Surface charge transition nano-theranostics based on ultra-small Fe3O4 nanoparticles for enhanced photodynamic and photothermal therapy against nasopharyngeal carcinoma

Abstract Platinum-based concurrent chemo-radiotherapy is the most common strategy for the treatment of Nasopharyngeal carcinoma. However, low efficacy and side effects are the two major problems associated with this approach. Therefore, it is urgent need to explore novel therapeutic modalities to meet clinically standards. Photothermal therapy (PTT) and photodynamic therapy (PDT) are non-invasive and light trigger modalities received great attention to overcome the limitations and significantly improved cancer therapy. Here, we developed acidity surface charge transformable nanocluster (NCs) composed of Indocyanine green (ICG), Fe3O4, and Palmitoyl ascorbic acid (PA) with pH-responsive PEG-b-PAEMA-PDMA for enhanced synergistic PDT/PTT. NCs has the neutral hydrophilic surface helps to prolong blood circulation and instantly transformed to positively charged surface at tumoral acidic pH (6.5), which promoted the cellular uptake. Under laser irradiation (808 nm, 1 W/cm2), NCs produced PTT effect, concurrently it converts singlet oxygen (1O2) into H2O2, which can be further involved in Fenton reaction and produce toxic hydroxyl radical (•OH) enhances therapy efficacy. In vitro experiments on HNE-1 cancer cells showed improved intracellular uptake of NCs at low pH and simultaneously induced higher cytotoxicity medicated by synergetic PDT/PTT effect. In vivo therapeutic study revealed that NCs treatment under laser irradiation showed superior inhibition of tumor growth in HNE-1 tumor bearing mice model. Taken together, the present findings suggest that NCs could be used as “all in one” nano theranostic agent for enhanced PDT/PTT of cancer therapy.