Nanosomal Microassemblies for Highly Efficient and Safe Delivery of Therapeutic Enzymes.
Enzyme therapy has unique advantages over traditional chemotherapies for the treatment of hyperuricemia, but overcoming the delivery obstacles of therapeutic enzymes is still a significant challenge. Here, we report a novel and superior system to effectively and safely deliver therapeutic enzymes. Nanosomal microassemblies loaded with uricase (NSU-MAs) are assembled with many individual nanosomes. Each nanosome contains uricase within the alkaline environment, which is beneficial for its catalytic reactions and keeps the uricase separate from the bloodstream to retain its high activity. Compared to free uricase, NSU-MAs exhibited much higher catalytic activity under physiological conditions and when subjected to different temperatures, pH values and trypsin. NSU-MAs displayed increased circulation time, improved bioavailability, and enhanced uric acid-lowering efficacy, while decreasing the immunogenicity. We also described the possible favorable conformational changes occurring in NSU-MAs that result in favorable outcomes. Thus, nanosomal microassemblies could serve as a valuable tool in constructing delivery systems for therapeutic enzymes that treat various diseases.
Medicine Engineering Research Center, Chongqing Medical University , Chongqing 400016, China.
Huarong
H
Xiong
Medicine Engineering Research Center, Chongqing Medical University , Chongqing 400016, China.
Yunli
Y
Zhou
Medicine Engineering Research Center, Chongqing Medical University , Chongqing 400016, China.
Qixin
Q
Zhou
Medicine Engineering Research Center, Chongqing Medical University , Chongqing 400016, China.
Dan
D
He
Medicine Engineering Research Center, Chongqing Medical University , Chongqing 400016, China.
Shengli
S
Wan
Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University , Chongqing 400042, China.
Qunyou
Q
Tan
Medicine Engineering Research Center, Chongqing Medical University , Chongqing 400016, China.
Mi
M
Zhang
Medicine Engineering Research Center, Chongqing Medical University , Chongqing 400016, China.
Xue
X
Deng
Medicine Engineering Research Center, Chongqing Medical University , Chongqing 400016, China.
Jingqing
J
Zhang
D000818:Animals; D000906:Antibodies / Q000276:immunology; D055162:Biocatalysis; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry*; D004797:Enzyme-Linked Immunosorbent Assay; D006461:Hemolysis / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D033461:Hyperuricemia / Q000188:drug therapy; D007700:Kinetics; D008297:Male; D053769:Nanocapsules / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology; D013696:Temperature; D014503:Urate Oxidase / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D014527:Uric Acid / Q000378:metabolism
D000906:Antibodies; D004337:Drug Carriers; D053769:Nanocapsules; D011994:Recombinant Proteins; D014527:Uric Acid; D014503:Urate Oxidase
delivery system; hyperuricemia treatment; microenvironment; nanosomal microassembly; therapeutic enzyme