Liposomal Glucose Oxidase for Enhanced Photothermal Therapy and Photodynamic Therapy against Breast Tumors

Organic near-infrared fluorescent dye mediated photothermal therapy (PTT) and photodynamic therapy (PDT)suffer from heat shock response, since, heat shock proteins (HSPs)are overexpressed and can repair the proteins damaged by PTTand PDT. Starvation therapy by glucose oxide (GOx) can inhibitthe heat shock response by limiting the energy supply. However,the delivery of sufficient and active GOx remains a challenge. Tosolve this problem, we utilize liposomes as drug carriers andprepare GOx loaded liposome (GOx@Lipo) with a high drugloading content (12.0%) and high enzymatic activity. Thesuccessful delivery of GOx shows excellent inhibition of HSPsand enhances PTT and PDT. Additionally, we apply the sameliposome formulation to load near-infrared dye 1,1 '-dioctadecyl-3,3,3 ',3 '-tetramethylindotricarbo cyanine iodide (DiR) and prepare DiR contained liposomes (DiR@Lipo) for PTT and PDT. Theliposomal formulation substantially enhances the PTT and PDT properties of DiR as well as the cellular uptake and tumoraccumulation. Finally, the combination therapy shows excellent tumor inhibition on 4T1 tumor-bearing mice. Interestingly, we alsofind that the starvation therapy can efficiently inhibit tumor metastasis, which is probably due to the immunogenic effect. Our workpresents a biocompatible and effective carrier for the combination of starvation therapy and phototherapy, emphasizing theimportance of auxiliary starvation therapy against tumor metastasis and offering important guidance for clinical PTT and PDT.