Table 2.

Experimental applications of PTT and PDT for synergistic therapy in HCC.

Photosensitizer	PTT and PDT Protocol	Conclusions	References
Structural variants of phthalocyanine (Pc)	In vivo PTT efficacy of Pcs on S180 tumors was tested. Pcs were injected into the S180 tumor in mice, after which the area was irradiated with a 685 nm laser for 10 min at a power density of 0.2 W/cm2.	By structural adjustment, the authors obtained three Pc derivatives with PTT activity against human HCC. PcC1 had a very good in vivo PTT effect against S180 tumors in carrier mice. Pc molecular dyes are suitable for PTT, for the advanced promotion of Pc molecular dye-based multifunctional phototheranostic agents.	[125] (Li, X. et al., 2018)
CAR-T cell membrane-coated nanoparticles (CIMs)	In vitro antitumor effect was investigated on Huh-7 cell cultures incubated with CIMs, and in vivo after abdominal tumor development with the same cells in BALB/c-nu mice irradiated with an 808 nm laser (0.6 W/cm2, for 5 min).	CIMs demonstrated very good targeting and PTT efficacy, giving rise to a promising method for the treatment of HCC.	[126] (Ma, W. et al., 2020)
Nanoplatform ICG&Cur@MoS2	The PTT properties of ICG&Cur@MoS2 NPs were tested in vitro by irradiation with an 808 nm laser at 2.0 W/cm2 for 5 min on ICG&Cur@MoS2 samples at different concentrations. The effect of PTT-PDT in vitro was investigated after irradiation of different groups of HepG-2 cells incubated with ICG, MoS2, ICG@MoS2 or ICG&Cur@MoS2. The effect of PTT-PDT in vivo was investigated by a randomized study on six groups of mice with abdominal tumors induced by experimental H22 cell line. The NIR groups were irradiated in the tumor area with an 808 nm laser (1.2 W/cm2) for 5 min, at 10 h post-injection. Both body weight and tumor size were measured and recorded carefully.	Cell viability in the ICG&Cur@MoS2 + NIR group was significantly lower than that in the ICG@MoS2 + NIR group. The results can be attributed to the synergistic effect of PTT-PDT and P-gp inhibition. ICG@MoS2 + NIR group tumors were significantly smaller than in MoS2 + NIR group. Compared with the control group, P-gp in HepG-2 cells treated with ICG&Cur@MoS2 was significantly inhibited.	[130] (Li, S. et al., 2021)
1-[2-Hydroxyethyl]-4-[4-(1,2,2-triphenylvinyl) styryl]pyridinium bromide (TPE-Py-OH)	For long-term PDT in vitro, HepG2 cells were incubated with various concentrations of TPE-Py-OH, and then exposed to a blue laser with different durations (450 nm, 30 mW/cm2, 18–45 J/cm2). In vivo multiple light-activated PDT was investigated in a randomized study on 5 groups of 8 animals per group with HCC induced by cell line H22. TPE-Py-OH was intratumorally injected, and further irradiated with a blue laser (450 nm, 100 mW/cm2, 10 min, 60 J/cm2).	TPE-Py-OH as an innovative AIE-active PS could be promising for tracking and PDT ablation of HCC with uninterrupted efficacy.	[133] (Chai, C. et al., 2022)
P(AAm-co-AN)-AuNRs@CeO2-Ce6 (PA/Ce6)	The antitumor effects of PDT/PTT in vitro were studied on HepG2 cells incubated with PA/Ce6, followed by 660 nm and 880 nm laser irradiation for 600 s. The antitumor efficacy of PDT/PTT in vivo was investigated by monitoring the weight and volume of abdominal HCC in 6 groups of mice randomized as follows: IV saline solution; saline + light (808 nm + laser 660 nm); PA/Ce6; PA/Ce6 + 808 nm laser; PA/Ce6 + 660 nm laser; and PA/ce6 + light (808 nm + 660 nm lasers).	Viability of HepG2 cells incubated with PA/Ce6 was reduced after 660 nm and 880 nm laser irradiation. PA/Ce6 could decompose hydrogen peroxide under laser irradiation and attenuate the anaerobic TME, opening up favorable future opportunities for the management of HCC by synergistic PTT and PDT.	[134] (Li, B. et al., 2022)
ICG/Pt@PDA-CXCR4 (IPP-c)	After HepG2 cells were incubated with IPP-c NPs, they were irradiated with an 808 nm laser for 10 min compared with a non-irradiated set. BALB/c nude mice bearing orthotopic SHCC tumors received I.V. IPP-c NPs, after which they were irradiated in the area of liver tumors for 12 min with an 808 nm laser at a dose of 0.8 W/cm2.	CXCR4-targeted multifunctional nanoparticles for mini-invasive phototherapy of orthotopic SHCCs by real-time quantitative optical imaging guidance provide another perspective for constructing a nanoplatform for early-stage HCC phototheranostics.	[143] (Qi, S. et al., 2022)
MnO2-SOR-Ce6@PDA- PEG-FA (MSCPF)	Investigation of the photothermal effect of MnO2 and PDA by irradiating H2O, MnO2 and MnO2@PDA samples irradiated with an 808 nm laser for 10 min at a power of 2 W/cm2. A series of MSCPF solutions (50, 100, 200 μg/mL) at different power densities (0.5–2.0 W/cm2) were applied for the test, and the temperature rise was recorded by an NIR thermal camera. In vitro PTT/PDT efficiency was studied on SMMC-7721 cell cultures irradiated with a laser at 808 nm (for PTT, 1.5 W/cm2) or 660 nm (for PDT, 500 mW/cm2) for 10 min, after incubation with Ce6, MCP and MCPF. The antitumor effect of MSCPF NPs was evaluated in vivo on SMMC-7721 tumor-bearing mice randomly divided into four groups.	In comparison with H2O, MnO2 showed a significant temperature rise from 28.9 to 42.7 °C, while MnO2@PDA showed higher photothermal conversion efficiency, with the temperature rising from 28.9 to 53.1 °C in 10 min. MCPF demonstrated high phototoxicity on SMMC-7721 cells and had superior antitumor effects by combining PTT with PDT. A reduction in tumor volume was observed after administration of sorafenib, MCPF and MSCPF. The synergistic tumor-targeted and hypoxia-alleviated nanoplatform (MSCPF) that co-deliver sorafenib, Ce6, and MnO2 for combined chemo/PDT/PTT therapy proved an enhanced antitumor effect in HCC.	[144] (Wang, C. et al., 2022)
Supramolecular material Purp@COP	In vitro HCC cell line HepG2 was cultured for 24 h with Purp@COP, after which it was irradiated with an 808 nm NIR laser at a dose of 1 W/cm2 for 10 min.	The supramolecular material Purp@COP had double effects, both photodynamic and photothermal, with the suppression of the proliferation of cancer cells and their significant destruction. Purp@COP could be a PS with potential in the treatment of HCC.	[145] (Xu, W. et al., 2022)