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CRISPR system-assisted immunotherapy is an attractive option in cancer therapy. However, its efficacy is still less than expected due to the limitations in delivering the CRISPR system to target cancer cells. Here, we report a new CRISPR/Cas9 tumor-targeting delivery strategy based on bioorthogonal reactions for dual-targeted cancer immunotherapy. First, selective in vivo metabolic labeling of cancer and activation of the cGAS-STING pathway was achieved simultaneously through tumor microenvironment (TME)-biodegradable hollow manganese dioxide (H-MnO ) nano-platform. Subsequently, CRISPR/Cas9 system-loaded liposome was accumulated within the modified tumor tissue through in vivo click chemistry, resulting in the loss of protein tyrosine phosphatase N2 (PTPN2) and further sensitizing tumors to immunotherapy. Overall, our strategy provides a modular platform for precise gene editing in vivo and exhibits potent antitumor response by boosting innate and adaptive antitumor immunity.
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http://dx.doi.org/10.1002/anie.202306863 | DOI Listing |
Ann Hematol
September 2025
Excellence Center for Comprehensive Cancer (ECCCC), King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
Despite therapeutic advances, multiple myeloma (MM) remains incurable, especially in relapsed/refractory (R/R) cases. B-cell maturation antigen (BCMA) is a key target for novel immunotherapies, including chimeric antigen receptor T-cell (CAR-T) therapies and bispecific T-cell engagers (BiTEs), which vary in efficacy, toxicity, and accessibility. To compare the efficacy and safety of BCMA-directed CAR-T therapies and BiTEs in R/R MM through a systematic review and meta-analysis.
View Article and Find Full Text PDFEur J Nucl Med Mol Imaging
September 2025
Department of PET-CT/MRI, NHC Key Laboratory of Molecular Probe and Targeted Theranostics, Harbin Medical University Cancer Hospital, Harbin, 150081, Heilongjiang, China.
Objective: CXCR4 and integrin αβ play important roles in tumor biology and are highly expressed in multiple types of tumors. This study aimed to synthesize, preclinically evaluate, and clinically validate a novel dual-targeted PET imaging probe Ga-pentixafor-c(RGDfK) for its potential in imaging tumors.
Methods: The effects of Ga-pentixafor-c(RGDfK) on cell viability, targeting specificity, and affinity were assessed in the U87MG cells.
J Mater Chem B
September 2025
Faculty of Health Sciences, University of Macau, Macau SAR 999999, China.
Breast cancer is a global health challenge necessitating more precise and effective treatment strategies. In this study, we developed a novel drug-loaded therapeutic nanoplatform, OCPdots@CTe, which integrated near-infrared-II (NIR-II) window phototheranostic for targeted treatment of orthotopic breast tumors. The outer membrane vesicles (OMVs) can stimulate more immune responses based on precise targeting, while chelerythrine (CTe) can induce apoptosis by generating reactive oxygen species (ROS), thereby enhancing the therapeutic effect.
View Article and Find Full Text PDFCancer Med
August 2025
Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, China.
Background: De novo epidermal growth factor receptor-anaplastic lymphoma kinase (EGFR-ALK) and EGFR-ROS proto-oncogene 1 (EGFR-ROS1) co-mutations in non-small-cell lung cancer (NSCLC), conditions traditionally considered mutually exclusive. We present the first large‑scale analysis of their clinical and genomic profiles.
Methods: We identified 26 patients with EGFR-ALK (n = 20) or EGFR-ROS1 (n = 6) co-mutations from two institutions and compared them with cohorts of EGFR-only, ALK-only, ROS1-only, and non-co-mutated (NC) controls.
Int J Nanomedicine
August 2025
School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Zhongshan, 528458, People's Republic of China.
Purpose: This study designed a dopamine derivative integrating active targeting and pH-responsive borate ester bond-mediated passive targeting to construct drug delivery systems for tumor-targeted drug delivery, thus improving antitumor drug bioavailability and expanding the application of dopamine in drug delivery.
Methods: Nuclear magnetic resonance and Fourier transform infrared spectrometry were used to determine the structures of Man-PBA-DAO and Man-2PBA-DAO. Hydrodynamic diameter measurements confirmed the pH responsiveness of the targeting nanoparticles in different pH media over 12 hours.