| Texto completo | |
| Autor(es): |
Gundel, Samanta da Silva
;
Dallemole, Danieli Rosane
;
Guterres, Silvia Staniscuaski
;
Lenz, Guido
;
Pohlmann, Adriana Raffin
Número total de Autores: 5
|
| Tipo de documento: | Artigo Científico |
| Fonte: | JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY; v. 114, p. 14-pg., 2025-10-09. |
| Resumo | |
Lung cancer is the leading cause of cancer mortality worldwide. Major challenges in its treatment include resistance to chemotherapy drugs and severe systemic side effects, which limit the effectiveness of conventional therapies. This study investigates the development of nanocapsules loaded with etoposide (NC ETO) and functionalized with different ligands targeting Epidermal Growth Factor Receptors (EGFR), aiming for a more effective and selective therapy for lung cancer. NC ETO was prepared using the preformed polymer interfacial deposition method. Surface modification was obtained through chitosan coating (NC ETO-CS), and by organometallic complexation using Gold-III as metal ion, and functionalization with different ligands (Amphiregulin - AREG, Epidermal Growth Factor - EGF, Erlotinib - ERL, or Transforming Growth Factor alpha - TGF alpha). The functionalized nanocapsules exhibited unimodal size distributions (similar to 175 nm), a positive zeta potential (+12 mV), high etoposide content (0.35 mg mL(-1)), and high encapsulation efficiency (similar to 90 %). We evaluated cell proliferation and cellular uptake of healthy cells (pulmonary fibroblasts, MRC5) and lung adenocarcinoma cells (A549), and observed greater tumor selectivity after functionalization of the nanocapsule surface, with emphasis on NC ETO-CS-AREG and NC ETO-CS-EGF, which presented cytotoxicity selectivity approximately 7x higher and uptake selectivity approximately 1.5x higher. Etoposide nanoencapsulation resulted in a remarkable long-term increase in the proportion of pre-senescent and senescent cells (>60 %) during a 20-day experiment with 53BP1-transduced A549 cells. The functionalized nanocapsules showed more pronounced effects on inducing senescence and nuclear damage compared to NC ETO-CS, with NC ETO-CS-AREG exhibiting the highest indices of senescence (>70 %) and nuclear damage (>40 %). These results highlight the superiority of nanoencapsulation, particularly with functionalization, in enhancing the cytotoxic effects and senescence induction of etoposide in lung cancer cells. (AU) | |
| Processo FAPESP: | 14/50928-2 - INCT 2014: Nanotecnologia Farmacêutica: uma abordagem transdisciplinar |
| Beneficiário: | Maria Vitória Lopes Badra Bentley |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |