Background: Blood purification therapy for patients overloaded with metabolic toxins or drugs still needs improvement. Blood purification therapies, such as in hemodialysis or peritoneal dialysis can profit from a combined application with nanoparticles. Summary: In this review, the published literature is analyzed with respect to nanomaterials that have been customized and functionalized as nano-adsorbents during blood purification therapy. Liposomes possess a distinct combined structure composed of a hydrophobic lipid bilayer and a hydrophilic core. The liposomes which have enzymes in their aqueous core or obtain specific surface modifications of the lipid bilayer can offer appreciated advantages. Preclinical and clinical experiments with such modified liposomes show that they are highly efficient and generally safe. They may serve as indirect and direct adsorption materials both in hemodialysis and peritoneal dialysis treatment for patients with renal or hepatic failure. Apart from dialysis, nanoparticles made of specially designed metal and activated carbon have also been utilized to enhance the removal of solutes during hemoadsorption. Results are a superior adsorption capacity and good hemocompatibility shown during the treatment of patients with toxication or end-stage renal disease. In summary, nanomaterials are promising tools for improving the treatment efficacy of organ failure or toxication. Key Messages: (i) The pH-transmembrane liposomes and enzyme-loaded liposomes are two representatives of liposomes with modified aqueous inner core which have been put into practice in dialysis. (ii) Unmodified or physiochemically modified liposomal bilayers are ideal binders for lipophilic protein-bound uremic toxins or cholestatic solutes, thus liposome-supported dialysis could become the next-generation hemodialysis treatment of artificial liver support system. (iii) Novel nano-based sorbents featuring large surface area, high adsorption capacity and decent biocompatibility have shown promise in the treatment of uremia, hyperbilirubinemia, intoxication, and sepsis. (vi) A major challenge of production lies in avoiding changes in physical and chemical properties induced by manufacturing and sterilizing procedures.

1.
Ito
S
,
Yoshida
M
.
Protein-bound uremic toxins: new culprits of cardiovascular events in chronic kidney disease patients
.
Toxins
.
2014
;
6
(
2
):
665
78
.
2.
Niwa
T
.
Removal of protein-bound uraemic toxins by haemodialysis
.
Blood Purif
.
2013
;
35
(
Suppl 2
):
20
5
.
3.
Saar-Kovrov
V
,
Zidek
W
,
Orth-Alampour
S
,
Fliser
D
,
Jankowski
V
,
Biessen
EAL
, et al
.
Reduction of protein-bound uraemic toxins in plasma of chronic renal failure patients: a systematic review
.
J Intern Med
.
2021
;
290
(
3
):
499
526
.
4.
Nanotechnologies – terminology and definitions for nano-objects – nanoparticle, nanofibre and nanoplate. ISO/TS 27687:2008(E).
5.
Zhang
Y
,
Sun
T
,
Jiang
C
.
Biomacromolecules as carriers in drug delivery and tissue engineering
.
Acta Pharm Sin B
.
2018
;
8
(
1
):
34
50
.
6.
Kwiatkowski
AJ
,
Stewart
JM
,
Cho
JJ
,
Avram
D
,
Keselowsky
BG
.
Nano and microparticle emerging strategies for treatment of autoimmune diseases: multiple sclerosis and type 1 diabetes
.
Adv Healthc Mater
.
2020
;
9
(
11
):
e2000164
.
7.
Tang
Z
,
Xiao
Y
,
Kong
N
,
Liu
C
,
Chen
W
,
Huang
X
, et al
.
Nano-bio interfaces effect of two-dimensional nanomaterials and their applications in cancer immunotherapy
.
Acta Pharm Sin B
.
2021
;
11
:
3447
64
.
8.
Forster
V
,
Signorell
RD
,
Roveri
M
,
Leroux
J-C
.
Liposome-supported peritoneal dialysis for detoxification of drugs and endogenous metabolites
.
Sci Transl Med
.
2014
;
6
(
258
):
258ra141
.
9.
Ronco
C
,
Bellomo
R
.
Hemoperfusion: technical aspects and state of the art
.
Crit Care
.
2022
;
26
(
1
):
135
.
10.
Wratten
ML
,
Navino
C
,
Tetta
C
,
Verzetti
G
.
Haemolipodialysis
.
Blood Purif
.
1999
;
17
(
2–3
):
127
33
.
11.
Wratten
ML
,
Sereni
L
,
Tetta
C
.
Hemolipodialysis attenuates oxidative stress and removes hydrophobic toxins
.
