title: Inhalable self-assembled albumin nanoparticles for treating drug-resistant lung cancer.
abstract: Direct pulmonary delivery of anti-cancer agents is viewed as an effective way of treating lung cancer. Here, we fabricated inhalable nanoparticles made of human serum albumin (HSA) conjugated with doxorubicin and octyl aldehyde and adsorbed with apoptotic TRAIL protein (TRAIL/Dox HSA-NP). The octyl aldehyde and doxorubicin endowed HSA with significant hydrophobicity that facilitated self-assembly. TRAIL/Dox HSA-NP was found to have excellent particle size (~340nm), morphology, dispersability, and aerosolization properties. TRAIL/Dox HSA-NP displayed synergistic cytotoxicity and apoptotic activity in H226 lung cancer cells vs. HSA-NP containing TRAIL or Dox alone. TRAIL/Dox HSA-NP was well deposited in the mouse lungs using an aerosolizer, and TRAIL and Dox-HSA were found to be gradually released over 3days. The anti-tumor efficacy of pulmonary administered TRAIL/Dox HSA-NP was evaluated in BALB/c nu/nu mice bearing H226 cell-induced metastatic tumors. It was found that the tumors of H226-implanted mice treated with TRAIL/Dox HSA-NP were remarkably smaller and lighter than those of mice treated with TRAIL or Dox HSA-NP alone (337.5±7.5; 678.2±51.5; and 598.9±24.8mg, respectively). Importantly, this improved anti-tumor efficacy was found to be due to the synergistic apoptotic effects of Dox and TRAIL. In the authors' opinion, TRAIL/Dox HSA-NP offers a potential inhalable anti-lung cancer drug delivery system. Furthermore, the synergism displayed by combined use of Dox and TRAIL could be used to markedly reduce doxorubicin doses and minimize its side effects.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 440-746, Republic of Korea.
authors.forename: Seong Ho
authors.initials: SH
authors.lastname: Choi
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 440-746, Republic of Korea.
authors.forename: Hyeong Jun
authors.initials: HJ
authors.lastname: Byeon
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 440-746, Republic of Korea.
authors.forename: Ji Su
authors.initials: JS
authors.lastname: Choi
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 440-746, Republic of Korea.
authors.forename: Lequang
authors.initials: L
authors.lastname: Thao
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 440-746, Republic of Korea.
authors.forename: Insoo
authors.initials: I
authors.lastname: Kim
authors.affiliation: Division of Biotechnology, The Catholic University of Korea, 43-1 Yeokgok 2-dong, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743, Republic of Korea.
authors.forename: Eun Seong
authors.initials: ES
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Catholic University of Daegu, 330 Geumrak 1-ri, Hayang Eup, Gyeongsan si, Gyeongbuk 712-702, Republic of Korea.
authors.forename: Beom Soo
authors.initials: BS
authors.lastname: Shin
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 440-746, Republic of Korea.
authors.forename: Kang Choon
authors.initials: KC
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 440-746, Republic of Korea. Electronic address: ysyoun@skku.edu.
authors.forename: Yu Seok
authors.initials: YS
authors.lastname: Youn
mesh_terms: D000280:Administration, Inhalation; D000327:Adsorption; D000418:Albumins / Q000008:administration & dosage* / Q000737:chemistry; D000447:Aldehydes / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D017209:Apoptosis / Q000187:drug effects; D002232:Carbocyanines / Q000737:chemistry; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000418:Albumins; D000447:Aldehydes; D000970:Antineoplastic Agents; C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D004337:Drug Carriers; D053221:TNF-Related Apoptosis-Inducing Ligand; D004317:Doxorubicin
keywords: Human serum albumin; Inhalation; Nanoparticles; Resistant lung cancer; Self-assembly; TRAIL