Extracellular matrix (ECM) is crucial in various biological functions during tumor progression, including induction of anoikis resistance and cell adhesion‐mediated drug resistance (CAM‐DR). Fibronectin (FN) is a vital ECM component with direct regulatory effects on ECM‐mediated anoikis resistance and CAM‐DR, making it an attractive and innovative therapeutic target for depriving ECM in tumor tissue. Herein, an ECM deprivation system (EDS) is developed based on FN targeting self‐assembly peptide for constructing nanofibers in the ECM of renal cell carcinoma (RCC), which contributes to: i) targeting and recognizing FN to form nanofibers for long‐term retention in ECM, ii) reversing anoikis resistance via arresting the FN signaling pathway, and iii) serving as a drug‐loading platform for sensitizing chemotherapy by ameliorating CAM‐DR. The results reveal that EDS significantly reverses anoikis resistance of RCC cells by inhibiting the phosphorylation of FAK, a positive regulator of the FN signaling pathway. Meanwhile, EDS serves as a chemotherapy‐sensitizer of cancer, exerting significant synergistic effects with doxorubicin (DOX). In vivo validation experiments show that EDS effectively suppresses metastasis and tumor growth with chemotherapy resistance. Collectively, the innovative EDS notably inhibits the tumor‐promoting effect of ECM and may provide a novel approach for suppressing ECM and enhancing chemo‐drug sensitivity.

Nearly half of pregnancies worldwide are unintended mainly due to failure of contraception, resulting in negative effects on women's health. Male contraception techniques, primarily condoms and vasectomy, play a crucial role in birth control, but cannot be both highly effective and reversible at the same time. Herein, an ultrasound (US)induced self-clearance hydrogel capable of real-time monitoring is utilized for in situ injection into the vas deferens, enabling effective contraception and noninvasive recanalization whenever needed. The hydrogel is composed of (i) sodium alginate (SA) conjugated with reactive oxygen species (ROS)-cleavable thioketal (SA-tK), (ii) titanium dioxide (TiO 2 ), which can generate a specific level of ROS after US treatment, and (iii) calcium chloride (CaCl 2 ), which triggers the formation of the hydrogel. For contraception, the above mixture agents are onetime injected into the vas deferens, which can transform from liquid to hydrogel within 160 s, thereby significantly physically blocking the vas deferens and inhibiting movability of sperm. When fertility is needed, a noninvasive remedial ultrasound can make TiO 2 generate ROS, which cleaves SA-tK to destroy the network of the hydrogel. Owing to the recanalization, the refertility rate is restored to 100%. Meanwhile, diagnostic ultrasound (D-US, 22 MHz) can monitor the occlusion and recanalization process in real-time. In summary, the proposed hydrogel contraception can be a reliable, safe, and reversible male contraceptive strategy that addresses an unmet need for men to control their fertility.

Encoded by the MEN1 gene, menin protein is a fusion protein that is essential for the oncogenic transformation of mixed-lineage leukemia (MLL) and leads to acute leukemia (AL). Therefore, accumulating evidence has demonstrated that inhibition of the high-affinity relationship between menin and mixed-lineage leukemia 1 (MLL1 and KMT2A) is an effective treatment for MLL-rearranged (MLL-r) leukemia in vitro and in vivo. Meanwhile, recent studies found that menin–MLL1 interaction inhibitors exhibited a firm tumor suppressive ability in specific cancer cells, such as prostate cancer, breast cancer, liver cancer, and lung cancer. Overall, it seems to serve as a novel therapeutic means for cancers. Herein, we review the recent progress in exploring the inhibitors of small molecule menin–MLL1 interactions. The molecular mechanisms of these inhibitors’ functions and their application prospects in the treatment of AL and cancers are explored.