Nanoscale hematoporphrin-based frameworks for photo-sono synergistic cancer therapy via utilizing Al(III) as metal nodes rather than heavy metals

Nanoscale metal-organic frameworks composed of heavy metal ions (such as Fe3+ and Cu2+) as metal nodes have been utilized for cancer therapy, but they suffer from serious quenching in fluorescence and photo-sono sensitization due to their paramagnetism and unsaturated 3d orbitals. To solve these problems, we synthesize nanoscale hematoporphrin-based frameworks with Al3+ ions as metal nodes (AlHFs) rather than heavy metals and achieve enhanced photo-sono therapy of malignant tumors. The hydrophilic AlHFs are prepared by first assembling hematoporphrin molecules and Al(III) trimers via covalent coordination and then surface-modifying them with 1,2-distearoyl-sn-glycero-3-phosphoethano lamine-N-(polyethylene glycol) (DSPE-PEG) molecules. Under excitation with 660 nm light or ultrasound, AlHFs-PEG can produce 3.6-fold or 2.8-fold more 1O2 species than the as-synthesized nanoscale Fehematoporphrin frameworks (FeHFs) because the Al3+ ions without 3d orbitals are not beneficial for energy transfer, while Fe3+ ions with unsaturated 3d orbitals and paramagnetism can cause significant energy transfer. AlHFs-PEG exhibits high biocompatibility and can be engulfed by cells to produce intracellular 1O2 for efficient destruction of cells. With the high biosafety and the photo-sono sensitization, the growth rate of tumors in mice with the AlHFs-PEG injection is significantly inhibited upon exposure to both light and ultrasound, showing higher therapeutic efficacy than photodynamic therapy or sonodynamic therapy alone. Therefore, the present work not only presents the preparation of AlHFs-PEG for tumor photo-sono therapy but also provides some insights for developing nanoscale frameworks with light metal ions as metal nodes. (c) 2022 Elsevier Inc. All rights reserved.

Automated summary

This study presents the synthesis of nanoscale hematoporphrin-based frameworks with Al3+ ions as metal nodes for enhanced photo-sono therapy of malignant tumors. The AlHFs-PEG exhibits high biocompatibility and can produce more 1O2 species than traditional metal-organic frameworks, inhibiting the growth rate of tumors in mice significantly when exposed to both light and ultrasound. This research provides insights for developing nanoscale frameworks with light metal ions as metal nodes.