title: Phospholipase A2-responsive antibiotic delivery via nanoparticle-stabilized liposomes for the treatment of bacterial infection.
abstract: Adsorbing small charged nanoparticles onto liposome surfaces to stabilize them against fusion and payload leakage has resulted in a new class of liposomes capable of environment-responsive drug delivery. Herein, we engineered a liposome formulation with a lipid composition sensitive to bacterium-secreted phospholipase A2 (PLA2) and adsorbed chitosan-modified gold nanoparticles (AuChi) onto the liposome surface. The resulting AuChi-stabilized liposomes (AuChi-liposomes) showed prohibited fusion activity and negligible drug leakage. However, upon exposure to either purified PLA2enzyme or PLA2secreted byHelicobacter pylori(H. pylori) bacteria in culture, AuChi-liposomes rapidly released the encapsulated payloads and such responsive release was retarded by adding quinacrine dihydrochloride, a PLA2inhibitor. When loaded with doxycycline, AuChi-liposomes effectively inhibitedH. pylorigrowth. Overall, the AuChi-liposomes allowed for smart "on-demand" antibitoic delivery: the more enzymes or bacteria present at the infection site, the more drug will be released to treat the infection. Given the strong association of PLA2with a diverse range of diseases, the present liposomal delivery technique holds broad application potential for tissue microenvironment-responsive drug delivery.
authors.affiliation: Department of Nanoengineering, University of California, San Diego, La Jolla, California 92093, USA ; Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Soracha
authors.initials: S
authors.lastname: Thamphiwatana
authors.affiliation: Department of Nanoengineering, University of California, San Diego, La Jolla, California 92093, USA ; Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of Nanoengineering, University of California, San Diego, La Jolla, California 92093, USA ; Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Dissaya
authors.initials: D
authors.lastname: Pornpattananangkul
authors.affiliation: Department of Nanoengineering, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Qiangzhe
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Nanoengineering, University of California, San Diego, La Jolla, California 92093, USA ; Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Fu
authors.affiliation: Department of Nanoengineering, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Jiayang
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Nanoengineering, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Jieming
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Marygorret
authors.initials: M
authors.lastname: Obonyo
authors.affiliation: Department of Nanoengineering, University of California, San Diego, La Jolla, California 92093, USA ; Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Liangfang
authors.initials: L
authors.lastname: Zhang
keywords: antimicrobial delivery; enzyme responsive; gold nanoparticle; liposome; phospholipase