Background: The exploitation of novel nanomaterials combining diagnostic and therapeutic functionalities within one single nanoplatform is challenging for tumor theranostics. Methods: We synthesized dendrimer-modified gold nanorods for combinational gene therapy and photothermal therapy (PTT) of colon cancer. Poly(amidoamine) dendrimers (PAMAM, G3) grafted gold nanorods were modified with GX1 peptide (a cyclic 7-mer peptide, CGNSNPKSC). The obtained Au NR@PAMAM-GX1 are proposed as a gene delivery vector to gene (FAM172A, regulates the proliferation and apoptosis of colon cancer cells) for the combination of photothermal therapy (PTT) and gene therapy of Colon cancer cells (HCT-8 cells). In addition, the CT imaging function of Au NR can provide imaging evidence for the diagnosis of colon cancer. Results: The results display that Au NR@PAMAM-GX1 can specifically deliver FAM172A to cancer cells with excellent transfection efficiency. The HCT-8 cells treated with the Au NR@PAMAM-GX1/FAM172A under laser irradiation have a viability of 20.45%, which is much lower than the survival rate of other single-mode PTT treatment or single-mode gene therapy. Furthermore, animal experiment results confirm that Au NR@PAMAM-GX1/FAM172A complexes can achieve tumor thermal imaging, targeted CT imaging, PTT and gene therapy after tail vein injection. Conclusion: Our findings demonstrate that the synthesized Au NR@PAMAM-GX1 offer a facile platform to exert antitumor and improve the diagnostic level of tumor.

Developing novel photosensitizers for deep tissue imaging and efficient photodynamic therapy (PDT) remains a challenge because of the poor water solubility, low reactive oxygen species (ROS) generation efficiency, serve dark cytotoxicity, and weak absorption in the NIR region of conventional photosensitizers. Herein, cyclometalated iridium (III) complexes (Ir) with aggregation-induced emission (AIE) feature, high photoinduced ROS generation efficiency, two-photon excitation, and mitochondria-targeting capability were designed and further encapsulated into biocompatible nanoparticles (NPs). The Ir-NPs can be used to disturb redox homeostasis in vitro, result in mitochondrial dysfunction and cell apoptosis. Importantly, in vivo experiments demonstrated that the Ir-NPs presented obviously tumor-targeting ability, excellent antitumor effect, and low systematic dark-toxicity. Moreover, the Ir-NPs could serve as a two-photon imaging agent for deep tissue bioimaging with a penetration depth of up to 300 μm. This work presents a promising strategy for designing a clinical application of multifunctional Ir-NPs toward bioimaging and PDT.

Background: Gut microbial metabolites are recognised as critical effector molecules that influence the development of colorectal cancer (CRC). Peptidoglycan fragments (PGFs) produced by microbiota play a crucial role in maintaining intestinal homeostasis, but their role in CRC remains unclear. Objective: Here, we aimed to explore the potential contribution of PGFs in intestinal tumourigenesis. Design: The relative abundance of peptidoglycan synthase and hydrolase genes was assessed by metagenomic analysis. Specific PGFs in the faeces and serum of CRC patients were quantified using targeted mass spectrometry. The effects of PGF on intestinal tumourigenesis were systematically evaluated using various murine models of CRC and organoids derived from CRC patients. Downstream molecular targets were screened and evaluated using proteome microarray, transcriptome sequencing and rescue assays. Results: Metagenomic analysis across seven independent cohorts (n=1121) revealed a comprehensive reduction in peptidoglycan synthase gene relative abundance in CRC patients. Targeted mass spectrometry identified significant depletion of a specific PGF, N-acetylmuramic acid (NAM) in CRC patients, which decreased as tumours progressed (p<0.001). NAM significantly inhibits intestinal tumourigenesis in various models, including Apc ^Min/+ , AOM/DSS-treated and MC38 tumour-bearing mice. Additionally, NAM inhibits the growth of patient-derived CRC organoids in a concentration-dependent manner. Mechanistically, NAM inhibits the activation of AKT1 by directly binding to it and blocking its phosphorylation, which is a partial mediator of NAM’s anticancer effects. Conclusion: The PGF NAM protects against intestinal tumourigenesis by targeting the AKT1 signalling pathway. NAM may serve as a novel potential preventive and therapeutic biomarker against CRC.

Background: Colorectal cancer (CRC) has a high worldwide incidence and mortality. Tumor metastasis is one of the primary reasons for the poor prognosis of CRC patients. However, the mechanism underlying CRC metastasis is still unclear. Myosin 1B (MYO1B) is important for cell migration and motility and is part of the myosin superfamily that contains various myosins. Studies of prostate, cervical, and head and neck cancer have revealed preliminary findings concerning the effect of MYO1B on tumor metastasis. However, the role of MYO1B in CRC metastasis, as well as its underlying mechanism, remains unknown. Methods: Quantitative real-time PCR and immunohistochemical staining methods were used to analyze the expression of MYO1B in human CRC and normal mucosa tissues. Lentivirus vector-based MYO1B oligonucleotides and short hairpin RNA (shRNA) were used to examine the functional relevance of MYO1B in CRC cells. Co-immunoprecipitation, western blotting, and immunofluorescence assays were used to investigate the underlying mechanism of MYO1B-mediated cell migration. Results: The expression of MYO1B was increased in most CRC tissues and was positively associated with a greater risk of tumor metastasis and poor prognosis for patients. MYO1B was significantly associated with the migration and invasion properties of CRC cells in vitro and in vivo. MYO1B promoted F-actin rearrangement through the ROCK2/LIMK/Cofilin axis by enhancing the activation of RhoA. MYO1B also promoted the assembly of focal adhesions by targeting RhoA. Conclusions: MYO1B plays a vital role in CRC metastasis by promoting the activation of RhoA. MYO1B may not only be a valid biomarker for predicting the risk of metastasis and poor prognosis in CRC but may also be a potential therapeutic target for patients with a high risk of tumor metastasis.