Lipid Nanoparticles-Based Therapy in Liver Metastasis Management: From Tumor Cell-Directed Strategy to Liver Microenvironment-Directed Strategy

Figures & data

Figure 1 Schematic overview of current LNP-based tumor cell-targeting strategies in liver metastasis management (Created with BioRender.com).

Abbreviation: LNP, lipid nanoparticles.

Table 1 Current LNP-Based Strategies in Locoregional Treatment of Liver Metastasis

Procedure	Liposomal Formulation
Transarterial chemoembolization	Liposomal doxorubicin^Citation55
	Bletilla striata polysaccharide polymer^Citation56
Hepatic arterial infusion chemotherapy	PEG-coated 5- fluorouracil^Citation57
	Galactosylated doxorubicin liposomes^Citation59
Radiofrequency ablation	Liposomal doxorubicin^Citation63,Citation64
	Lyso-thermosensitive Liposomal doxorubicin^Citation65–67
Photodynamic therapy	IR780@O2-SFNs/iRGD^Citation71
	ARISP^Citation73
	O2@PFOB@PGL LNPs^Citation72

Abbreviation: LNP, lipid nanoparticles.

Table 2 Registered Clinical Trials Evaluating Liposomal Formulations in Liver Metastasis

Identifier	Year	Status	Phase	Liposomal Formulations	Conditions
NCT00093444	2004	Completed	1	Lyso-thermosensitive liposomal doxorubicin	Metastatic liver tumors
NCT00441376	2007	Completed	1	ThermoDox™ (Thermally sensitive liposomal doxorubicin)	Metastatic liver tumors
NCT00882180	2009	Completed	1	ALN-VSP02(lipid nanoparticles containing siRNA against VEGF and kinesin spindle protein)	Metastatic liver tumors
NCT01158079	2010	Completed	1	ALN-VSP02	Metastatic liver tumors
NCT01464593	2011	Terminated	2	Lyso-thermosensitive liposomal doxorubicin	Colon cancer liver metastasis
NCT01437007	2011	Completed	1	TKM 080301 (lipid nanoparticles containing siRNA against the PLK1 gene product)	Colorectal cancer with hepatic metastases Pancreas cancer with hepatic metastase Gastric cancer with hepatic metastase Breast cancer with hepatic metastase Ovarian cancer with hepatic metastase
NCT02181075	2014	Completed	1	ThermoDox™ (thermally sensitive liposomal doxorubicin)	Metastatic liver tumors

Figure 2 Nonparenchymal components of the tumor microenvironment in liver metastasis (Created with BioRender.com).

Table 3 Current Nonparenchymal-Cell-Targeting LNPs Strategies in Liver Metastasis

Targeted Cell	Ligand	Co-Loaded Cell-Specific Cytotoxic Agent	Reference
Liver sinusoidal endothelial cells	Scavenger receptor	N/A	[80]
	Scavenger receptor	Clodronate	[81]
Kupffer cells	N/A	Clodronate	[84–86]
	N/A	Oxaliplatin	[82]
	Scavenger receptor	N/A	[80]
Hepatic satellite cells	CD44	Capsaicin	[92]
	CD44	Aprepitant	[93]
	Cysteine-end FH peptide	Oxymatrine	[95]
NK cells	N/A	OK-432	[97]

Abbreviation: N/A, not applicable.

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