Nanozyme Hydrogels for Self-Augmented Sonodynamic/Photothermal Combination Therapy

Abstract

Sonosensitizer-mediated sonodynamic therapy (SDT) has emerged as a promising anti-tumor strategy. However, this strategy of continuous oxygen consumption further exacerbates the hypoxic tumor microenvironment, which limits its therapeutic efficacy. In this study, we designed a multifunctional hydrogel (PB+Ce6@Hy) that simultaneously co-delivers nanozyme prussian blue (PB) and sonosensitizer chlorin e6 (Ce6) for the realization of photothermal therapy (PTT) and enhanced SDT. When the hydrogel reaches the tumor tissue through local injection, the 808 nm laser can induce the hydrogel to warm up and soften, thereby triggering the release of PB and Ce6. PB can interact with endogenous H2O2in situ and generate sufficient oxygen to promote the Ce6-mediated SDT effect. Besides, due to the good encapsulation ability of the hydrogel, the nanomaterials can be released in a controlled manner by changing laser parameter, irradiation time, etc. The experimental results show that the PB+Ce6@Hy system we developed can generate a large amount of reactive oxygen species (ROS), which can be combined with the photothermal effect to kill tumor cells, as a result, tumor proliferation has been adequately inhibited. This combined PTT/SDT dynamic strategy provides a new perspective for Ce6-induced cancer therapy, showing great potential for clinical application.

The multifunctional Prussian blue/graphitic carbon nitride nanocomposites for fluorescence imaging-guided photothermal and photodynamic combination therapy

“…32 The fine energy spectrum of N 1s showed three binding energy peaks at 397.6 eV, 399.20 eV, and 400.9 eV, which were corresponding to Fe–N, N–(C) 3 and N–H bonds, respectively. 33 As shown in Fig. S1c,† the fine energy spectrum of O 1s had two absorption peaks at 531.9 eV and 533.4 eV, attributing to the CO and the binding energy of the C–O bond, respectively.…”

Nanozyme: a rising star for cancer therapy

“…58 Wang et al utilized a hydrogel to simultaneously deliver the Prussian blue (PB) nanozyme and organic sonosensitizer Ce6. 59 When the hydrogel reached the tumor site, PB and Ce6 were released, triggered by 808 nm laser irradiation. Due to the CAT-like activity of PB, sufficient oxygen was generated in situ to alleviate hypoxia and then promote Ce6-mediated SDT effect.…”

Tumor Microenvironment‐Related Sonodynamic Therapy Mediates Tumor Therapy

“…On the one hand, ST can reduce the internal glucose of tumors and reduce the energy source of tumor cells. CAT and CAT-like activity Au-rGO-ZnO@PVP, PMR, PEBVO@PEGNRS, Bac@ARS, SPNC, PB+Ce6@Hy, Ce6-MnO 2 -PVs, YHM, Cu 2 O-CNX@CeO 2 , CAT@HA-HMME NPs [51,53,54,156,157,158,159,160,161,162] Consumption of GSH AIMP [163] Catalytic CDT Mn 3 O 4 /OCN-PPIX@BSA, G-IrTe 2 [164,165] Suppress GSH generation BMP-BSO [166] Consumption of GSH, catalytic CDT UPFB, mZMD NCs, MO@FHO, AIPH@Cu-MOF [52,55,84,85] Consumption of GSH, catalytic ST CPCs@PEG [167] Reverse immunosuppression HABT-C@HA, MFC [168,169] Catalytic ST PPGE NCs [50] Consumption of GSH, catalytic CDT, catalytic ST MPG [170] pH-response DOX@PCN-224/Pt NPs [171] Carry oxygen Reverse immunosuppression TL@HPN(PAI/USI), DMXAAS [172,173] ICG-DOX NPs/PFH@SP94-Lip, SAFE [174,175] Autogeneration of oxygen Chl (MChl) [176] Reduce HIF-1𝛼 M@C [73] Reduce HIF-1𝛼 Relieve hypoxia P-BTO [71] IR780@INPS-CTX, IRP-NPs [177,178] Hypoxia-response ZTC, MCA, C-TiO 2 /TPZ@CM [77,179,180] Catalytic CDT Cu-MOF NPs [75] CAT activity hMVS [78] On the other hand, the produced H 2 O 2 can be used as the substrate of CDT and catalase to catalyze the formation of ROS and oxygen. [56]…”