Anticancer drug‐loaded nanoparticles have been explored extensively to decrease side effects while improving their therapeutic efficacy. However, due to the low drug loading content, premature drug release, nonstandardized carrier structure, and difficulty in predicting the fate of the carrier, only a few nanomedicines have been approved for clincial use. Herein, a carrier‐free nanoparticle based on the self‐assembly of the curcumin–erlotinib conjugate (EPC) is developed. The EPC nanoassembly exhibits more potent cell killing, better antimigration, and anti‐invasion effects for BxPC‐3 pancreatic cancer cells than the combination of free curcumin and erlotinib. Furthermore, benefiting from both passive and active tumor targeting effect, EPC nanoassembly can effectively accumulate in the tumor tissue in a xenograft pancreatic tumor mouse model. Consequently, EPC effectively reduces the growth of pancreatic tumors and extends the median survival time of the tumor‐bearing mice from 22 to 68 days. In addition, no systemic toxicity is detected in the mice receiving EPC treatment. Attributed to the uniformity of the curcumin–erlotinib conjugate and easiness of scaling up, it is expected that the EPC can be translated into a powerful tool in fighting against pancreatic cancer and other epidermal growth factor receptor positive cancers.

To date, more biodegradable polymers have been developed due to the growing recognition of the advantages of biodegradable and biocompatible polymers for biomedical applications. In this study, we introduce the synthesis and characterization of innovative polymers that incorporate biodegradable backbones composed of trimethylolpropane and adipic acid moieties and biocleavable side chains containing pyridyl disulfide groups. Notably, their synthesis is straightforward and catalyst-free under ambient conditions, minimizing potential toxicity and immune responses caused by catalyst residues in polymer materials. The new polymers have desired molecular weight (Mn: 18.8 kDa) with a narrow dispersion (PDI: 1.32) and offer complete biodegradability, biocompatibility, crosslinking capabilities, and opportunities for covalent chemical modifications. These features make them particularly suitable for use in biomedical materials and devices. Additionally, due to their unique properties, these polymers have been successfully formulated into polymeric gels and nanogels, which are biodegradable as well. Using a near-infrared fluorescent probe as a model cargo, we demonstrated the creation of a biosafe and sustainable nanogel system for agent delivery, with an average size of approximately 70 nm. In these nanogels, agent molecules are covalently attached to the scaffold, thereby avoiding uncontrolled premature release and burst release in the bloodstream and mitigating associated systemic toxicity and side effects. The nanogels can also be easily functionalized with targeting ligands for disease-specific delivery. These polymers induced minimal toxicity toward human cells and displayed excellent in vivo biocompatibility, highlighting the significant potential of their polymeric gels and nanogels for a broad spectrum of biomedical applications.

Tumor cells have high metabolic demands, leading to increased oxygen consumption and further exacerbating hypoxia, which has been regarded as a characteristic feature of solid tumors and plays a significant role in tumor growth, resistance to therapy, and overall treatment outcomes. Hypoxia-specific sensing probes are currently in urgent need to provide valuable information for tumor detection and monitoring. In this work, we developed a new near-IR fluorescence-emitting biosensor with a high fluorescence quantum yield for hypoxia detection in tumor tissues. In the presence of nitroreductase enzyme under tumor hypoxia, the nitro group of the biosensor molecule is converted into an amino group, and the resulting compound turns itself into a nonfluorescent dye through a self-immolating process, thus turning off the fluorescence emission of the biosensor. The fluorescence change of the biosensor in response to nitroreductase is sensitive and selective and is not influenced by the presence of other physiologically important species. In the in vitro and in vivo bioimaging experiments, the biosensor demonstrated high efficiency in detecting hypoxia and the capability of distinguishing solid tumors of different sizes, indicating its potential applications in tumor diagnosis and progression monitoring.