Image-guided surgery plays a crucial
role in realizing complete tumor removal, reducing postoperative recurrence
and increasing patient survival. However, imaging of tumor lesion
in the typical metabolic organs, e.g., kidney and liver, still has great challenges due to the intrinsic
nonspecific accumulation of imaging probes in those organs. Herein,
we report an in situ self-assembled near-infrared
(NIR) peptide probe with tumor-specific excretion-retarded (TER) effect
in tumor lesions, enabling high-performance imaging of human renal
cell carcinoma (RCC) and achieving complete tumor removal, ultimately
reducing postoperative recurrence. The NIR peptide probe first specifically
recognizes αvβ3 integrin overexpressed
in renal cancer cells, then is cleaved by MMP-2/9, which is up-regulated
in the tumor microenvironment. The probe residue spontaneously self-assembles
into nanofibers that exhibit an excretion-retarded effect in the kidney,
which contributes to a high signal-to-noise (S/N) ratio in orthotopic
RCC mice. Intriguingly, the TER effect also enables precisely identifying
eye-invisible tiny lesions (<1 mm), which contributes to complete
tumor removal and significantly reduces the postoperative recurrence
compared with traditional surgery. Finally, the TER strategy is successfully
employed in high-performance identification of human RCC in an ex vivo kidney perfusion model. Taken together, this NIR
peptide probe based on the TER strategy is a promising method for
detecting tumors in metabolic organs in diverse biomedical applications.
A novel ADAM17 inhibitor ZLDI-8 may be a potential chemosensitizer which sensitized CRC cells to 5-fluorouracil or irinotecan by reversing Notch and EMT pathways.
Tumor vasculature and cancer stem cells (CSCs) are two major hazards that accelerate this process. [2,3] Metastatic renal cancer is highly vascularized [4] and the abundant presence of CSCs Tumor vasculature and cancer stem cells (CSCs) accelerate the development of metastatic renal cancer. Dual inhibition of vascular endothelium and CSCs is still a challenge due to their different pathological features. Herein, a transformable dual-inhibition system (TDS) based on a self-assembly peptide is proposed to construct nanofibrous barriers on the cell membrane in situ, which contributes to 1) reducing endothelial permeability and angiogenesis; and 2) inhibiting stemness and metastasis of CSCs in renal cancer. TDS specifically targets overexpressed receptor CD105 that provides the possibility to modulate both endothelial cells and CSCs for cancer therapy. Subsequently, owing to ligand-receptor interaction-induced transformation, the nanofibers form a barrier on the cell membrane. For vascular endothelium, TDS reduces the vascular permeability to 67.0% ± 4.7% and decreases angiogenesis to 62.0% ± 4.0%, thereby preventing the renal cancer metastasis. For human-derived CSCs, TDS inhibits stemness by reducing endogenic miR-19b and its transportation via CSCs-derived exosomes, which increases PTEN expression and consequently suppresses CSCs-mediated metastasis. In patient-derived xenograft mice, TDS significantly inhibits the tumorigenesis and angiogenesis. It also reduces the metastatic nodules in lung 5.0-fold compared with the control group. TDS opens up a promising avenue for suppressing the metastasis of cancer.
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.
Microtubules play a crucial role in mitosis and are attractive targets for cancer therapy. Recently, we isolated viriditoxin, a cytotoxic and antibacterial compound, from a marine fungus Paecilomyces variotii. Viriditoxin has been reported to inhibit the polymerization of bacterial FtsZ, a tubulin-like GTPase that plays an essential role in bacterial cell division. Given the close structural homology between FtsZ and tubulin, we investigated the potential antimitotic effects of viriditoxin on human cancer cells. Viriditoxin, like paclitaxel, enhanced tubulin polymerization and stabilized microtubule polymers, thereby perturbing mitosis in the SK-OV-3 cell line. However, the morphology of the stabilized microtubules was different from that induced by paclitaxel, indicating subtle differences in the mode of action of these compounds. Microtubule dynamics are also essential in cell movement, and viriditoxin repressed migration and colony formation ability of SK-OV-3 cells. Based on these results, we propose that viriditoxin interrupts microtubule dynamics, thus leading to antimitotic and antimetastatic activities.
Missed or residual tumor burden results in high risk for bladder cancer relapse. However, existing fluorescent probes cannot meet the clinical needs because of inevitable photobleaching properties. Performance can be improved by maintaining intensive and sustained fluorescence signals via resistance to intraoperative saline flushing and intrinsic fluorescent decay, providing surgeons with sufficiently clear and high‐contrast surgical fields, avoiding residual tumors or missed diagnosis. This study designs and synthesizes a photostable cascade‐activatable peptide, a target reaction‐induced aggregation peptide (TRAP) system, which can construct polypeptide‐based nanofibers in situ on the cell membrane to achieve long‐term and stable imaging of bladder cancer. The probe has two parts: a target peptide (TP) targets CD44v6 to recognize bladder cancer cells, and a reaction‐induced aggregation peptide (RAP) is introduced, which effectively reacts with the TP via a click reaction to enhance the hydrophobicity of the whole molecule, assembling into nanofibers and further nanonetworks. Accordingly, probe retention on the cell membrane is prolonged, and photostability is significantly improved. Finally, the TRAP system is successfully employed in the high‐performance identification of human bladder cancer in ex vivo bladder tumor tissues. This cascade‐activatable peptide molecular probe based on the TRAP system enables efficient and stable imaging of bladder cancer.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.