Mechanosynthesis of Terpene Oligosulfides and Nanogold for Anticancer Therapy

June 22, 2026

Terpenes and carotenoids recovered from agro-industrial residues constitute attractive bio-based precursors for sustainable anticancer materials. This thesis explored the solvent-free mechanochemical inverse vulcanisation of lycopene and β-carotene with elemental sulphur, evaluated the anticancer potential of limonene-derived oligosulfides in non-small cell lung cancer models, and investigated gold nanoparticles (AuNPs) as delivery vehicles for the sulphur-rich products obtained. Optimised conditions maintained internal temperatures below 40 °C (lycopene:S₈ 1:3, 500 rpm, 60 min; β-carotene:S₈ 1:2, 600 rpm, 120 min). Chemical transformation of both carotenoids was confirmed by TLC, FTIR, and NMR spectroscopy, demonstrating disruption of the polyene backbone and formation of new sulphur-containing species. AuNPs were prepared by conventional citrate reduction and by a mechanochemical route. The conventional synthesis produced predominantly spherical particles with modal diameters of 24–53 nm, with 18-crown-6 improving size distribution homogeneity. Mechanochemically synthesised AuNPs exhibited broader size distributions (33–118 nm), partially refined by centrifugation, with 1-hour milling providing the best long-term colloidal stability. Limonene-derived oligosulfides induced concentration- and time-dependent cytotoxicity in H292 and PC-9 cells, with LC₅₀ values decreasing from 63.3 to 51.4 μM and from 62.8 to 38.9 μM, respectively, between 24 and 72 hours. The greater sensitivity of PC-9 cells, harbouring an EGFR exon 19 deletion, is consistent with increased vulnerability to disulfide stress and interpreted within the framework of disulfidptosis. This work establishes mechanochemical inverse vulcanisation as a green and viable strategy for producing sulphur-enriched terpene derivatives with demonstrated biological activity in lung cancer models, identifying AuNPs as promising delivery carriers.

Authors in the community:

• 

  J

  Jorge Miguel de Melo Gomes

  ist138143

Supervisors of this institution:

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  V

  Vasco Daniel Bigas Bonifácio

  ist90152

industrial-biotechnology - Industrial Biotechnology

eng - English

Instituto Superior Técnico