ABSTRACT
Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer, although it is limited by the low tumor delivery efficacy of anticancer drugs. Bacterial therapy is emerging for cancer treatment due to its high immune stimulation effect; however, excessively generated immunogenicity will cause serious inflammatory response syndrome. Here, we prepared cancer cell membrane-coated liposomal paclitaxel-loaded bacterial ghosts (LP@BG@CCM) by layer-by-layer encapsulation for the treatment of metastatic lung cancer. The preparation processes were simple, only involving film formation, electroporation, and pore extrusion. LP@BG@CCM owned much higher 4T1 cancer cell toxicity than LP@BG due to its faster fusion with cancer cells. In the 4T1 breast cancer metastatic lung cancer mouse models, the remarkably higher lung targeting of intravenously injected LP@BG@CCM was observed with the almost normalized lung appearance, the reduced lung weight, the clear lung tissue structure, and the enhanced cancer cell apoptosis compared to its precursors. Moreover, several major immune factors were improved after administration of LP@BG@CCM, including the CD4+/CD8a+ T cells in the spleen and the TNF-α, IFN-γ, and IL-4 in the lung. LP@BG@CCM exhibits the optimal synergistic chemo-immunotherapy, which is a promising medication for the treatment of metastatic lung cancer.
ABSTRACT
BACKGROUND:Photothermal therapy is a novel tumor treatment strategy that uses photothermal agents to transform light energy into heat energy to accomplish non-invasive tumor ablation.The rise of photothermal therapy and nanotechnology has provided a new perspective on breast cancer treatment.OBJECTIVE:To prepare a new type of near-infrared biomimetic nanoprobe that has been modified by breast cancer cell membrane,to investigate the effect of near-infrared fluorescence/ultrasound imaging in vitro,and to observe its targeting ability and photothermal therapy effect on homologous tumor cells in vitro.METHODS:Organic small molecule ITIC-4CI with A-D-A structure was used as photothermal agents;polylactic acid/glycolic acid copolymer as nanocarrier;4T1 cell membrane of mouse breast cancer cells as a surface modifier of nanoparticles;perfluorohexane(PFH)was loaded.A novel near-infrared biomimetic nanoprobe(4T1m/ITIC-4CI/PFH)was prepared by the double emulsion evaporation method and sonication method.The basic characterization of the nanoprobe and the homologous targeting ability were detected.The photothermal properties and photothermal stability of the probe were investigated,and the near-infrared fluorescence/ultrasound imaging effect of the probe under laser irradiation was observed.The CCK-8 assay and calcein/propidium iodide staining were used to assess the efficacy of photothermal therapy.RESULTS AND CONCLUSION:(1)The prepared 4T1m/ITIC-4CI/PFH nanoprobes had uniform size,high stability,and an average particle size of(92.7±2.3)nm.The probe's protein composition was identical to that of the 4T1 cell membrane.The nanoprobe's ability to target homologous 4T1 cells was validated by an in vitro cell uptake assay.(2)The nanoprobe had a red-shift absorption spectrum and tail emission extending to the near-infrared-Ⅱ,which emitted a bright near-infrared-Ⅱ fluorescence signal under laser irradiation.(3)After laser irradiation,the nanoprobe 4T1m/ITIC-4CI/PFH could be turned into microbubbles and enhanced ultrasound imaging.The results of CCK-8 assay and calcein/propidium iodide staining showed that the nanoprobe 4T1m/ITIC-4CI/PFH had an obvious photothermal killing effect on 4T1 cells.(4)The results show that the nanoprobe 4T1m/ITIC-4CI/PFH has the ability to target homologous tumors and enhance near-infrared-Ⅱ fluorescence imaging/ultrasound imaging and photothermal therapy effects.
ABSTRACT
In the development of chemo-immunotherapy, many efforts have been focusing on designing suitable carriers to realize the co-delivery of chemotherapeutic and immunotherapeutic with different physicochemical properties and mechanisms of action. Besides, rapid drug release at the tumor site with minimal drug degradation is also essential to facilitate the antitumor effect in a short time. Here, we reported a cancer cell membrane-coated pH-responsive nanogel (NG@M) to co-deliver chemotherapeutic paclitaxel (PTX) and immunotherapeutic agent interleukin-2 (IL-2) under mild conditions for combinational treatment of triple-negative breast cancer. In the designed nanogels, the synthetic copolymer PDEA-co-HP-β-cyclodextrin-co-Pluronic F127 and charge reversible polymer dimethylmaleic anhydride-modified polyethyleneimine endowed nanogels with excellent drug-loading capacity and rapid responsive drug-releasing behavior under acidic tumor microenvironment. Benefited from tumor homologous targeting capacity, NG@M exhibited 4.59-fold higher accumulation at the homologous tumor site than heterologous cancer cell membrane-coated NG. Rapidly released PTX and IL-2 enhanced the maturation of dendritic cells and quickly activated the antitumor immune response in situ, followed by prompted infiltration of immune effector cells. By the combined chemo-immunotherapy, enhanced antitumor effect and efficient pulmonary metastasis inhibition were achieved with a prolonged median survival rate (39 days).
ABSTRACT
OBJECTIVE: To investigate a biomimetic nano-targeted drug modifide by cancer cell membrane and to discuss its efficiency in breast cancer. METHODS: The lac-DOX/DOX was prepared by filming-rehydration method, and the 4T1 cell membrane was extracted at the same time. The lac-DOX /DOX@4T1m was prepared by sonication method.. The morphology of lac-DOX /DOX@4T1m was observed by a transmission electron microscopy. The protein on 4T1 cell membrane was analyzed by gel electrophoresis. The targeting of drugs to homologous cancer cells in vivo and in vitro were evaluated by cell uptake experiments and imaging experiments of small animals. 4T1 tumor-bearing Balb/c mice were built, the anti-tumor efficacy and biosafety of lac-DOX/ DOX@4t1m were evaluated. RESULTS: The prepared lac-DOX /DOX@4T1m have a regular spherical shape with an average particle diameter of (204.8±13.0)nm, and the protein entirety remained on the cell membrane. The results of cell uptake experiments and in vivo imaging experiments of mice showed that lac-DOX/DOX@4T1m can target 4T1 cells. Antitumor test results showed that lac-DOX/ DOX@4T1m could inhibit tumor growth more effectively and significantly reduce the damage to liver function. CONCLUSION: In this study, a bionic nano-drug is successfully prepared, which improve the tumor targeting and therapeutic effect, reduce the toxic effects of adriamycin, and improve the drug safety.