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Table 4 Summary of LNP-based mRNA delivery strategies targeting APCs and T cells

From: mRNA nanodelivery systems: targeting strategies and administration routes

Delivery systems

Formulation (mol%)

Administration Route

Targeting features

Properties of mRNA NPs

Target cells

Ref.

Size (nm)

Zeta (mV)

pKa

Passive targeting

 LNP

YK009: DSPC: Chol:DMG-PEG2000

50: 10: 38.5: 1.5

i.m.

Clathrin- and caveolae-mediated endocytosis

Different ester bond position

Two branched saturated tails with different lengths

93.2 ± 3.5

0.9 ± 0.6

6.512

DCs

[208]

 LNP

PPZ-10: DOPE: Chol: C18PEG2000

35: 16: 46.5: 2.5

i.v.

PPZ-A10 (piperazine-based lipids with shorter C10 carbon chains)

98.3

/

7.0

Kupffer cells(60%)

Spleen macrophages(50%)

Spleen DCs(30%)

Liver DCs(20%)

[209]

 LNP

MC3: DOPE: β-sitosterol: DMG-PEG2000

50: 10: 38.5: 1.5

i.m.

DOPE and β-sitosterol

95 ± 5

-0.1 ± 3

/

DCs

[210]

 LNP

C14-4: DOPE: Chol (7α-hydroxycholesterol): DMG-PEG2000

35: 16: 46.5: 2.5

/

25% 7α- hydroxycholesterol

~100

~-8

~6.25

Primary human T cells

[211]

 PLN

PLGA core

Lipid layer (70% DOPE + 30% DOTMA)

/

70% DOPE and 30% DOTMA

~250

~-10

/

DCs

[212]

 PLN

cationic polymer (SW-01) core

PEG-lipid shell

i.m.

Size

Lipid composition

~200

/

/

DCs at injection site

DCs in spleens and lymph nodes

[213]

Active targeting

 LNP

DLin-DMA: DSPC: Chol (mannosylation): DMG-PEG2000

40: 10: 48: 2

i.m.

i.d.

Active targeting (Mannosylation)

Disaccharide

151.1 ± 0.86

/

/

APCs

[214]

 LNP

ALC-0315: PC: Chol: PEG-lipid

50: 10: 38.5: 1.5

Conjugated with anti-CD5 antibody

i.v.

Active targeting (anti-CD5 antibody)

80

/

/

T cells

[215]

 LNP

PbAE/ PGA-anti-CD8

i.v.

Active targeting (anti-CD8 antibody)

106.9 ± 7.2

4±2

/

T cells

[216]

 APN

MC3: DSPC: Chol: DMPE-PEG2000

50: 10: 38.5: 1.5

Conjugated with pMHCI molecules

i.v.

Active targeting (pMHCI molecules)

107.9 ± 7.34

-22.73 ± 4.7

/

Ag-specific T cell subsets

[217]