Correction to "Diterpenoid Tanshinones Can Inhibit Lung Cancer Progression by Improving the Tumor Microenvironment and Downregulation of NF-κB Expression".

[This corrects the article DOI: 10.1021/acsomega.3c09667.].

Diterpenoid Tanshinones Can Inhibit Lung Cancer Progression by Improving the Tumor Microenvironment and Downregulation of NF-κB Expression.

Diterpenoid tanshinones (DTs) are a bioactive fraction extracted from Salvia miltiorrhiza. High-performance liquid chromatography analysis revealed the presence of four compounds, namely, tanshinone IIA, tanshinone I, cryptotanshinone, and dihydrotanshinone. In this study, we aimed to propose a possible mechanism for the anti-lung cancer effect of DT. To do so, we utilized a lung cancer nude mice model and a lung cancer cell line (PC9) to investigate the effect of DT on lung cancer. We employed immunohistochemistry, enzyme-linked immunosorbent assay, hematoxylin and eosin staining, and immunofluorescence to analyze the pharmacological role of DT in the inhibition of lung cancer growth. The results showed that DT inhibited tumor growth, induced apoptosis in the nude mice model, and reduced inflammatory cell infiltration. Additionally, DT inhibited PC9 lung cancer cells, growth, proliferation, and migration. The mechanism of action of DT involves not only directly inhibiting cell proliferation and migration but also improving the tumor microenvironment. DT significantly increased the expression of important intestinal gap junction proteins, such as zonula occludens 1 (ZO-1) and occludin I. This upregulation contributes to the reinforcement of the intestinal mucosal barrier, thereby reducing the paracellular transport of lipopolysaccharides (LPS) through the intestine. Consequently, the decreased LPS levels lead to the inhibition of NF-κB expression and downregulation of macrophage polarization, as indicated by the decreased expression of CD68. In conclusion, this study has confirmed that DT has anti-lung cancer properties by improving the inflammatory tumor microenvironment via regulating macrophage polarization and inhibiting LPS-associated immune response. These results provide new insights into the mechanism of DT action against lung cancer.

The Landscape of Nucleic-Acid-Based Aptamers for Treatment of Hematologic Malignancies: Challenges and Future Directions.

Hematologic malignancies, including leukemia, lymphoma, myeloproliferative disorder and plasma cell neoplasia, are genetically heterogeneous and characterized by an uncontrolled proliferation of their corresponding cell lineages in the bone marrow, peripheral blood, tissues or plasma. Although there are many types of therapeutic drugs (e.g., TKIs, chemotherapy drugs) available for treatment of different malignancies, the relapse, drug resistance and severe side effects due to the lack of selectivity seriously limit their clinical application. Currently, although antibody-drug conjugates have been well established as able to target and deliver highly potent chemotherapy agents into cancer cells for the reduction of damage to healthy cells and have achieved success in leukemia treatment, they still also have shortcomings such as high cost, high immunogenicity and low stability. Aptamers are ssDNA or RNA oligonucleotides that can also precisely deliver therapeutic agents into cancer cells through specifically recognizing the membrane protein on cancer cells, which is similar to the capabilities of monoclonal antibodies. Aptamers exhibit higher binding affinity, lower immunogenicity and higher thermal stability than antibodies. Therefore, in this review we comprehensively describe recent advances in the development of aptamer-drug conjugates (ApDCs) with cytotoxic payload through chemical linkers or direct incorporation, as well as further introduce the latest promising aptamers-based therapeutic strategies such as aptamer-T cell therapy and aptamer-PROTAC, clarifying their bright application, development direction and challenges in the treatment of hematologic malignancies.

Aptamers: an emerging navigation tool of therapeutic agents for targeted cancer therapy.

Chemotherapeutic agents have been used for the treatment of numerous cancers, but due to poor selectivity and severe systemic side effects, their clinical application is limited. Single-stranded DNA (ssDNA) or RNA aptamers could conjugate with highly toxic chemotherapy drugs, toxins, therapeutic RNAs or other molecules as novel aptamer-drug conjugates (ApDCs), which are capable of significantly improving the therapeutic efficacy and reducing the systemic toxicity of drugs and have great potential in clinics for targeted cancer therapy. In this review, we have comprehensively discussed and summarized the current advances in the screening approaches of aptamers for specific cancer biomarker targeting and development of the aptamer-drug conjugate strategy for targeted drug delivery. Moreover, considering the huge progress in artificial intelligence (AI) for protein and RNA structure predictions, automatic design of aptamers using deep/machine learning techniques could be a powerful approach for rapid and precise construction of biopharmaceutics (i.e., ApDCs) for application in cancer targeted therapy.