was that most nanoparticles do not have a sufficiently long blood half-life and cannot realize deep penetration in tumor tissue. Thus, recent progress in the development of strategies for mimicking or modulating cells offers a highly attractive alternative to drug delivery. [10-17] As natural immune cells and antigenpresenting cells, macrophages [18] have a long blood half-life and can specifically bind to tumor tissue. Therefore, applying macrophages in chemical drug delivery would lead to a significant increase in drug accumulation in tumors. Since macrophages can engulf foreign particles in nature, they can directly phagocytose drugs and then deliver drugs to tumors. [19] Thus, live macrophages may serve as drug carriers. To further increase the tumor-targeting ability of macrophages, they can be engineered with targeting ligands. [20] In addition, learning from red blood cell (RBC) membrane coating technology, [21-23] a macrophage cell membrane coating was developed and it resulted in enhanced tumor uptake of drugs. On the other hand, macrophages play an important role in modulating the tumor immune microenvironment. M1 macrophages inhibit tumor growth, while M2 macrophages promote tumor growth. Inhibition of M2 macrophages and repolarization of M2 macrophages to M1 macrophages are common strategies to treat solid tumors. Furthermore, since these macrophages express SIRPα on their surface, their phagocytic activity against CD47-expressing tumor cells is significantly affected by the CD47-SIRPα pathway. Therefore, blocking the CD47-SIRPα pathway can further enhance the anti-tumor efficacy of macrophages. Herein, to elucidate the importance of macrophages in tumor therapy (Figure 1), we will first discuss the role of macrophages in cancer immunotherapy, including the inhibition, depletion, and repolarization of tumor-associated macrophages (TAMs) and the blocking of the CD47-SIRPα pathway to enhance phagocytosis in tumor therapy. Then, based on the tumor targeting of M1 macrophages, we will discuss the applications of macrophages, macrophage-derived exosomes, and macrophage-coated NPs for drug delivery. We will thus offer a comprehensive understanding of functionalizing macrophages for tumor therapy. Macrophages play an important role in cancer development and metastasis. Proinflammatory M1 macrophages can phagocytose tumor cells, while antiinflammatory M2 macrophages such as tumor-associated macrophages (TAMs) promote tumor growth and invasion. Modulating the tumor immune microenvironment through engineering macrophages is efficacious in tumor therapy. M1 macrophages target cancerous cells and, therefore, can be used as drug carriers for tumor therapy. Herein, the strategies to engineer macrophages for cancer immunotherapy, such as inhibition of macrophage recruitment, depletion of TAMs, reprograming of TAMs, and blocking of the CD47-SIRPα pathway, are discussed. Further, the recent advances in drug delivery using M1 macrophages, macrophage-derived exosomes, and macrophage-membrane-coated nanoparticles are ela...

Pyroptosis is a lytic and inflammatory type of programmed cell death that is usually triggered by inflammasomes and executed by gasdermin proteins. The main characteristics of pyroptosis are cell swelling, membrane perforation, and the release of cell contents. In normal physiology, pyroptosis plays a critical role in host defense against pathogen infection. However, excessive pyroptosis may cause immoderate and continuous inflammatory responses that involves in the occurrence of inflammatory diseases. Attractively, as immunogenic cell death, pyroptosis can serve as a new strategy for cancer elimination by inducing pyroptotic cell death and activating intensely antitumor immunity. To make good use of this double-edged sword, the molecular mechanisms, and therapeutic implications of pyroptosis in related diseases need to be fully elucidated. In this review, we first systematically summarize the signaling pathways of pyroptosis and then present the available evidences indicating the role of pyroptosis in inflammatory diseases and cancer. Based on this, we focus on the recent progress in strategies that inhibit pyroptosis for treatment of inflammatory diseases, and those that induce pyroptosis for cancer therapy. Overall, this should shed light on future directions and provide novel ideas for using pyroptosis as a powerful tool to fight inflammatory diseases and cancer.

The etiology of cancer includes aberrant cellular homeostasis where a compromised RNA regulatory network is a prominent contributing factor. In particular, noncoding RNAs including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) were recently shown to play important roles in the initiation, progression, and metastasis of human cancers. Nonetheless, a mechanistic understanding of noncoding RNA functions in lung squamous cell carcinoma (LUSC) is lacking. To fill this critical gap in knowledge, we obtained mRNA, miRNA, and lncRNA expression data on patients with LUSC from the updated Cancer Genome Atlas (TCGA) database (2016). We successfully identified 3,366 mRNAs, 79 miRNAs, and 151 lncRNAs as key contributing factors of a high risk of LUSC. Furthermore, we hypothesized that the lncRNA–miRNA–mRNA regulatory axis positively correlates with LUSC and constructed a competitive endogenous RNA (ceRNA) network of LUSC by targeting interrelations with significantly aberrant expression data between miRNA and mRNA or lncRNA. Six ceRNAs (PLAU, miR-31-5p, miR-455-3p, FAM83A-AS1, MIR31HG, and MIR99AHG) significantly correlated with survival (P < 0.05). Finally, real-time quantitative PCR analysis showed that PLAU is significantly upregulated in SK-MES-1 cells compared with 16-BBE-T cells. Taken together, our findings represent new knowledge for a better understanding the ceRNA network in LUSC biology and pave the way to improved diagnosis and prognosis of LUSC.

Molecular imaging is very important in disease diagnosis and prognosis.