Artif Organs
.
2000
;
24
(
9
):
685
90
.
12.
Pratsinis
A
,
Zuercher
S
,
Forster
V
,
Fischer
EJ
,
Luciani
P
,
Leroux
JC
.
Liposome-supported enzymatic peritoneal dialysis
.
Biomaterials
.
2017
;
145
:
128
37
.
13.
Chapman
R
,
Harvey
M
,
Davies
P
,
Wu
Z
,
Cave
G
.
Liposome supported peritoneal dialysis in rat amitriptyline exposure with and without intravenous lipid emulsion
.
J Liposome Res
.
2019
;
29
(
2
):
114
20
.
14.
Cave
G
,
Kee
R
,
Harvey
M
,
Wu
Z
.
pH gradient liposomes extract protein bound amitriptyline in peritoneal dialysis-exploratory work
.
Int J Mol Sci
.
2022
;
23
(
19
):
11577
.
15.
Matoori
S
,
Forster
V
,
Agostoni
V
,
Bettschart-Wolfensberger
R
,
Bektas
RN
,
Thöny
B
, et al
.
Preclinical evaluation of liposome-supported peritoneal dialysis for the treatment of hyperammonemic crises
.
J Control Release
.
2020
;
328
:
503
13
.
16.
Shi
Y
,
Tian
H
,
Wang
Y
,
Shen
Y
,
Zhu
Q
,
Ding
F
.
Removal of protein-bound uremic toxins by liposome-supported peritoneal dialysis
.
Perit Dial Int
.
2019
;
39
(
6
):
509
18
.
17.
Shi
Y
,
Wang
Y
,
Ma
S
,
Liu
T
,
Tian
H
,
Zhu
Q
, et al
.
Increasing the removal of protein-bound uremic toxins by liposome-supported hemodialysis
.
Artif Organs
.
2019
;
43
(
5
):
490
503
.
18.
Shen
Y
,
Wang
Y
,
Shi
Y
,
Tian
H
,
Zhu
Q
,
Ding
F
.
Development of liposome as a novel adsorbent for artificial liver support system in liver failure
.
J Liposome Res
.
2020
;
30
(
3
):
246
54
.
19.
Shen
Y
,
Shen
Y
,
Bi
X
,
Li
J
,
Chen
Y
,
Zhu
Q
, et al
.
Linoleic acid-modified liposomes for the removal of protein-bound toxins: an in vitro study
.
Int J Artif Organs
.
2021
;
44
(
6
):
393
403
.
20.
Shen
Y
,
Shen
Y
,
Li
J
,
Ding
F
,
Wang
Y
.
Polyethyleneimine-anchored liposomes as scavengers for improving the efficiency of protein-bound uremic toxin clearance during dialysis
.
J Biomed Mater Res
.
2022
;
110
(
4
):
976
83
.
21.
Sandeman
SR
,
Zheng
Y
,
Ingavle
GC
,
Howell
CA
,
Mikhalovsky
SV
,
Basnayake
K
, et al
.
A haemocompatible and scalable nanoporous adsorbent monolith synthesised using a novel lignin binder route to augment the adsorption of poorly removed uraemic toxins in haemodialysis
.
Biomed Mater
.
2017
;
12
(
3
):
035001
.
22.
Yuan
Z
,
Li
Y
,
Zhao
D
,
Zhang
K
,
Wang
F
,
Wang
C
, et al
.
High efficiency 3D nanofiber sponge for bilirubin removal used in hemoperfusion
.
Colloids Surf B Biointerfaces
.
2018
;
172
:
161
9
.
23.
Chai
Y
,
Liu
Z
,
Du
Y
,
Wang
L
,
Lu
J
,
Zhang
Q
, et al
.
Hydroxyapatite reinforced inorganic-organic hybrid nanocomposite as high-performance adsorbents for bilirubin removal in vitro and in pig models
.
Bioact Mater
.
2021
;
6
(
12
):
4772
85
.
24.
Xiang
Y
,
Bai
Z
,
Zhang
S
,
Sun
Y
,
Wang
S
,
Wei
X
, et al
.
Lead adsorption, anticoagulation and in vivo toxicity studies on the new magnetic nanomaterial Fe(3)O(4)@SiO(2)@DMSA as a hemoperfusion adsorbent
.
Nanomedicine
.
2017
;
13
(
4
):
1341
51
.
25.
