Qifang Chen,Xianbin Ma,Li Xie,Wenjie Chen,Zhigang Xu,Erqun Song,Xiaokang Zhu,Yang Song
Ferroptosis therapy, which applies ferroptotic inducers to produce lethal lipid peroxidation and induce the death of tumor cells, is regarded as a promising therapeutic strategy for cancer treatment. However, there is still a challenge regarding how to increase reactive oxygen species (ROS) accumulation in the tumor microenvironment (TME) to enhance antitumor efficacy. Herein, we designed a nanosystem coated with the FDA approved poly(lactic-co-glycolic acid) (PLGA) containing ferrous ferric oxide (Fe3O4) and chlorin E6 (Ce6) for synergistic ferroptosis-photodynamic anticancer therapy. The Fe3O4-PLGA-Ce6 nanosystem can dissociate in the acidic TME to release ferrous/ferric ions and Ce6. Then, the Fenton reaction between the released ferrous/ferric ions and intracellular excess hydrogen peroxide can occur to produce hydroxyl radicals (˙OH) and induce tumor cell ferroptosis. The released Ce6 can increase the generation and accumulation of ROS under laser irradiation to offer photodynamic therapy, which can boost ferroptosis in 4T1 cells. Moreover, magnetic monodisperse Fe3O4 loading provides excellent T2-weighted magnetic resonance imaging (MRI) properties. The Fe3O4-PLGA-Ce6 nanosystem possesses MRI ability and highly efficient tumor suppression with high biocompatibility in vivo due to the synergism of photodynamic and ferroptosis antitumor therapies.
Wang Weicai,Liu Xiaofan,Ding Lairong,Jin Hyung Jong,Li Xuemei
Hypoxia is not only the reason of tumor metastasis but also enhances the spread of cancer cells from the original tumor site, which results in cancer recurrence. Herein, we developed a self-assembled RNA hydrogel that efficiently delivered synergistic DNA CpG and short hairpin RNA (shRNA) adjuvants, as well as MnO2 loaded-photodynamic agent chlorine e6 (MnO2@Ce6), and a chemotherapy drug doxorubicin (DOX) into MDA-MB-231cells. The RNA hydrogel consists of one tumour suppressor miRNA (miRNA-205) and one anti-metastatic miRNA (miRNA-182), both of which showed an outstanding effect in synergistically abrogating tumours. The hydrogel would be dissociated by endogenous Dicer enzyme to release loaded therapeutic molecules, and in the meantime induce decomposition of tumor endogenous H2O2 to relieve tumor hypoxia. As a result, a remarkable synergistic therapeutic effect is achieved through the combined chemo-photodynamic therapy, which simultaneously triggers a series of anti-tumor immune responses. Besides, the hydrogel as the carrier which modified aptamer to targeted MDA-MB-231 has the advantages of good biocompatibility and low cytotoxicity. This strategy could be implemented to design any other microRNA (miRNA) as the carrier, combined with other treatment methods to treat human cancer, thereby overcoming the limitations of current cancer therapies.
Melanoma treatment remains a challenge due to the inadequacy of existing clinical approaches and the difficulty of tissue regeneration. Recently, microneedles have been widely studied in tumor therapy and skin repair. Hence, a hyaluronic acid (HA)-based dual-functional hydrogel microneedle (MN) system was constructed to sequentially achieve tumor ablation and skin regeneration. Carbon nanotubes@calcium peroxide@tannic acid-Fe/chlorin e6 (CCa@TF/Ce6) nanomaterial was encapsulated in dissolvable polyvinyl alcohol/polyvinylpyrrolidone tips and accurately released to the tumor site to suppress melanoma via the photothermal and photodynamic therapies under the dual laser irradiation due to the generation of reactive oxygen species (ROS) and heat. Particularly, ROS and heat triggered immunogenic cell death, promoted dendritic cells maturation and reshaped the tumor-associated macrophage phenotype from the protumor M2 phenotype to the anti-tumor M1 phenotype, ultimately activating autoimmunity to eliminate the tumor. Following tumor ablation, the MN base accelerated skin regeneration owing to HB-PVA hydrogel through reducing oxidative stress, promoting cell proliferation and facilitating cell migration. Overall, the dual-functional hydrogel MN designed in this study, offers a new avenue for sequential melanoma combination treatment and skin regeneration.
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