Glycolysis in human cancers: Emphasis circRNA/glycolysis axis and nanoparticles in glycolysis regulation in cancer therapy

Alkhathami, Ali G.; Sahib, Ameer S.; Fayi, Majed Saad Al; Fadhil, Ali Abdulhussain; Jawad, Mohammed Abed; Shafik, Sahar Ahmad; Sultan, Safwan Jassim; Almulla, Abbas F.; Shen, Min

doi:10.1016/j.envres.2023.116007

Cited by 6 publications

(1 citation statement)

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“…In addition, interleukin-12-expressive plasmid was designed to express IL-12. Compared with those study for mRNA or circRNA delivery, 43,44 plasmid DNA is more stable and not easy to be degraded. Thus, the effect of DNA in tumor immunotherapy may be better than that of RNA to some extent.…”

Section: Discussionmentioning

confidence: 93%

IL-12-Overexpressed Nanoparticles Suppress the Proliferation of Melanoma Through Inducing ICD and Activating DC, CD8+ T, and CD4+ T Cells

Shen,

Peng,

Wang

et al. 2024

IJN

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The drug resistance and low response rates of immunotherapy limit its application. This study aimed to construct a new nanoparticle (CaCO 3 -polydopamine-polyethylenimine, CPP) to effectively deliver interleukin-12 (IL-12) and suppress cancer progress through immunotherapy. Methods: The size distribution of CPP and its zeta potential were measured using a Malvern Zetasizer Nano-ZS90. The morphology and electrophoresis tentative delay of CPP were analyzed using a JEM-1400 transmission electron microscope and an ultraviolet spectrophotometer, respectively. Cell proliferation was analyzed by MTT assay. Proteins were analyzed by Western blot. IL-12 and HMGB1 levels were estimated by ELISA kits. Live/dead staining assay was performed using a Calcein-AM/PI kit. ATP production was detected using an ATP assay kit. The xenografts in vivo were estimated in C57BL/6 mice. The levels of CD80 + /CD86 + , CD3 + / CD4 + and CD3 + /CD8 + were analyzed by flow cytometry. Results: CPP could effectively express EGFP or IL-12 and increase ROS levels. Laser treatment promoted CPP-IL-12 induced the number of dead or apoptotic cell. CPP-IL-12 and laser could further enhance CALR levels and extracellular HMGB1 levels and decrease intracellular HMGB1 and ATP levels, indicating that it may induce immunogenic cell death (ICD). The tumors and weights of xenografts in CPP-IL-12 or laser-treated mice were significantly reduced than in controls. The IL-12 expression, the CD80 + /CD86 + expression of DC from lymph glands, and the number of CD3 + /CD8 + T or CD3 + /CD4 + T cells from the spleen increased in CPP-IL-12-treated or laser-treated xenografts compared with controls. The levels of granzyme B, IFN-γ, and TNF-α in the serum of CPP-IL-12-treated mice increased. Interestingly, CPP-IL-12 treatment in local xenografts in the back of mice could effectively inhibit the growth of the distant untreated tumor. Conclusion:The novel CPP-IL-12 could overexpress IL-12 in melanoma cells and achieve immunotherapy to melanoma through inducing ICD, activating CD4 + T cell, and enhancing the function of tumor-reactive CD8 + T cells.

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Section: Discussionmentioning

confidence: 93%