Chew
CH
,
Cheng
LW
,
Huang
WT
,
Wu
YM
,
Lee
CW
,
Wu
MS
, et al
.
Ultrahigh packing density next generation microtube array membrane: a novel solution for absorption-based extracorporeal endotoxin removal device
.
J Biomed Mater Res B Appl Biomater
.
2020
;
108
(
7
):
2903
11
.
26.
Wei
Z
,
Peng
G
,
Zhao
Y
,
Chen
S
,
Wang
R
,
Mao
H
, et al
.
Engineering antioxidative cascade metal-phenolic nanozymes for alleviating oxidative stress during extracorporeal blood purification
.
ACS Nano
.
2022
;
16
(
11
):
18329
43
.
27.
Chen
HC
,
Cheng
CY
,
Lin
HC
,
Chen
HH
,
Chen
CH
,
Yang
CP
, et al
.
Multifunctions of excited gold nanoparticles decorated artificial kidney with efficient hemodialysis and therapeutic potential
.
ACS Appl Mater Inter
.
2016
;
8
(
30
):
19691
700
.
28.
Fagugli
RM
,
De Smet
R
,
Buoncristiani
U
,
Lameire
N
,
Vanholder
R
.
Behavior of non-protein-bound and protein-bound uremic solutes during daily hemodialysis
.
Am J Kidney Dis
.
2002
;
40
(
2
):
339
47
.
29.
García Martínez
JJ
,
Bendjelid
K
.
Artificial liver support systems: what is new over the last decade
.
Ann Intensive Care
.
2018
;
8
(
1
):
109
.
30.
Rifai
K
.
Extracorporeal albumin dialysis
.
Hepatol Res
.
2008
;
38
(
Suppl 1
):
S41
45
.
31.
Kuznetsova
DA
,
Gaynanova
GA
,
Vasileva
LA
,
Sibgatullina
GV
,
Samigullin
DV
,
Sapunova
AS
, et al
.
Mitochondria-targeted cationic liposomes modified with alkyltriphenylphosphonium bromides loaded with hydrophilic drugs: preparation, cytotoxicity and colocalization assay
.
J Mater Chem B
.
2019
;
7
(
46
):
7351
62
.
32.
Castelli
F
,
Uccella
N
,
Trombetta
D
,
Saija
A
.
Differences between coumaric and cinnamic acids in membrane permeation as evidenced by time-dependent calorimetry
.
J Agric Food Chem
.
1999
;
47
(
3
):
991
5
.
33.
Ryujin
T
,
Shimizu
T
,
Miyahara
R
,
Asai
D
,
Shimazui
R
,
Yoshikawa
T
, et al
.
Blood retention and antigenicity of polycarboxybetaine-modified liposomes
.
Int J Pharm
.
2020
;
586
:
119521
.
34.
Yen
SC
,
Liu
ZW
,
Juang
RS
,
Sahoo
S
,
Huang
CH
,
Chen
P
, et al
.
Carbon nanotube/conducting polymer hybrid nanofibers as novel organic bioelectronic interfaces for efficient removal of protein-bound uremic toxins
.
ACS Appl Mater Inter
.
2019
;
11
(
47
):
43843
56
.
35.
Marketos
SG
,
Androutsos
G
.
Charcoal: from antiquity to artificial kidney
.
J Nephrol
.
2004
;
17
(
3
):
453
6
.
36.
Ricci
Z
,
Romagnoli
S
,
Reis
T
,
Bellomo
R
,
Ronco
C
.
Hemoperfusion in the intensive care unit
.
Intensive Care Med
.
2022
;
48
(
10
):
1397
408
.
37.
Kim
S
,
Feinberg
B
,
Kant
R
,
Chui
B
,
Goldman
K
,
Park
J
, et al
.
Diffusive silicon nanopore membranes for hemodialysis applications
.
PLoS One
.
2016
;
11
(
7
):
e0159526
.
38.
Chen
HC
,
Lin
HC
,
Chen
HH
,
Mai
FD
,
Liu
YC
,
Lin
CM
, et al
.
Innovative strategy with potential to increase hemodialysis efficiency and safety
.
Sci Rep
.
2014
;
4
:
4425
.
39.
Riediker
M
,
Zink
D
,
Kreyling
W
,
Oberdörster
G
,
Elder
A
,
Graham
U
, et al
.
Particle toxicology and health - where are we
.
Part Fibre Toxicol
.
2019
;
16
(
1
):
19
.
40.
Monica
JCJ
.
FDA’s evolving approach to nanotechnology
.
Food Drug L J
.
2012
;
67
:
405
11
, i.
41.
Graham
UM
,
Tseng
MT
,
Jasinski
JB
,
Yokel
RA
,
Unrine
JM
,
Davis
BH
, et al
.
In vivo processing of ceria nanoparticles inside liver: impact on free-radical scavenging activity and oxidative stress
.
Chempluschem
.
2014
;
79
(
8
):
1083
8
.
42.
Wu
JS
,
Kim
AM
,
Bleher
R
,
Myers
BD
,
Marvin
RG
,
Inada
H
, et al
.
Imaging and elemental mapping of biological specimens with a dual-EDS dedicated scanning transmission electron microscope
.
Ultramicroscopy
.
2013
;
128
:
24
31
.
43.
Borm
P
,
Cassee
FR
,
Oberdörster
G
.
Lung particle overload: old school -new insights
.
Part Fibre Toxicol
.
2015
;
12
:
10
.
44.
Metselaar
JM
,
Lammers
T
.
Challenges in nanomedicine clinical translation
.
Drug Deliv Transl Res
.
2020
;
10
(
3
):
721
5
.
45.
Liu
Y-Y
,
Diana
M
,
Halvax
P
,
Cho
S
,
Légner
A
,
Alzaga
A
, et al
.
Flexible endoscopic single-incision extraperitoneal implant and fixation of peritoneal dialysis catheter: proof of concept in the porcine model
.
Surg Endosc
.
2015
;
29
(
8
):
2402
6
.
46.
Tao
X
,
Thijssen
S
,
Kotanko
P
,
Ho
C-H
,
Henrie
M
,
Stroup
E
, et al
.
Improved dialytic removal of protein-bound uraemic toxins with use of albumin binding competitors: an in vitro human whole blood study
.
Sci Rep
.
2016
;
6
:
23389
.
47.
Reed
RG
.
Kinetics of bilirubin binding to bovine serum albumin and the effects of palmitate
.
J Biol Chem
.
1977
;
252
(
21
):
7483
7
.
48.
Ceryak
S
,
Bouscarel
B
,
Fromm
H
.
Comparative binding of bile acids to serum lipoproteins and albumin
.
J Lipid Res
.
1993
;
34
(
10
):
1661
74
.
49.
Jourde-Chiche
N
,
Dou
L
,
Cerini
C
,
Dignat-George
F
,
Vanholder
R
,
Brunet
P
.
Protein-bound toxins--update 2009
.
Semin Dial
.
2009
;
22
(
4
):
334
9
.
50.
Kokozidou
M
,
Katsargyris
A
,
Verhoeven
ELG
,
Schulze-Tanzil
G
.
Vascular access animal models used in research
.
Ann Anat
.
2019
;
225
:
65
75
.
51.
Valerianova
A
,
Mlcek
M
,
Kittnar
O
,
Grus
T
,
Tejkl
L
,
Lejsek
V
, et al
.
A large arteriovenous fistula steals a considerable part of systemic blood flow during veno-arterial extracorporeal circulation support in a porcine model
.
Front Physiol
.
2023
;
14
:
1109524
.
52.
Shen
Y
,
Liu
T
,
Shi
Y
,
Zhuang
F
,
Lu
J
,
Zhu
Q
, et al
.
Bisphenol A analogs in patients with chronic kidney disease and dialysis therapy
.
Ecotoxicol Environ Saf
.
2019
;
185
:
109684
.
53.
Zhao
R
,
Ma
T
,
Cui
F
,
Tian
Y
,
Zhu
G
.
Porous aromatic framework with tailored binding sites and pore sizes as a high-performance hemoperfusion adsorbent for bilirubin removal
.
Adv Sci
.
2020
;
7
(
23
):
2001899
.
54.
Tsushima
K
,
Koizumi
T
,
Yoshikawa
S
,
Obata
T
,
Kubo
K
.
Polymyxin B immobilized column is effective for hydrochloric acid-induced lung injury in rats
.
Eur J Pharmacol
.
2006
;
535
(
1–3
):
270
9
.
55.
Kuznetsova
NR
,
Sevrin
C
,
Lespineux
D
,
Bovin
NV
,
Vodovozova
EL
,
Mészáros
T
, et al
.
Hemocompatibility of liposomes loaded with lipophilic prodrugs of methotrexate and melphalan in the lipid bilayer
.
J Control Release
.
2012
;
160
(
2
):
394
400
.
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