Background/Objectives: Crickets are recognized as an alternative source of chitosan. This study aimed to assess the potential of cricket-derived chitosan as a natural source to develop chitosan nanoparticles (CNPs). Methods: Chitosan were isolated from different cricket species, including Gryllus bimaculatus, Teleogryllus mitratus, and Acheta domesticus. The isolated chitosan were characterized by their functional groups, crystallographic and thermal properties, molecular structure, morphology, water solubility, molecular weight, binding capacity, irritation potential, and cytotoxicity in comparison to commercial shrimp-based chitosan. CNPs were developed through an ionotropic gelation method, followed by the evaluation of particle size, polydispersity index (PDI), and zeta potential. Results: The findings of this study indicate that chitosan can be successfully isolated from the three cricket species, with yields ranging from 4.35% to 5.22% w/w of the dried material. The characteristics of cricket-based chitosan were similar to those of commercial chitosan, except that the cricket-based chitosan displayed a higher crystallinity and a lower molecular weight. Additionally, CPNs were successfully produced from cricket-based chitosan using sodium citrate as a crosslinking agent. All cricket-based chitosan exhibited no irritation or cytotoxicity. Chitosan derived from A. domesticus however was found to be the most suitable to develop CPNs, as it produced the smallest particle size (522.0 ± 12.1 nm) with a comparatively narrow PDI (0.388 ± 0.026) and an acceptable positive zeta potential (34.2 ± 4.4 mV). Conclusions: Cricket-derived chitosan compares favorably with crustacean-derived chitosan and showed potential for a range of applications, including the use as a nanocosmeceutical delivery system in topical and cosmetic formulations.

Chalcones from medicinal plants are attractive starting points for anticancer lead discovery, and this study aimed to improve the anti-NSCLC potential of 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone (DMC) from Syzygium nervosum through targeted structural modification and mechanistic computational analysis. Air-dried seeds were extracted with CH₂Cl₂, DMC was purified by silica gel chromatography and crystallization, and its structure was confirmed by HRMS, FTIR and NMR; 4′-O-derivatization with meta– or para–[(bromomethyl)phenyl]methyl groups afforded derivatives 2a and 2b (89–92% yield). Antiproliferative activity and cytotoxicity were evaluated by MTT assay in NSCLC cell lines (A549, NCI-H460) and normal lung fibroblasts (MRC-5) with osimertinib as a reference. Derivatives 2a and 2b showed enhanced activity against NCI-H460 (IC₅₀ = 7.97 ± 0.62 µM and 7.91 ± 2.77 µM) while remaining weak against A549, and they were less cytotoxic to MRC-5 (IC₅₀ ≥ 50 µM and 16.08 ± 0.45 µM) than osimertinib (IC₅₀ = 3.43 ± 0.35 µM). DFT/MEP analyses, docking to wild-type EGFR (1M17; redocking RMSD 1.228 Å), and 500 ns × 3 replica MD simulations supported improved EGFR binding stability for 2a/2b, with MM/GBSA indicating favorable binding free energies (−28.78 ± 6.11 and −21.99 ± 9.39 kcal/mol). Overall, 4′-O-functionalization of DMC generated lead derivatives with improved in vitro activity in NCI-H460 and computationally supported target–ligand stabilization.