PMID- 37114464
OWN - NLM
STAT- MEDLINE
DCOM- 20230522
LR  - 20231006
IS  - 2040-3372 (Electronic)
IS  - 2040-3364 (Linking)
VI  - 15
IP  - 19
DP  - 2023 May 18
TI  - ZIF-8 metal organic framework nanoparticle loaded with tense quaternary state 
      polymerized bovine hemoglobin: potential red blood cell substitute with 
      antioxidant properties.
PG  - 8832-8844
LID - 10.1039/d2nr06812e [doi]
AB  - Due to several limitations associated with blood transfusion, such as the 
      relatively short shelf life of stored blood, low risk of developing acute immune 
      hemolytic reactions and graft-versus-host disease, many strategies have been 
      developed to synthesize hemoglobin-based oxygen carriers (HBOCs) as universal red 
      blood cell (RBC) substitutes. Recently, zeolite imidazole framework-8 (ZIF-8), a 
      metal-organic framework, has attracted considerable attention as a protective 
      scaffold for encapsulation of hemoglobin (Hb). Despite the exceptional thermal 
      and chemical stability of ZIF-8, the major impediments to implementing ZIF-8 for 
      Hb encapsulation are the structural distortions associated with loading large 
      quantities of Hb in the scaffold as the Hb molecule has a larger hydrodynamic 
      diameter than the pore size of ZIF-8. Therefore to reduce the structural 
      distortion caused by Hb encapsulation, we established and optimized a 
      continuous-injection method to synthesize nanoparticle (NP) encapsulated 
      polymerized bovine Hb (PolybHb) using ZIF-8 precursors (ZIF-8P-PolybHb NPs). The 
      synthesis method was further modified by adding EDTA as a chelating agent, which 
      reduced the ZIF-8P-PolybHb NP size to <300 nm. ZIF-8P-PolybHb NPs exhibited lower 
      oxygen affinity (36.4 +/- 3.2 mm Hg) compared to unmodified bovine Hb, but was 
      similar in magnitude to unencapsulated PolybHb. The use of the chemical 
      cross-linker glutaraldehyde to polymerize bovine Hb resulted in the low Hill 
      coefficient of PolybHb, indicating loss of Hb's oxygen binding cooperativity, 
      which could be a limitation when using PolybHb as an oxygen carrier for 
      encapsulation inside the ZIF-8 matrix. ZIF-8P-PolybHb NPs exhibited slower oxygen 
      offloading kinetics compared to unencapsulated PolybHb, demonstrating successful 
      encapsulation of PolybHb. ZIF-8P-PolybHb NPs also exhibited favorable antioxidant 
      properties when exposed to H(2)O(2). Incorporation of PolybHb into the ZIF-8 
      scaffold resulted in reduced cytotoxicity towards human umbilical vein 
      endothelial cells compared to unloaded ZIF-8 NPs and ZIF-8 NPs loaded with bovine 
      Hb. We envisage that such a monodisperse and biocompatible HBOC with low oxygen 
      affinity and antioxidant properties may broaden its use as an RBC substitute.
FAU - Gu, Xiangming
AU  - Gu X
AUID- ORCID: 0000-0001-9096-5911
AD  - William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio 
      State University, Columbus, OH, 43210, USA. palmer.351@osu.edu.
FAU - Allyn, Megan
AU  - Allyn M
AD  - William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio 
      State University, Columbus, OH, 43210, USA. palmer.351@osu.edu.
FAU - Swindle-Reilly, Katelyn
AU  - Swindle-Reilly K
AUID- ORCID: 0000-0003-1739-0263
AD  - William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio 
      State University, Columbus, OH, 43210, USA. palmer.351@osu.edu.
AD  - Department of Biomedical Engineering, The Ohio State University, Columbus, OH, 
      43210, USA.
AD  - Department of Ophthalmology and Visual Sciences, The Ohio State University, 
      Columbus, OH, 43212, USA.
FAU - Palmer, Andre F
AU  - Palmer AF
AD  - William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio 
      State University, Columbus, OH, 43210, USA. palmer.351@osu.edu.
LA  - eng
GR  - R01 EB021926/EB/NIBIB NIH HHS/United States
GR  - R01 HL126945/HL/NHLBI NIH HHS/United States
GR  - R01 HL138116/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20230518
PL  - England
TA  - Nanoscale
JT  - Nanoscale
JID - 101525249
RN  - 0 (polymerized bovine hemoglobin)
RN  - 0 (Metal-Organic Frameworks)
RN  - 0 (Antioxidants)
RN  - 1318-02-1 (Zeolites)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - 0 (Hemoglobins)
RN  - 0 (Imidazoles)
RN  - 0 (Blood Substitutes)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Humans
MH  - *Metal-Organic Frameworks/pharmacology
MH  - Antioxidants/pharmacology
MH  - *Zeolites/pharmacology
MH  - Endothelial Cells/metabolism
MH  - Hydrogen Peroxide
MH  - Hemoglobins/pharmacology/chemistry
MH  - Imidazoles
MH  - *Blood Substitutes/pharmacology/chemistry
MH  - Oxygen/chemistry
MH  - *Nanoparticles
MH  - Erythrocytes/metabolism
EDAT- 2023/04/28 06:41
MHDA- 2023/05/22 06:42
CRDT- 2023/04/28 04:23
PHST- 2023/05/22 06:42 [medline]
PHST- 2023/04/28 06:41 [pubmed]
PHST- 2023/04/28 04:23 [entrez]
AID - 10.1039/d2nr06812e [doi]
PST - epublish
SO  - Nanoscale. 2023 May 18;15(19):8832-8844. doi: 10.1039/d2nr06812e.