Silmara C. Lazarini Frajácomo, Augusto Henrique [UNESP] Piva, Hernane da Silva Barud, Eliane Trovatti, Tamires de Souza Nossa, Bernardo Castro-Dominguez, Regina C. G. Frem, Bruna C. Lustri, Douglas H. Nakahata, Pedro P. Corbi, Wilton R. Lustri
Abstract Topical antimicrobial strategies that combine targeted drug delivery with selective cytotoxicity are critically needed for treating infected skin lesions, especially those complicated by multidrug-resistant bacteria. Here, we report the synthesis, characterization, and evaluation of a silver(I) complex with the sulfonamide probenecid (Ag–PROB) and its integration into a bacterial cellulose (BC) based composite with zeolitic imidazolate framework-8 (ZIF-8) for controlled release applications. We developed two delivery platforms, Ag–PROB@BC and Ag–PROB@BC/ZIF-8, with the latter incorporating the metal–organic framework, and assessed their antimicrobial and antitumor activities. Ag–PROB demonstrated potent, selective in vitro cytotoxicity against a panel of tumor cell lines, including pulmonary adenocarcinoma (A549, GI 50 = 35.77 μmol L −1 ) and murine melanoma (B16, GI 50 = 35.77 μmol L −1 ), with minimal effects on non-tumorigenic cells (e.g., HUVEC, GI 50 = 202.06 μmol L −1 and Hakata, GI = 249.16 μmol L −1 ). Both delivery systems showed sustained release in disk diffusion and Franz cell tests, with no observed DNA interaction, and in vivo toxicity was confirmed in Tenebrio molitor larvae. The Ag–PROB@BC/ZIF-8 composite displayed improved release profiles, providing a versatile platform for topical antimicrobial and antitumoral therapy. Our findings highlight a synergistic approach that combines metal-based therapeutics, bio-derived scaffolds, and ZIF-8 to create advanced multifunctional materials for skin cancer treatment.