title: Comparative Endocytosis Mechanisms and Anticancer Effect of HPMA Copolymer- and PAMAM Dendrimer-MTCP Conjugates for Photodynamic Therapy.
abstract: 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.
authors: Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran, 1417614411, Iran.|Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, 84112-5820, USA.
authors: Raziye
authors: R
authors: Mohammadpour
authors: Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran, 1417614411, Iran.
authors: Shahrokh
authors: S
authors: Safarian
authors: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, 84112-5820, USA.|The Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, 84112-5820, USA.
authors: Brandon
authors: B
authors: Buckway
authors: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, 84112-5820, USA.|Department of Bioengineering, University of Utah, Salt Lake City, UT, 84112-5820, USA.|The Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, 84112-5820, USA.|Utah Center for Nanomedicine, Nano Institute of Utah, University of Utah, Salt Lake City, UT, 84112-5820, USA.
authors: Hamidreza
authors: H
authors: Ghandehari
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D018432:Drug Resistance, Multiple / Q000187:drug effects; D004705:Endocytosis / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D008689:Methacrylates / Q000138:chemical synthesis / Q000737:chemistry*; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry; D010778:Photochemotherapy / Q000379:methods*; D011166:Porphyrins / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D013816:Thermodynamics; D013997:Time Factors
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D050091:Dendrimers; D004337:Drug Carriers; D008689:Methacrylates; C104700:PAMAM Starburst; D011166:Porphyrins; C474617:meso-tetra(4-(o-carboranyl)phenyl)porphyrin; C032802:hydroxypropyl methacrylate
keywords: HPMA; PAMAM; endocytosis; photosensitizer; polymeric architecture