PURPOSE: Photochemical internalization is under development for improving macromolecular therapy by inducing photochemical damage to endocytic vesicles. This damage leads to the release of therapeutic macromolecules entrapped in endocytic vesicles into the cytosol. The macromolecules may in this way be able to interact with therapeutic targets instead of being degraded by lysosomal hydrolases. @entity1732 is used in several standard cancer chemotherapy regimens. Its hydrophilic and relatively large chemical structure limits its ability to penetrate membrane structures, which causes the accumulation of @entity1732 in endocytic vesicles. The purpose of this study was to evaluate the therapeutic potential of @entity26158 (AlPcS2a)-based photochemical delivery of @entity1732 . EXPERIMENTAL DESIGN: Three @entity5 of different origin were grown s.c. in BALB/c (nu/nu) @entity19 . The photosensitizer AlPcS2a and @entity1732 were systemically administered and the @entity5 area was exposed to red light when the @entity5 volume had reached 100 mm3. The @entity5 volume was measured frequently after treatment and the time for the @entity5 volume to reach 800 to 1,000 mm3 was selected as the end point. RESULTS: The photochemical delivery of @entity1732 induced a delayed @entity5 regrowth, and in two out of three @entity5 models, lead to 60% complete response, whereas no complete responses were seen after treatment with @entity1732 alone. A statistical model to assess synergism was established. Combination of the photochemical treatment and @entity1732 was found to induce a synergistic delay in @entity5 growth. CONCLUSION: AlPcS2a-based photochemical internalization of @entity1732 induces a synergistic inhibition of @entity5 growth in three different @entity5 models. This treatment combination should be further considered for clinical utilization.

Site-specific drug delivery by photochemical internalization enhances the antitumor effect of XXXX .

@entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'tumors'] @entity26158 :: ('MESH:C064331', 'Chemical') :: ['aluminum phthalocyanine disulfonate'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity1732 :: ('MESH:D001761', 'Chemical') :: ['Bleomycin', 'bleomycin']
@entity1732 :: (MESH:D001761,Chemical) :: ['bleomycin']
