# Cellular Entry, Cytotoxicityicity, and Antifungal Activity of Newly Synthesized Dendrimers
## 1 Introduction  
Modern nanomaterials exhibit a broad spectrum of applications, ranging from biosensors to nutritional supplements [1, 2]. Dendrimer-based compounds and their derivativeshave gained increasing attention in the fields of medicine and pharmaceuticals, including targeted drug delivery, diagnostic imaging, gene therapy, and the development of antibacterial, antiviral, and anti-amyloid agents [3; 4; 5; 6]. Dendrimers are polymeric molecules with highly branched structures. They are composed of layers of dendrons (concentrated branched entities) from a central initiating core, and each subsequent layer is referred to as a generation (G) [7]. The selection of a core directly determines the structure of the dendrimer, including the total number of branches of the dendron, the size, and the number of cavities within the dendrimer. Dendrimers possess nanoscale dimensions, ranging from 1 to 100 nm, and exhibit a low polydispersity index, which enhances their ability to penetrate cell membranes and facilitates efficient cellular uptake [8]. The size, topology, and viscosity of dendrimers can be precisely controlled during their synthesis, making them highly versatile nanostructures. Currently, approximately 100 distinct dendrimer families have been identified, each defined by its core structure, such as carbon, nitrogen, or phosphorus, as well as its branching units and terminal functional groups, which can carry a variety of charges [9]. This structural complexity enables dendrimers to exhibit an effect closely resembling the polyvalent interactions commonly observed in biological systems [10]. Such molecular diversity allows for extensive chemical modifications and broadens their potential applications, ranging from drug delivery and gene therapy to antimicrobial and antiviral therapies [11; 12; 13; 14]. Many dendrimers are known to exhibit antimicrobial activity. The antimicrobial effect of dendrimers depends on their concentration and surface charge: cationic dendrimers tend to exhibit stronger effects compared to anionic and neutral ones due to the electrostatic interactions with the negatively charged microbial membranes, the progressive permeabilization of the bacterial membranes, and the subsequent disruption of membrane integrity [15; 16]. The two newly synthesized dendrimers composed of 4-dimethylamino-1,8-naphthalimide (DAB) and 3-bromo-4-dimethylamino-1,8-naphthalimide (DAB-Br), used in our work, have demonstrated antibacterial and antiviral potential in a previous study [17]. In parallel, the growing resistance of pathogenic fungi continues to pose a serious public health challenge. Compared to antibacterial agents, the number of antifungal compounds under development or approved for clinical use remains disproportionately low. Fungal diseases currently affect nearly a quarter of the global population, with superficial infections of the skin, hair, nails, and mucous membranes representing the most prevalent mycoses. These infections, impacting approximately 20-25% of people worldwide, are predominantly caused by dermatophytes belonging to the genera _Trichoptyton_, _Microsporum_, _Alternaria_, _Aspergillus_, and _Candida_ spp., particularly _C. albicans_. Given these challenges, there is an urgent need to explore alternative therapeutic strategies and novel compounds with innovative mechanisms of action and new therapeutic applications. Dendrimers emerge as promising candidates in this context as they offer significant potential both as efficient carriers of antifungal agents and as active therapeutic agents [18]. Cell membrane integrity is a vital feature when evaluating the mode of entry and potential cytotoxicity of dendrimers, which can be specifically engineered to efficiently penetrate cellular membranes [19; 20; 21; 22; 23]. The lipid bilayer of the cell membrane is a dynamic, two-dimensional fluid, with its most essential properties being fluidity and molecular order. These characteristics are fundamental for maintaining membrane integrity, permeability, and membrane adaptation.