title: Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance.
abstract: Tumor drug resistance significantly limits the success of chemotherapy in the clinic. Tumor cells utilize multiple mechanisms to prevent the accumulation of anticancer drugs at their intracellular site of action. In this study, we investigated the anticancer efficacy of doxorubicin in combination with photodynamic therapy using methylene blue in a drug-resistant mouse tumor model. Surfactant-polymer hybrid nanoparticles formulated using an anionic surfactant, Aerosol-OT (AOT), and a naturally occurring polysaccharide polymer, sodium alginate, were used for synchronized delivery of the two drugs. Balb/c mice bearing syngeneic JC tumors (mammary adenocarcinoma) were used as a drug-resistant tumor model. Nanoparticle-mediated combination therapy significantly inhibited tumor growth and improved animal survival. Nanoparticle-mediated combination treatment resulted in enhanced tumor accumulation of both doxorubicin and methylene blue, significant inhibition of tumor cell proliferation, and increased induction of apoptosis. These data suggest that nanoparticle-mediated combination chemotherapy and photodynamic therapy using doxorubicin and methylene blue has significant therapeutic potential against drug-resistant tumors.
authors.affiliation: Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Ayman
authors.initials: A
authors.lastname: Khdair
authors.forename: Di
authors.initials: D
authors.lastname: Chen
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Patil
authors.forename: Linan
authors.initials: L
authors.lastname: Ma
authors.forename: Q Ping
authors.initials: QP
authors.lastname: Dou
authors.forename: Malathy P V
authors.initials: MP
authors.lastname: Shekhar
authors.forename: Jayanth
authors.initials: J
authors.lastname: Panyam
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000464:Alginates / Q000737:chemistry; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001692:Biological Transport; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004143:Dioctyl Sulfosuccinic Acid / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004337:Drug Carriers; D004339:Drug Compounding; D019008:Drug Resistance, Neoplasm; D005260:Female; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008751:Methylene Blue / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D055806:Microvessels / Q000187:drug effects / Q000473:pathology; D053758:Nanoparticles; D010778:Photochemotherapy; D013997:Time Factors
chemical_list: D000464:Alginates; D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D006603:Hexuronic Acids; D004143:Dioctyl Sulfosuccinic Acid; D004317:Doxorubicin; D020723:Glucuronic Acid; D008751:Methylene Blue