increase therapeutic efficacy therapy, which may probably be attributed both targeting permeability retention (EPR) effects.