EGFR is a potential therapeutic target for treating bladder cancer, but has not been approved for clinical use yet. Metformin is a widely used antidiabetic drug and has demonstrated interesting anticancer effects on various cancer models, alone or in combination with chemotherapeutic drugs. The efficacy of gefitinib, a well-known EGFR tyrosine kinase inhibitor, combined with metformin was assessed on bladder cancer and underlying mechanisms were explored. This drug combination induced a strong anti-proliferative and anti-colony forming effect and apoptosis in bladder cancer cell lines. Gefitinib suppressed EGFR signaling and inhibited phosphorylation of ERK and Akt. Metformin amplified this inhibitory effect and enhanced gefitinib-induced activation of AMPK signaling pathway. In vivo intravesical treatment of metformin and gefitinib on syngeneic orthotopic mice confirmed the significant inhibitory effect on bladder tumor growth. These two drugs may be an excellent combination for the treatment of bladder cancer through intravesical instillation.

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BackgroundThe main objective of this study was to develop novel BSA nanoparticles (BSA NPs) for improving the bioavailability of curcumin as an anticancer drug, and those BSA NPs were galactosylated for forming the curcumin-loaded galactosylated BSA nanoparticles (Gal-BSA-Cur NPs), thus enhancing their ability to target asialoglycoprotein receptor (ASGPR) overexpressed on hepatocellular carcinoma (HCC) cells.Materials and methodsGal-BSA-Cur NPs were prepared by the desolvation method and showed a spherical shape and well distribution with the average particle size of 116.24 nm.ResultsIn vitro drug release assay exhibited that Gal-BSA-Cur NPs had higher release rates and improved the curcumin solubility. Cell uptake studies confirmed that Gal-BSA-Cur NPs could selectively recognize receptors on the surface of HCC (HepG2) cells and improve internalization ability of drug compared with BSA NPs-loaded curcumin (BSA-Cur NPs), which might be due to high affinity to galactose. Further, the effects of Gal-BSA-Cur NPs were evaluated by cytotoxicity assay, crystal violet assay, cell apoptosis assay, and wound healing assay, respectively, which revealed that Gal-BSA-Cur NPs could inhibit HepG2 cells proliferation, induce cell apoptosis, and inhibit cell migration.ConclusionImmunofluorescence staining has proved that the effects of Gal-BSA-Cur NPs related to the suppression of the nuclear factor κB-p65 (NF-κB-p65) expression in HepG2 cell nucleus. Therefore, these results indicate that novel Gal-BSA-Cur NPs are potential candidates for targeted curcumin delivery to HCC cells.

Coordination states of metal-organic materials are known to dictate their physicochemical properties and applications in various fields. However, understanding and controlling coordination sites in metal-organic systems is challenging. Herein, we report the synthesis of site-selective coordinated metal-phenolic networks (MPNs) using flavonoids as coordination modulators. The site-selective coordination was systematically investigated experimentally and computationally using ligands with one, two, and multiple different coordination sites. Tuning the multimodal Fe coordination with catechol, carbonyl, and hydroxyl groups within the MPNs enabled the facile engineering of diverse physicochemical properties including size, selective permeability (20-2000 kDa), and pH-dependent degradability. This study expands our understanding of metal-phenolic chemistry and provides new routes for the rational design of structurally tailorable coordination-based materials.

Supramolecular assembly affords the development of a wide range of polypeptide-based biomaterials for drug delivery and nanomedicine. However, there remains a need to develop a platform for the rapid synthesis and study of diverse polypeptidebased materials without the need for employing complex chemistries. Herein, we develop a versatile strategy for creating polypeptide-based materials using polyphenols that display multiple synergistic cross-linking interactions with different polypeptide side groups. We evaluated the diverse interactions operating within these polypeptide−polyphenol networks via binding affinity, thermodynamics, and molecular docking studies and found that positively charged polypeptides (K a of ∼2 × 10 4 M −1 ) and polyproline (K a of ∼2 × 10 6 M −1 ) exhibited stronger interactions with polyphenols than other amino acids (K a of ∼2 × 10 3 M −1 ). Free-standing particles (capsules) were obtained from different homopolypeptides using a template-mediated strategy. The properties of the capsules varied with the homopolypeptide used, for example, positively charged polypeptides produced thicker shell walls (120 nm) with reduced permeability and involved multiple interactions (i.e., electrostatic and hydrogen), whereas uncharged polypeptides generated thinner (10 nm) and more permeable shell walls due to the dominant hydrophobic interactions. Polyarginine imparted cell penetration and endosomal escape properties to the polyarginine−tannic acid capsules, enabling enhanced delivery of the drug doxorubicin (2.5 times higher intracellular fluorescence after 24 h) and a corresponding higher cell death in vitro when compared with polyproline−tannic acid capsules. The ability to readily complex polyphenols with different types of polypeptides highlights that a wide range of functional materials can be generated for various applications.