Precision targeting in hepatocellular carcinoma: Exploring ligand-receptor mediated nanotherapy

Table 1 Summary of nanoformulations utilizing Glypican-3 as a targeting receptor in hepatocellular carcinoma treatment

Targeting ligand	Particle size	Nanocarrier	Payload	In vitro or/and in vivo results
GC33[54]	100-150 nm	PEG PLGA	Sorafenib	GC33 modified nanoparticles in vitro: Specifically target GPC3-positive HepG2 cells, resulting in cell cycle arrest at G0/1 phase; in vivo: Inhibit the growth of liver cancer and improve the survival rate of tumor-bearing mice
YP7[55]	N/A	Albumin	Paclitaxel	YP-7 bounded-nanoparticles induce rapid target-specific necrotic cell death and increase the concentration of paclitaxel within HCC tumors
Clone 9C2[56]	85-99 nm	TPGS PCL	Sorafenib	9C2 antibody conjugated nanoparticles in vitro: Have a higher cellular uptake and a 7.5-fold increase in IC50 value compared to free sorafenib; in vivo: Can greatly inhibit tumor growth with no significant side effects
Peptide G12[57]	Approximately 100 nm	Liposome	Sorafenib	G12-modified liposomes in vitro: Have enhanced specific-targeting and internalization into GPC3-positive cancer cells; in vivo: Show a superior precise antitumor effect with marked tumor suppression
Peptide[58]	105-117 nm	PEG PLGA	Sorafenib	Peptide-labeled nanoparticles in vitro: Significantly increase cytotoxicity against Hep3B cells; in vivo: Show good uptake and inhibited tumor growth

HCC: Hepatocellular carcinoma; GPC3: Glypican-3.

Table 2 List of different nanoformulations for Asialoglycoprotein Receptor targeted therapy in hepatocellular carcinoma

Targeting ligand	Particle size	Nanocarrier	Payload	In vitro or/and in vivo results
Lactose[64]	Approximately 115 nm	PCL-PEG-CHO	Sorafenib Curcumin	Lactose modified nanoparticles in vitro: Improve the efficiency of loaded drugs and exhibit better cytotoxicity; in vivo: The inhibition rate is 77.4%
Galactose[65]	92-136 nm	PEG PCL; Micelles	Paclitaxel	IC50 values of Gal decorated nanoparticles decreased from 11.7 to 1.1 μg/mL with increasing Gal concentration from 10% to 30%, supporting receptor-mediated endocytosis mechanism
ASP[66]	Approximately 228 nm	Deoxycholic acid	Doxorubicin	ASP modified nanoformulations in vitro: Internalize into HepG2 cells via ASGPR-mediated recognition and inhibit cell proliferation; in vivo: Suppress the tumor growth and reduce the side effects of free DOX
CS[62]	Approximately 80 nm	Chitosan	Simvastatin	CS decorated nanoparticles enhance the cytotoxicity of the loading drug against HepG2 cells owing to its enhanced cellular uptake
LA[67]	Approximately 310 nm	Cholesterol Liposome	Oxaliplatin	LA presents as a promising ligand for targeted drug delivery in the treatment of BEL7402 cancer cells
Pullulan[68]	140-170 nm	PLGA; PBAE	Paclitaxel; Combretastatin A4	Pullulan labeled nanoparticles enhance targeting capability and efficacy in HCC treatment both in vivo and in vitro
Pectin[69]	Approximately 300 nm	Ca(OH)2; NaHCO3	5-Fu	Pectin-based nanoparticles reduced the IC50 value to 0.17 mol/L in HepG2 cells, a significant decrease compared to the 0.45 mol/L IC50 value for free 5-Fu

ASP: Angelica sinensis polysaccharide; LA: Lactobionic acid; CS: Chondroitin sulfate; 5-Fu: 5-fluorouracil; HCC: Hepatocellular carcinoma.

Table 3 Summary of dual-targeted nanoformulations in hepatocellular carcinoma therapy

Ligand 1	Ligand 2	Nanocarrier	Payload	Particle size
Folic acid[100]	Lactobionic acid	Chitosan	5-Fu	163 ± 10 nm
Folic acid[101]	Lactobionic acid	Berberine; Diosmin	Casein micelles	Approximately 200 nm
Glycyrrhetinic acid[102]	Hyaluronic acid	Carbodiimide	Paclitaxe	200-320 nm
Lactobionic acid[103]	Glycyrrhetinic acid	Chitosan; Acrylic acid	DOX	Approximately 274 nm
Lactoferrin[104]	Lactobionic acid/Glycyrrhetinic acid	Phospholipid complex	Sorafenib; quercetin	169 ± 1.5; 230 ± 1.7
Biotin[105]	Lactobionic acid	PEG; PLGA	Curcumin 5-Fu	110-187 nm

5-Fu: 5-fluorouracil; DOX: Doxorubicin.