Abstract
Carbonic anhydrase IX (CA IX), over-expressed on cancer cells, catalyzes CO2 to bicarbonate and protons, contributing to the acidic extracellular pH (pHe), which enhances the multidrug resistance of tumor cells. Therefore, alleviating tumor acidosis would greatly improve the outcome of chemotherapy. This work fabricates acetazolamide (ACE)-loaded pH-responsive nanoparticles (ACE-NPs), which are quickly disintegrated in an acidic solution (pH 6.8), resulting in a quick release of ACE from these NPs to inhibit the expression of CA IX, thus up-regulating the pHe value. These ACE-NPs have no obvious in vitro cytotoxicity and in vivo studies confirm the accumulation of ACE-NPs in tumor tissue. In addition, mice treated with ACE and paclitaxel (PTX) co-loaded NPs show a smaller tumor size and a higher survival rate when compared to that of mice treated with ACE- or PTX-loaded NPs. This work reveals that simultaneous delivery of ACE and chemotherapy agents to tumor tissue can up-regulate the acidic pHe value, consequently enhancing the anti-tumor ability of chemotherapy medicine. These findings open a new window for enhancing the anti-tumor ability of traditional chemotherapy in clinic.
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