It is challenging and urgent in neurosurgery to improve therapeutic effect of the most common and lethal malignant glioma in central nervous system. The superadditive therapeutic effect of photothermal therapy and photodynamic therapy holds great promise. Herein, a highly efficient photothermal-photodynamic therapy nanoplatform was developed on the basis of Fe 3 O 4 -IR806 superparticles. The introduction of the near-infrared (NIR) dye IR806 and the fabrication of the self-assembled structure of the superparticles warrant 3.5 times increase in the photothermal conversion efficiency compared with the Fe 3 O 4 nanoparticles . The Fe 3 O 4 -IR806 superparticles generated reactive oxygen species (ROS) with the NIR light irradiation by virtue of the dye IR806. Both in vitro and in vivo experiments demonstrated that the Fe 3 O 4 -IR806 superparticles exhibited negligible toxicity. The Fe 3 O 4 -IR806 superparticles efficiently inhibited the cultured glioma cells via photothermal ablation and ROS cytotoxicity in vitro, as well as suppressed the bearing glioma growth in vivo with the NIR light induction. Our results highlight the promise of the Fe 3 O 4 -IR806 superparticles for improved photothermal-photodynamic therapy of cancer.
Focal therapy, or partial gland ablation, represents the middle ground between active surveillance and definitive treatment strategies against localized prostate cancer (PCa), among which the ultrasound- and light-mediated focal therapies are quite promising. Herein, for the first time in the literature, a novel polysaccharide-based nanoprodrug is fabricated for synergistic sonodynamic therapy and phototherapy against localized PCa. Specifically, the cyanine dye IR806 is conjugated to chondroitin sulfate (CS) via disulfide linkages to obtain CS-ss-IR806 (CSR) conjugates, which then self-assemble to form CSR nanoparticles (NPs) with properties of enhanced endocytosis, redox/hyaluronidase-responsiveness, and mitochondria-targeted ability. In contrast to free sensitizers, CSR NPs reveal dramatically enhanced water solubility, substantially lower dark toxicity, and superior biocompatibility. Encouragingly, favorable hyperthermia and high reactive oxygen species generation are observed on exposing CSR NPs to combined sono/photoirradiation. In a PCa tumor-bearing mice model, intratumoral injection with a markedly low dose of CSR NPs followed by dual-irradiation results in superior trimodal anticancer efficacy when compared with either monoirradiation strategy. Such synergistic antitumor efficacy is further demonstrated to be associated with the common and complementary mechanisms of sonotherapy and phototherapy. This work provides a promising approach as a next-generation focal therapy strategy against localized PCa.
Panpan Xue,Tingjie Bai,Huilan Zhuang,Angelo H. All,Shuangqian Yan,Xuemei Zeng
Stimulating the immunogenic cell death (ICD) by chemical and photothermal agents triggers antitumor immune responses to tumor treatments. However, the abnormal cholesterol accumulation in cancer cells promotes tumor survival and metastasis, while the high concentration of cholesterol in the tumor microenvironment will result in T exhaustion. Herein, a cholesterol-regulable nanoliposome (ictLipo) that encapsulated with IR806, tirapazamine, and cholesterol oxidase (ChOx) was fabricated to boost chemo/photothermal-activated ICD and antitumor immune responses. Specifically, the released ChOx oxidizes cholesterol, accompanied by oxygen consumption and ATP reduction. Whereupon, tumoral anabatic hypoxia activates the toxicity of tirapazamine while ATP reduction strengthens photothermal therapy of the IR806 by suppression of HSP70. We found that this interactive strategy evokes robust ICD and reverses T-cell exhaustion. When combined with the immune checkpoint blockade, ictLipo can efficiently restrain breast cancer metastasis in two tumor models. The interactive strategy sheds new light on the immunological facet of cholesterol metabolism and may provide a new therapeutic strategy against breast cancer.
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