Polyamidoamine dendrimer-mediated hydrogel for solubility enhancement and anti-cancer drug delivery.

The application of hydrogels for anti-cancer drug delivery has garnered considerable interest in the medical field. Current cancer treatment approaches, such as chemotherapy and radiation therapy, often induce severe side effects, causing significant distress and substantial health complications to patients. Hydrogels present an appealing solution as they can be precisely injected into specific sites within the body, facilitating the sustainable release of encapsulated drugs. This localized treatment approach holds great potential for reducing toxicity levels and improving drug delivery efficacy. In this study we developed a hydrogel delivery system containing polyamidoamine (PAMAM) dendrimer and polyethylene glycol (PEG) for solubility enhancement and sustained delivery of hydrophobic anti-cancer drugs. The three selected model drugs, e.g. silibinin, camptothecin, and methotrexate, possess limited aqueous solubility and thus face restricted application. In the presence of vinyl sulfone functionalized PAMAM dendrimer at 45 mg/mL concentration, drug solubility is increased by 37-fold, 4-fold, and 10-fold for silibinin, camptothecin, and methotrexate, respectively. By further crosslinking of the functionalized PAMAM dendrimer and thiolated PEG, we successfully developed a fast-crosslinking hydrogel capable of encapsulating a significant payload of solubilized cancer drugs for sustained release. In water, the drug encapsulated hydrogels release 30%-80% of their loads in 1-4 days. MTT assays of J82 and MCF7 cells with various doses of drug encapsulated hydrogels reveal that cytotoxicity is observed for all three drugs on both J82 and MCF7 cell lines after 48 h. Notably, camptothecin exhibits higher cytotoxicity to both cell lines than silibinin and methotrexate, achieving up to 95% cell death at experimental conditions, despite its lower solubility. Our experiments provide evidence that the PAMAM dendrimer-mediated hydrogel system significantly improves the solubility of hydrophobic drugs and facilitates their sustained release. These findings position the system as a promising platform for controlled delivery of hydrophobic drugs for intratumoral cancer treatment.

Significant Enhancement of Two-Photon Excited Fluorescence in Water-Soluble Triphenylamine-Based All-Organic Compounds.

Understanding water-soluble and environmentally friendly two-photon absorption (TPA) molecules benefits the design of superior organic complexes for biomedical, illumination, and display applications. In this work, we designed two triphenylamine-based all-organic compounds and explored the mechanism of enhanced TP fluorescence in water solutions for potential applications. Experimentally, we showed that adding protein into our TPA molecule solution can drastically boost the TP fluorescence. Numerical simulations reveal that the TPA molecules prefer to dock inside the protein complex. We hypothesize that the interaction between our triphenylamine-based all-organic compounds and water molecules lead to non-radiative decay processes, which prevent strong TP fluorescence in the water solution. Therefore, the protection by, for example, protein molecules from such interactions can be a universal strategy for superior functioning of organic TPA molecules. Further experiments and numerical simulations support our hypothesis. The present study may facilitate the design of superior water-soluble and environmentally friendly superior organic complexes.