Polymer architecture can influence biodistribution and the mode of presentation of bioactive agents to cells. Herein delivery, loading efficiency, and mode of cellular entry of polymer conjugates of the photosensitizer Meso‐Tetra (4‐Carboxyphenyl) Porphyrine (MTCP) are examined when attached to hyperbranched amine terminated poly(amido amine) (PAMAM) dendrimer or random coil linear N‐(2‐hydroxypropyl)methacrylamide (HPMA) copolymer containing free amines in the side chains. The in vitro dark cytotoxicity and phototoxicity of MTCP and related conjugates are assessed on mouth epidermal carcinoma (KB) and human adenocarcinoma alveolar basal epithelial (A549) cells. Phototoxicity of polymeric conjugates increases by ≈100 and 4000 fold in KB and A549 cells compared with nonconjugated MTCP. The increase in phototoxicity activity is shown to result from increased rate of cellular uptake, whereas, cellular internalization of MTCP is negligible in comparison with the conjugated forms. The results of this study suggest the superiority of amine‐terminated HPMA copolymer versus PAMAM dendrimer under study for delivery of MTCP. Treatment with various pharmacological inhibitors of endocytosis shows that polymer architecture influences the mechanism of cellular uptake of the conjugated photosensitizer. Results show that polymeric conjugates of MTCP improve solubility, influence the route and the rate of cellular internalization, and drastically enhance the uptake of the photosensitizer. The association of photosensitizers with polymeric carriers can improve solubility, influence the route and the rate of cellular internalization, and drastically enhance the uptake of the photosensitizer. Random coil HPMA copolymer‐MTCP has more chance for physical association with cell membrane than spherical hyperbranched PAMAM‐MTCP. Negatively charged MTCP might be taken up via lipid raft domain on the cell membrane surface.