BMC Gastroenterology, Год журнала: 2024, Номер 24(1)
Опубликована: Дек. 30, 2024
Gastric cancer (GC) remains one of the predominant malignant tumors within digestive tract, yet its underlying biological mechanisms remain elusive. The primary objective this study is to delineate causal relationship between circulating metabolites and GC.
Язык: Английский
Nano Letters, Год журнала: 2025, Номер unknown
Опубликована: Март 8, 2025
Photodynamic therapy has become a promising treatment modality against many diseases, but its dilemma―the intrinsic hypoxia of solid tumors and the high oxygen dependence for generation cytotoxic species―has seriously hampered practical translation. Herein binary supramolecular nanocarrier, which is composed fluorocarbon chain-appended β-cyclodextrin as an carrier adamantane-grafted hyaluronic acid cell-targeting agent, can deliver different types photosensitizers by multiple noncovalent interactions. Superior to alkylated counterpart, fluorinated amphiphilic spontaneously form nanoparticulate assembly exhibit oxygen-enrichment performance. The obtained nanoassembly alleviate in tumor microenvironment enhance efficacy photodynamic therapy. Remarkable phototoxicity minimal dark toxicity are observed cancer cells, meanwhile, preferential accumulation significant ablation realized tumor-bearing mice. To be envisioned, this capable efficiently carrying explored universal platform precise phototherapeutics.
Язык: Английский
Процитировано
0
Advanced Science, Год журнала: 2025, Номер unknown
Опубликована: Апрель 3, 2025
Recently, targeted protein degradation (TPD) strategies have emerged as a promising solution to tackle undruggable proteins. While most TPD target intracellular proteins, limited options exist for targeting extracellular or membrane Herein, cancer specific carbonic anhydrase IX (CAIX)-targeting supramolecular nanofibrous lysosome-targeting chimeras (Supra-LYTAC) is reported. Two self-assembling amphiphilic peptides are synthesized: one that interacts with the of interest (POI), and another mediates lysosomal endocytosis by cancer-specific enzyme. Notably, these two co-assemble into nanofibers capable cells in spatiotemporal manner. Through dynamic multivalent binding, ternary complex form (supramolecular chimeric nanostructure; CAIX-nanofiber-POI), which undergoes internalization lysosomes where POI degraded through catalytic activity. This study demonstrates potential approaches expand scope LYTAC technology, offering new opportunities designing future.
Язык: Английский
Процитировано
0
The Journal of Organic Chemistry, Год журнала: 2025, Номер unknown
Опубликована: Апрель 17, 2025
The development of water-soluble multicharged macrocycles has opened promising pathways in biomedical applications, enabling selective molecular recognition for therapeutic and diagnostic uses. Yet, traditional polyanionic polycationic receptors often face performance limitations under realistic operating conditions. A major drawback is the natural tendency these polycharged hosts to experience increasing screening effects as concentration rises due self-ion pairing phenomena, which can reduce binding efficiency by several orders magnitude. These issues are further intensified when polyionic used high-salinity environments, typically replicate physiological settings, where abundance ions introduces additional that diminish supramolecular affinity a wide range guests. This study presents new approach leverages zwitterionic synthetic with rationally engineered architectures overcome challenges. By incorporation specific structural features, eliminated, effectively making host no longer controlling factor thermodynamics complexation process. Additionally, dual-charged achieve self-contained stabilization, naturally shielding sites from external ion interference Furthermore, ability encapsulate guests, challenging task strong solvation molecules aqueous solution, adds significant value functional versatility macrocycles. Altogether, findings represent advancement design stable adaptable receptor systems complex environments.
Язык: Английский
Процитировано
0
Journal of the American Chemical Society, Год журнала: 2024, Номер unknown
Опубликована: Дек. 26, 2024
Triple-negative breast cancer (TNBC) poses significant treatment challenges due to its high metastasis, heterogeneity, and poor biomarker expression. The N-terminus of an octapeptide NAPVSIPQ (NAP) was covalently coupled a carboxylic acid derivative Ru(2,2′-bipy)32+ (Rubpy) synthesize N-stapled short peptide-Rubpy conjugate (Ru-NAP). This photosensitizer (PS) utilized treat TNBC through microtubule (MT) targeted chemotherapy photodynamic therapy (PDT). Ru-NAP formed more elaborate molecular aggregates with fibrillar morphology as compared NAP. A much higher binding affinity over NAP toward β-tubulin (KRu-NAP: (6.8 ± 0.55) × 106 M–1; KNAP: (8.2 1.1) 104 M–1) observed stronger electrostatic interactions between the MT average linear charge density ∼85 e/nm cationic Rubpy part Ru-NAP. also supported by docking, simulation, appropriate imaging studies. promoted serum stability, specific E-site βIII-tubulin followed disruption network, effective singlet oxygen generation in cells (MDA-MB-231), causing cell cycle arrest G2/M phase triggering apoptosis. Remarkably, MDA-MB-231 were sensitive noncancerous human embryonic kidney (HEK293 cells) when exposed light (LightIC50Ru-NAP[HEK293]: 17.2 2.5 μM, LightIC50Ru-NAP[MDA-MB-231]: 32.5 7.8 nM, DarkIC50Ru-NAP[HEK293]: > 80 DarkIC50Ru-NAP[MDA-MB-231]: 2.9 0.5 μM). effectively inhibited tumor growth xenograft models nude mice. Our findings provide strong evidence that has potential therapeutic role treatment.
Язык: Английский
Процитировано
0
BMC Gastroenterology, Год журнала: 2024, Номер 24(1)
Опубликована: Дек. 30, 2024
Gastric cancer (GC) remains one of the predominant malignant tumors within digestive tract, yet its underlying biological mechanisms remain elusive. The primary objective this study is to delineate causal relationship between circulating metabolites and GC.
Язык: Английский
Процитировано
0