pH- and NIR light responsive nanocarriers for combination treatment of chemotherapy and photodynamic therapy†
The side effects of antitumor drugs and low treatment efficacy are two major challenges of current chemotherapy. To address these issues, we developed a new kind of smart nanocarriers that combine pH-responsive chemotherapy and near-infrared (NIR) light triggered photodynamic therapy. These nanocarriers were based on upconversion nanoparticle (UCN)-loaded folate-conjugated polymeric lipid vesicles (UFPLVs). Merocyanine 540 (MC540), as a photosensitizer, was loaded in the UFPLVs; doxorubicin hydrochloride (DOX), as an antitumor drug, was conjugated to the surfaces of UFPLVs by pH-sensitive hydrazone bonds. The newly developed MC540&DOX–UFPLVs had a nanosized structure with targeting ligand modification, so they had the potential to accumulate into tumor sites via a combination of passive and active targeting effects. An in vitro singlet oxygen test showed that the nanocarriers can generate cytotoxic singlet oxygen successfully under the irradiation of NIR light. In vitro DOX release profiles demonstrated that the nanocarriers can achieve a pH-triggered drug release. It has been demonstrated by a cellular uptake study that the nanocarriers can efficiently deliver drugs and photosensitizers into tumor cells. In vitro and in vivo combination treatments evidenced the high antitumor effects of MC540&DOX–UFPLVs under NIR light irradiation. These results suggest that the MC540&DOX–UFPLVs may be promising nanocarriers for tumor combination therapy applications.