Table 1.

PTT combined with hybrid nanosystems as multimodal therapy in HCC.

NPs	Experimental Protocol	Conclusions	References
Lecithin-modified Bi nanoparticles (Bi-Ln NPs)	24 VX2 HCC rabbits were randomly divided into 4 groups, as follows: group A (IA Bi-Ln NPs + NIR Laser); group B (IV Bi-Ln NPs + NIR Laser); group C (IA PBS + NIR Laser); and group D (IA PBS).	Group A displayed a remarkably superior TIR, a higher tumor necrosis rate and an increased apoptosis rate, compared to all other groups. Transcatheter IA combined with IPTT is safe and effective in killing tumor cells and inhibiting tumor growth, and could be applied in HCC soon.	[114] (Zhou, J. et al., 2020)
Galactosylated polymer/gold nanorod nanocomposites: PHEA-g-BIB-pButMA)-g-PEG-GAL embedding AuNRs-C12 and loaded with SOR or LEN i.e., (SOR-NPs) and (LEN-NPs)	Anticancer activity of the SOR-NPs and LEN-NPs was assessed for two HCC cell lines and compared to NHDF. Cells were seeded in a 96-well plate with a density of 1.0 × 104 cells per well (200 μL) and grown for 24 h in a DMEM. Successively, the medium was replaced with a dispersion of SOR-NPs or LEN-NPs. Drug release profiles were evaluated by irradiating the dispersion of nanoparticles with a diode NIR laser (λ = 810 nm, at a power = 0.7 W/mL for 5 or 20 min, at different scheduled time intervals (0 h, 1 h, 3 h, and 6 h). Anticancer activity of the SOR-NPs and LEN-NPs was studied with (810 nm diode laser for 300 s (for SOR-NPs P = 10 W, for LEN-NPs P = 6 W) and without NIR exposure.	The hybrid nanosystems SOR-NPs and LEN-NPs (diameter of about 214 nm and 148 nm, respectively), demonstrated optimum NIR photothermal conversion, high drug loading, and excellent NIR-driven drug release enhancement. These smart drug-loaded hybrid nanosystems for NIR-triggered chemo-phototherapy in HCC with high biocompatibility entered the cancer cells overexpressing ASGPR, where they can release heat and drugs. The innovative approach potentially overcomes MDR in cancer and is a multimodal tool capable of selectively recognizing and killing HCC cells through dual-mode therapy.	[115] (Giammona, G. et al., 2022)
SQ890 was encapsulated with a GSH-sensitive polymer (PLGA-SS-mPEG) to obtain biocompatible SQ890@Fe NPs	Treatment of HepG-2 cells with different concentrations of SQ890@Fe NPs showed the potential to infiltrate cancer cells. The tumoricidal efficacy of SQ890@Fe NPs in vivo in mice, after anesthetization and 808 nm illumination (1 W/cm2) for 5 min, increased the temperature at the tumor sites above 50 °C in 5 min, which led to tumor ablation.	Combined PTT and ferrotherapy on SQ890@Fe NPs demonstrated increased efficacy and safety in the treatment of HCC both in vitro and in vivo by mutually promoting two treatment mechanisms.	[116] (Tang, L. et al., 2022)
HPW@PANI nanorods	HPW@PANI nanorods were applied for in situ NIR-II PTT in orthotopic HCC in rabbits. 1064 nm laser energy was delivered through an optical fiber inserted interventionally into the VX2 primary tumor, with the protocol being tested for different laser power densities for primary tumor ablation, inhibition of distant tumors, and suppression of peritoneal metastases.	HPW@PANI nanorods prepared via oxidative chemical polymerization exhibited strong NIR-II absorption, higher photothermal conversion efficiency, and excellent biocompatibility. In vivo experiments proved that in situ NIR-II PTT could ablate primary tumors, inhibit distant tumors, and suppress peritoneal metastasis, opening new avenues for the management of deeply camouflaged solid tumors.	[120] (Tian, C. et al., 2022)
Multifunctional Oxa@MIL-PDA-PEGTK NPs	After preparation, the Oxa@MIL-PDA-PEGTK NPs were tested for the cumulative release of oxaliplatin and the photothermal effect at different concentrations of NPs using CW irradiation with an 808 nm laser (for 400 s, at a power density of 1 W/cm2). HCC cell line MHCC97H, HCC cell line PLC/PRF/5 and the normal hepatic epithelial cell line L02 were used. Cancer cells were incubated with 100 μg/mL Oxa@MIL-PDA-PEGTK NPs for 4 h, and either left untreated or exposed to 808 nm laser irradiation for 10 min at a power density of 2.0 W/cm2. PLC/PRF/5 cells (1 × 106) were diluted in 100 μL PBS and injected subcutaneously into the right axillary region of male BALB/C-nu mice (5 weeks old). Biodistribution of NPs and photothermal imaging, in vivo tumor growth inhibition, and biochemical examination and pathological analysis of mice were studied.	This multifunctional NP-based DDS could effectively deliver chemotherapeutic agents to tumors. In vitro experiments demonstrated Fe2+ release at tumor sites, increased ROS generation in laser-irradiated cancer cells, while exhibiting low cytotoxicity in non-cancerous cells, facts confirmed by in vivo studies. Design of novel TME-responsive nanoplatforms will soon improve the cure of HCC.	[121] (Huang, R. et al., 2023)