The hypoxic microenvironment in solid tumors severely limits the efficacy of photodynamic therapy (PDT). Therefore, the development of nanocarriers co-loaded with photosensitizers and oxygen, together with imaging guidance ability, is of great significance in cancer therapy. However, previously reported synthetic methods for these multi-functional probes are complicated, and the raw materials used are toxic.
Methods:
Herein, the human endogenous protein, hemoglobin (Hb), was used for the simultaneous biomimetic synthesis of Gd-based nanostructures and co-loading of Chlorine e6 (Ce6) and oxygen for alleviating the hypoxic environment of tumors and accomplishing magnetic resonance imaging (MRI)-guided enhanced PDT. The Gd@Hb
Ce6-PEG
nanoprobes were synthesized
via
a green and protein biomimetic approach. The physicochemical properties, including relaxivity, oxygen-carrying/release capability, and PDT efficacy of Gd@Hb
Ce6-PEG
, were measured
in vitro
and
in vivo
on tumor-bearing mice after intravenous injection. Morphologic and functional MRI were carried out to evaluate the efficacy of PDT.
Results:
The results demonstrated the successful synthesis of compact Gd@Hb
Ce6-PEG
nanostructures with desired multi-functionalities. Following treatment with the nanoparticles, the embedded MR moiety was effective in lighting tumor lesions and guiding therapy. The oxygen-carrying capability of Hb after biomimetic synthesis was confirmed by spectroscopic analysis and oxygen detector
in vitro
. Further, tumor oxygenation for alleviating tumor hypoxia
in vivo
after intravenous injection of Gd@Hb
Ce6-PEG
was verified by photoacoustic imaging and immunofluorescence staining. The potent treatment efficacy of PDT on early-stage was observed by the morphologic and functional MR imaging. Importantly, rapid renal clearance of the particles was observed after treatment.
Conclusion:
In this study, by using a human endogenous protein, we demonstrated the biomimetic synthesis of multi-functional nanoprobes for simultaneous tumor oxygenation and imaging-guided enhanced PDT. The therapeutic efficacy could be quantitatively confirmed at 6 h post PDT with diffusion-weighted imaging (DWI).