title: Cationic dendritic starch as a vehicle for photodynamic therapy and siRNA co-delivery.
abstract: Cationic enzymatically synthesized glycogen (cESG) is a naturally-derived, nano-scale carbohydrate dendrite that has shown promise as a cellular delivery vehicle owing to its flexibility in chemical modifications, biocompatibility and relative low cost. In the present work, cESG was modified and evaluated as a vehicle for tetraphenylporphinesulfonate (TPPS) in order to improve cellular delivery of this photosensitizer and investigate the feasibility of co-delivery with short interfering ribonucleic acid (siRNA). TPPS was electrostatically condensed with cESG, resulting in a sub-50nm particle with a positive zeta potential of approximately 5mV. When tested in normal ovarian surface epithelial and ovarian clear cell carcinoma cell culture models, encapsulation of TPPS in cESG significantly improved cell death in response to light treatment compared to free drug alone. Dosages as low as 0.16μM TPPS resulted in cellular death upon illumination with a 4.8J/cm2light dosage, decreasing viability by 96%. cESG-TPPS was then further evaluated as a co-delivery system with siRNA for potential combination therapy, by charge-based condensation of an siRNA directed at reducing expression of manganese superoxide dismutase (Sod2) as a proof of principle target. Simultaneous delivery of TPPS and siRNA was achieved, reducing Sod2 protein expression to 48%, while maintaining the photodynamic properties of TPPS under light exposure and maintaining low dark toxicity. This study demonstrates the versatility of cESG as a platform for dual delivery of small molecules and oligonucleotides, and the potential for further development of this system in combination therapy applications.
authors.affiliation: Nanobioscience Constellation, Colleges of Nanoscale Science and Engineering, SUNY Polytechnic Institute, Albany, NY 12203, United States.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Engelberth
authors.affiliation: Department of Pharmacology, Penn State College of Medicine, Hershey, PA 17033, United States. Electronic address: nhempel@psu.edu.
authors.forename: Nadine
authors.initials: N
authors.lastname: Hempel
authors.affiliation: Nanobioscience Constellation, Colleges of Nanoscale Science and Engineering, SUNY Polytechnic Institute, Albany, NY 12203, United States. Electronic address: mbergkvist@sunypoly.edu.
authors.forename: Magnus
authors.initials: M
authors.lastname: Bergkvist
mesh_terms: D002412:Cations; D016923:Cell Death / Q000187:drug effects; D050091:Dendrimers / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D004359:Drug Therapy, Combination; D005260:Female; D006003:Glycogen / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D010778:Photochemotherapy / Q000379:methods*; D011166:Porphyrins / Q000494:pharmacology / Q000627:therapeutic use; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013213:Starch; D014407:Tumor Cells, Cultured
chemical_list: D002412:Cations; D050091:Dendrimers; D004337:Drug Carriers; D011166:Porphyrins; D034741:RNA, Small Interfering; C016136:tetraphenylporphine sulfonate; D013213:Starch; D006003:Glycogen
keywords: Cationic enzymatically synthesized glycogen; Co-delivery; Photodynamic therapy; Sulfonated porphyrin; TPPS; siRNA