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The targeted delivery of chemotherapeutic drugs is amajor challenge in the clinical treatment of cancer.Herein, we constructed amultifunctional DNAnanoplatform as aversatile carrier of the highly potent platinum-based DNAintercalator, 56MESS.I no ur rational design, 56MESS was efficiently loaded into the double-bundle DNAt etrahedron through intercalation with the DNAd uplex. With the integration of an anobody that both targets and blocks epidermal growth factor receptor (EGFR), the DNAn anocarriers exhibit excellent selectivity for cells with elevated EGFR expression (a common biomarker related to tumor formation) and combined tumor therapyw ithout obvious systemic toxicity. This DNA-based platinum-drug delivery system provides apromising strategy for the treatment of tumors.

Highlights d Periostin deficiency inhibits colorectal tumor formation in mice d Periostin is mainly secreted by fibroblasts to promote tumor cell proliferation d Periostin promotes YAP/TAZ nuclear localization and IL-6 expression in tumor cells d IL-6 promotes fibroblast activation and periostin expression during tumorigenesis

Precisely assembled DNA nanostructures are promising candidates for the delivery of biomolecule-based therapeutics. Herein, we introduce a facile strategy for the construction of a branched DNA-based nanoplatform for codelivery of gene editing (sgRNA/Cas9, targeting DNA in the nucleus) and gene silencing (antisense, targeting mRNA in the cytoplasm) components for synergistic tumor therapy in vitro and in vivo. In our design, the branched DNA structure can efficiently load a sgRNA/Cas9/antisense complex targeting a tumor-associated gene, PLK1, through DNA self-assembly. With the incorporation of an active targeting aptamer and an endosomal escape peptide by host–guest interaction, the biocompatible DNA nanoplatform demonstrates efficient inhibition of tumor growth without apparent systemic toxicity. This multifunctional DNA nanocarrier provides a new strategy for the development of gene therapeutics.

Delivery of proteins to carry out desired biological functions is a direct approach for disease treatment. However, protein therapy is still facing challenges due to low delivery efficiency, poor targeting during trafficking, insufficient therapeutic efficacy, and possible toxicity induced by carriers. Here, we present a novel delivery platform based on DNA origami nanostructure that enables tumor cell transportation of active proteins for cancer therapy. In our design, cytotoxic protein ribonuclease (RNase) A molecules are organized on the rectangular DNA origami nanosheets, which work as nanovehicles to deliver RNase A molecules into the cytoplasm and execute their cell-killing function inside the tumor cells. Cancer cell-targeting aptamers are also integrated onto the DNA origami-based nanoplatform to enhance its targeting effect. This DNA origamiprotein coassembling strategy can be further developed to transport other functional proteins and therapeutic components simultaneously for synergistic effects and be adapted for integrated diagnostics and therapeutics.

Periostin actively contributes to tissue injury, fibrosis, atherosclerosis, and inflammatory diseases; however, its role in hepatic fibrosis is unclear. Herein, we revealed that periostin expression was significantly up-regulated in carbon tetrachloride- and bile duct ligation-induced mice with acute and chronic liver fibrosis. Deficiency in periostin abrogated the development of liver fibrosis in mice. Carbon tetrachloride treatment significantly increased α-smooth muscle actin, fibronectin, and collagen I levels in wild-type mice, which were unaffected in periostin-knockout mice. Periostin-deficient mice showed a significantly reduced area of collagen deposition and decreased levels of serum alanine aminotransferase and aspartate aminotransferase compared with wild-type mice after 2 weeks of carbon tetrachloride administration. Chemokine ligand 2, IL-6, IL-1β, tumor necrosis factor-α, and tissue inhibitor of metalloproteinases 1 mRNA levels were significantly lower in periostin-deficient mice than in wild-type mice after carbon tetrachloride treatment. Periostin colocalized with hepatic stellate cell-derived collagen I and α-smooth muscle actin in mouse acute and chronic fibrotic liver tissues. Transforming growth factor (TGF)-β1 markedly induced periostin expression in primary mouse hepatic stellate cells. Periostin-deficient mice showed significantly lower levels of TGF-β1 and TGF-β2 compared with wild-type mice after carbon tetrachloride treatment. High levels of periostin in patients with acute or chronic hepatitis correlated with TGF-β1 and TGF-β2 expression in serum from patients with hepatitis. Data indicate that periostin is a novel mediator of hepatic fibrosis development.

Tumor cells actively contribute to constructing their own microenvironment during tumorigenesis and tumor progression. The tumor microenvironment contains multiple types of stromal cells that work together with the extracellular matrix and local and systemic factors to coordinately contribute to tumor initiation and progression. Tumor cells and their stromal compartments acquire many genetic and/or epigenetic alternations to facilitate tumor growth and metastasis. The cancer stem cell (CSC) concept has been widely applied to interpreting tumor initiation, growth, metastasis, dormancy and relapse. CSCs have differentiation abilities to generate the original lineage cells that are similar to their normal stem cell counterparts. Interestingly, recent evidence demonstrates that CSCs also have the potential to transdifferentiate into vascular endothelial cells and pericytes, indicating that CSCs can transdifferentiate into other lineage cells for promoting tumor growth and metastasis in some tissue contexts instead of only recruiting stromal cells from local or distant tissues. Although the transdifferentiation of CSCs into tumor stromal cells provides a new dimension that explains tumor heterogeneity, many aspects of CSC transdifferentiation remain elusive. In this review, we summarize the multi-lineage differentiation and transdifferentiation potentials of CSCs as well as discuss their potential contributions to tumor heterogeneity and tumor microenvironment in tumor progression.