Biocompatible Fe-Hematoporphyrin coordination nanoplatforms with efficient sonodynamic-chemo effects on deep-seated tumors

Abstract

Sonodynamic therapy (SDT) utilizing semiconductors or organic sonosensitizers has attracted increasing attention as a noninvasive treatment for deep-seated tumors, but its practical applications are still limited due to unsatisfactory therapeutical effects. To address the issue, we reported a metal-organic nanosonosensitizer by assembling clinical drug hematoporphyrin monomethyl ether (HMME) with Fe(III) ions through covalently coordination. The Fe-HMME coordination particles (FeCPs) had the average size of ~70 nm, and they were surface-modified with phospholipids to confer high hydrophilicity and stability. Upon ultrasound irradiation, they efficiently produced ¹O₂ to destroy cancer cells coated without or with tissue-barriers (1-3 cm). Importantly, the porous structure of FeCPs facilitated high loading capacity (31.3%) of anticancer drug doxorubicin (DOX), and the DOX@FeCPs exhibited pH-sensitive and ultrasound-enhanced releasing behavior that was favorable to the acidic microenvironment of tumors. When the lipids-coated FeCPs were intravenously injected into tumor-bearing mouse, they could passively accumulate within tumors, leading to the magnetic resonance imaging of tumors. Importantly, as deep-seated tumor model, tumors covered with barrier were exposed to ultrasound and thereafter their growth was significantly inhibited by SDT of FeCPs. The inhibition effects could be further enhanced by DOX@FeCPs due to the SDT-chemo combined therapy. Therefore, the DOX@FeCPs have achieved good therapeutical performances on deep-seated tumor and would supply some insights on the design of other metal-organic nanoplatforms.

Keywords: Deep-seated tumor; Drug delivery; Hematoporphyrin; Metal-organic coordination; Sonodynamic effect.