Dual-modality imaging of peptide M2pep modified nanomicelle targeting tumor associated macrophages

Introduction: Tumor associated macrophages (TAMs) constitute a significant part in the tumor microenvironment and are classified into M1 and M2 macrophages. Among these, M2 TAMs can promote tumor progression and distal metastasis by degrading tumor extracellular matrix, promoting tumor angiogenesis, and recruiting immunosuppressive cells. Therefore, M2 TAMs have been considered a favorable target to cancer diagnosis and therapy. Herein, a nanomicelle targeting M2 TAMs was synthesized to co-deliver radionuclide and superparamagnetic iron (SPIO) to the tumor site for dual-modality imaging.

Methods: M2pep, a peptide ligand selectively binding to M2 TAMs, was coated on DSPE-PEG micelle via surface modification, which also conjugated radionuclides by a chelator DOTA and encapsulated the MRI contrast agent SPIO. The capability of nanomicelle to target M2 TAMs was assessed in vitro. We also investigated the imaging features by melanoma B16-F10 mouse models undergoing MRI and PET/CT imaging

Results: We chose ⁶⁸Ga as a radionuclide to conjugate DSPE-PEG nanomicelle encapsulated SPIO. Radiochemical purity over 90% was achieved. ⁶⁸Ga labelled nanomicelle with M2pep showed a higher cellular binding rate than those without M2pep. MRI findings showed accumulation of M2pep modified nanomicelle on the tumor site, and MRI signal decreased 23.93±2.71% and 30.23±8.87% at 1h and 4h post-injection, respectively. In Micro-PET/CT scanning, the uptake was deposited in the B16-F10 tumor at 1h post-injection 68Ga labelled nanomicelle with M2pep (Figure 1). The tumor/muscle ratio increased from 5.1 at 1h to 8.4 at 4h.

Conclusions: Our results confirm that M2pep modified nanomicelle provides a promising method for specific M2 TAMs dual-modality imaging. Further, we also can develop a M2pep modified therapeutic nanomicelle by using therapeutic radionuclides and drugs to replace ⁶⁸Ga and SPIO, which provides a potential strategy to inhibit tumor growth and metastasis.

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