Abstract
The drug resistance of hepatocellular carcinoma poses a great obstacle for chemotherapy as it severely undermines the clinical performance of common chemotherapeutics, and the implementation of nanotechnology-enabled combinational therapy offers new opportunities to circumvent this issue. Herein, an all-in-one hollow multi-component nanoformulation (aHNF) for hepatocellular carcinoma (HCC) treatment is reported, which could simultaneously load doxorubicin hydrochloride (Dox), chlorin e6 (Ce6) and manganic ions to realize Mn-amplified chemophototherapy. The loading strategy based on complexation effect and molecular selection establishes a simple yet effective platform for multi-component delivery via enhanced permeation and retention effect (EPR) and enables the sufficient release of photosensitizers to optimize the performance of photodynamic therapy (PDT). The co-delivery of Mn ions could elevate the cytotoxicity of both Dox and Ce6 via increasing the intracellular oxidative stress to damage cellular substructures and disrupt metabolic homeostasis. It also provides contrast for magnetic resonance imaging to guide the PDT treatment. This facile strategy allows to deliver multiple therapeutic modalities to hepatocellular carcinoma tissues, which then acts in synergy to overcome the treatment resistance of HCC and improves the antitumor activity.
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