Yolk-shell polyphosphazenes nanotheranostics for multimodal imaging guided effective phototherapy

A critical issue of photodynamic therapy (PDT) is the hypoxia feature in tumor microenvironment and the PDT-caused continuous oxygen consumption, which suppresses the effect of tumor treatment. Though the perfluorocarbon-based microbubbles with high oxygen affinity have been utilized to supply endogenous oxygen to improve PDT, some risks are wished to be addressed including oxygen leakage and storage issues. Herein, perfluorohexane (PFH) and Fe 3 O 4 nanoparticles were encapsulated in biocompatible polyphosphazenes (PPZ) and polydopamine (PDA) shells were further grown to prevent the leakage of PFH. After loading chlorine e6 (Ce6) and modifying with polyethylene glycol (PEG), a multimodal nanotheranostic (PFH–Fe 3 O 4 @PPZ@PDA-PEG-Ce6) were successfully constructed for ultrasonic (US), magnetic resonance (MR) and fluorescence imaging guided photothermal therapy (PTT) and enhanced PDT. PFH can not only bind and delivery oxygen but also be used as contrast agent for US imaging. While PDA is a frequently used PTT agent and Ce6 is PDT agent as well as fluorescent agent. The yolk-shell nanoplatform showed good biocompatibility, biostability and well cellular uptake. Importantly, strengthened PDT efficiency has also been greatly improved due to high oxygen-rich PFH. Furthermore, the nanoplatform efficiently generated hyperthermia to kill tumor upon 808 nm illumination. Remarkably, the PTT/enhanced PDT combination therapy can be realized under the guidance of US/MR/fluorescence imaging. This nanoplatform could dramatically inhibit tumor growth by PTT and improved PDT, demonstrating great promising for multimodal imaging guided phototherapy. Perfluorohexane (PFH) and Fe 3 O 4 nanoparticles were encapsulated in biocompatible polyphosphazenes (PPZ), and the PTT/enhanced PDT combination therapy can be realized under the guidance of US/MR/fluorescence imaging. • Perfluorohexane (PFH) and Fe 3 O 4 nanoparticles were encapsulated in biocompatible polyphosphazenes. • Strengthened PDT efficiency has also been greatly improved due to high oxygen-rich PFH. • The PTT/enhanced PDT combination therapy can be realized under the guidance of US/MR/fluorescence imaging.