Photosensitizer-based photodynamic therapy (PDT) has attracted great attention in cancer treatment. However, achieving efficient delivery of photosensitizers is still a great challenge for their clinical applications. The photosensitizer-encapsulating delivery nanosystem usually suffers from poor stability, complex preparation process and low drug loading. Herein, we utilize a surfactant-like chemotherapeutic agent, mitoxantrone (MTX), as a nanocarrier to deliver a photosensitizer pyropheophorbide a (PPa) for antitumor therapy. MTX consists of aromatic rings (hydrophobic part) and two amino-groups and two hydroxyl-groups (hydrophilic part) with planar structure, which could interact with PPa via π-π stacking, hydrophobic interactions, intermolecular hydrogen bonding and electrostatic interactions. This system (PPa@MTX) spontaneously forms near-spherical nanostructures (∼150 nm), has a high loading capacity for PPa (56.5%) and exhibits a pH-responsive drug release manner in vitro. In vivo antitumor efficacy evaluations show that the pegylated PPa@MTX nanosystem has increased accumulation in tumor tissues and enhanced antitumor efficacy in female BALB/c mice bearing murine mammary carcinoma (4T1) tumor cells, compared to free PPa. Employing the surfactant-like drug as nanocarriers, our results show that the "drug-delivering-drug" strategy is a good foundation for the development of novel PDT-based drug delivery system against cancer.
Keywords: Drug-delivering-drug; Mitoxantrone; Photodynamic therapy; Pyropheophorbide a.
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