Cobalt Doped in Zn-MOF-5 Nanoparticles to Regulate Tumor Microenvironment for Tumor Chemo/Chemodynamic Therapy.

Metal-organic frameworks are often used as a chemotherapeutic drug carrier due to their diverse metal sites and good acid degradation ability. Herein Co-doped Zn-MOF-5 nanoparticles with a high Co doping rate of 60% were synthesized for chemo-chemodynamic synergistic therapy of tumor. Co ions can mediate chemodynamic therapy through Fenton-like reaction and regulate the tumor microenvironment by consuming the reduced glutathione. The CoZn-MOF-5 shows high drug loading capacity with doxorubicin loading rate of 72.8%. The CoZn-MOF-5@PEG@DOX nanodrugs has a strong killing effect on 4T1 cancer cells, suggesting the chemo-chemodynamic synergistic effect on tumor therapy.

Biomimetic Cucurbitacin B-Polydopamine Nanoparticles for Synergistic Chemo-Photothermal Therapy of Breast Cancer.

Breast cancer is the most common malignant tumor in women. Researchers have found that the combined use of multiple methods to treat tumors is a promising strategy. Here, we have developed a biomimetic nano-platform PDA@MB for tumor targeted photothermal therapy (PTT) combined with chemotherapy. The 4T1 cell membrane loaded with cucurbitacin B (CuB) was used to coat polydopamine (PDA) nanoparticles, which gave PDA@MB nanoparticles the ability to target tumors and escape immune cells from phagocytosis. PDA@MB showed excellent photothermal performance including high photothermal conversion efficiency and photostability, and exhibited outstanding in vitro PTT effect under NIR laser irradiation. The high temperature ruptured the PDA@MB membrane to release CuB, which changed the tumor hypoxic environment, down-regulated the FAK/MMP signaling pathway, and significantly inhibited the metastasis and proliferation of tumor cells. The results of in vivo experiments indicated that the tumor growth of the 4T1 mouse tumor model was significantly inhibited. Additionally, toxicity studies showed that PDA@MB had good biocompatibility and safety. In conclusion, this study provides a promising chemo-photothermal therapy (CPT) nano-platform for precise and effective breast cancer therapy.

Cantharidin-loaded biomimetic MOF nanoparticle cascade to enhance the Fenton reaction based on amplified photothermal therapy.

The treatment efficiency of the Fenton reaction is expected to be greatly restricted due to problems such as inefficient delivery of Fenton catalysis, limited H2O2 concentration and uneven tumour tissue. Accurate photothermal therapy (PTT) could improve the efficiency of Fenton catalysis to some extent by raising the temperature. However, the heat shock response (HSR) of tumour cells caused by PTT and Fenton reaction would attenuate the treatment effect. In this study, we developed an iron ions-mediated Fenton reaction combined with a PTT treatment platform based on a metal-organic framework, i.e., PPy-CTD@MIL-100@MPCM nanoparticles (PCMM NPs), and further explored the inhibitory effect of PCMM NPs on the heat shock response (HSR). PCMM NPs could accumulate in tumour tissue via the coated macrophage cell membranes (MPCMs) to target inflammatory tissues. The photothermal effect of polypyrrole (PPy) accelerated the release of cantharidin (CTD) and iron ions loaded in the PCMM NPs. CTD, as an HSR inhibitor, could inhibit this response of tumour cells and improve the effect of PTT. Meanwhile, the heat generated during the PTT process could improve the efficiency of the Fenton reaction. This study suggested that PCMM NPs could serve as a combined treatment platform to enhance the Fenton reaction based on amplified photothermal therapy.

Cantharidin-loaded functional mesoporous titanium peroxide nanoparticles for non-small cell lung cancer targeted chemotherapy combined with high effective photodynamic therapy.

BACKGROUND: Although photodynamic therapy (PDT) has emerged as a potential alternative to conventional chemotherapy, the low reactive oxygen species (ROS) yield of the photosensitizer such as TiO2 nanoparticles has limited its application. In addition, it is difficult to achieve effective tumor treatment with a single tumor therapy. METHODS: We used TiOx nanocomposite (YSA-PEG-TiOX ) instead of TiO2 as a photosensitizer to solve the problem of insufficient ROS generation in PDT. Benefiting from the desired mesoporous structure of TiOx, Cantharidin (CTD), one of the active components of mylabris, is loaded into TiOx for targeted combination of chemotherapy and PDT. The cellular uptake in human non-small cell lung carcinoma cell line (A549) and human normal breast cell line (MCF 10A) was evaluated by confocal microscopy. in vitro cytotoxicity was evaluated using Cell Counting Kit-8 assay. The ROS was detected via a chemical probe DCFH-DA and the photodynamic treatment effect of YSA-PEG-TiOx was further evaluated by a living-dead staining. The cell apoptosis was detected by the flow cytometry. RESULTS: Our findings showed that the modification of YSA peptide improved the cytotoxicity of YSA-PEG-TiOX /CTD to EphA2 overexpressing A549 non-small cell lung cancer (NSCLC) than non-YSA modified counterparts. In addition, TiOx generated adequate ROS under X-ray irradiation to further kill cancer cells. Flow analysis results also proved the superiority of this combined treatment. CONCLUSIONS: YSA-PEG-TiOX nanoparticles could significantly increase ROS production under X-ray exposure and provide a new drug delivery nanocarrier for CTD in combination with PDT to achieve effective NSCLC treatment.