Impact of nanoplatforms allied to nitric oxide and chemotherapeutics on cytotoxicity and sensitization of resistant tumor cells

• Grant number: 20/03646-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: November 01, 2020
• End date: May 31, 2025
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Physical-Chemistry
• Principal Investigator: Amedea Barozzi Seabra
• Grantee: Joana Claudio Pieretti
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Santo André , SP, Brazil
• Associated scholarship(s): 21/12705-5 - Assessment of the antitumoral properties of nitric oxide and chemotherapeutic releasing nanoparticles in liver cancer cells, BE.EP.DR

Abstract

Currently, Cancer represents the second disease with the highest mortality rate worldwide, demonstrating challenges regarding the diagnosis and the treatment. In recent decades, Cancer treatments have improved, but they still face difficulties related to high biodistribution, due to the non-specificity, and also the growing tumor resistance to these conventional treatments. In this scenario, nanotechnology has gained space in the field of Medicine by enabling the design of materials that provide efficient, targeted applications with minimal side effects. This area has grown exponentially worldwide, with notable financial investment which have translated into the commercialization of more than 100 FDA approved products with applications in NanoMedicine. Among several nanoparticles with applications in this area, porous nanoparticles, such as zinc oxides and silicon (ZnO and SiO2), consist of a potential strategy for an efficient delivery of drugs with reduced side effects. A few years ago, the use of nanotechnology in Cancer was based only on a targeted treatment using drug-loaded nanoparticles. However, it has been increasing a simultaneous multi-drug delivery strategy, in order to sensitize tumor cells, especially cells resistant to current therapeutics. In this sense, a combination of chemotherapeutics with nanoparticles functionalized with S-nitrosochitosan, chemically modified chitosan polymer for nitric oxide (NO) release, consists of an innovative strategy that aims to sensitize tumor cells with low NO rates, potentializing the chemotherapy treatment. Thus, this project consists in the development of nanoparticles carrying chemotherapeutic agents functionalized with modified chitosan molecules, allowing the release of nitric oxide (NO), an endogenous signaling molecule, capable of sensitizing the tumor cells by several routes and, therefore, enabling a more effective treatment. Hybrid nanoparticles will be synthesized, functionalized and characterized by several techniques. In vitro antitumoral experiments will be carried out in order to investigate the potential and the different death pathways involved in the treatment employing the synthesized nanoparticles. Therefore, this project allows advances in the area of Cancer NanoMedicine combined with NO, generating scientific and technological contributions in the area of nanomaterials, NO, Biology and Medicine. (AU)

Scientific publications

(24)

(The scientific publications listed on this page originate from the Web of Science or SciELO databases. Their authors have cited FAPESP grant or fellowship project numbers awarded to Principal Investigators or Fellowship Recipients, whether or not they are among the authors. This information is collected automatically and retrieved directly from those bibliometric databases.)

PIERETTI, JOANA CLAUDIO; ARMENTANO, GIOVANA MARCHINI; CARNEIRO-RAMOS, MARCELA SORELLI; SEABRA, AMEDEA BAROZZI. Nitric oxide tuning enhances cytotoxicity and reduces inflammation in prostate cancer nanotherapy. NITRIC OXIDE-BIOLOGY AND CHEMISTRY, v. 158, p. 8-pg., 2025-10-01. (22/14645-2, 20/03646-2, 22/01124-4, 24/12112-2)

GOMES, DIEGO G.; SANADA, KARINA; PIERETTI, JOANA C.; SHIGUEOKA, LUCIANA H.; SERA, GUSTAVO H.; SEABRA, AMEDEA B.; OLIVEIRA, HALLEY C.. Nanoencapsulation Boosts the Copper-Induced Defense Responses of a Susceptible Coffea arabica Cultivar against Hemileia vastatrix. ANTIBIOTICS-BASEL, v. 12, n. 2, p. 22-pg., 2023-02-01. (22/00321-0, 20/03646-2)

NERES-SANTOS, RAQUEL SILVA; JUNHO, CAROLINA VICTORIA CRUZ; PANICO, KARINE; CAIO-SILVA, WELLINGTON; PIERETTI, JOANA CLAUDIO; TAMASHIRO, JULIANA ALMEIDA; SEABRA, AMEDEA BAROZZI; RIBEIRO, CESAR AUGUSTO JOAO; CARNEIRO-RAMOS, MARCELA SORELLI. Mitochondrial Dysfunction in Cardiorenal Syndrome 3: Renocardiac Effect of Vitamin C. CELLS, v. 10, n. 11, NOV 2021. (15/25541-0, 18/08194-2, 19/11077-0, 20/03646-2, 15/19107-5)

TORTELLA, GONZALO; RUBILAR, OLGA; PIERETTI, JOANA C.; FINCHEIRA, PAOLA; DE MELO SANTANA, BIANCA; FERNANDEZ-BALDO, MARTIN A.; BENAVIDES-MENDOZA, ADALBERTO; SEABRA, AMEDEA B.. Nanoparticles as a Promising Strategy to Mitigate Biotic Stress in Agriculture. ANTIBIOTICS-BASEL, v. 12, n. 2, p. 20-pg., 2023-02-01. (22/00321-0, 20/08566-7, 20/03646-2)

SANTANA, BIANCA DE MELO; PIERETTI, JOANA CLAUDIO; GOMES, RAFAEL NUNES; CERCHIARO, GISELLE; SEABRA, AMEDEA BAROZZI. Cytotoxicity towards Breast Cancer Cells of Pluronic F-127/Hyaluronic Acid Hydrogel Containing Nitric Oxide Donor and Silica Nanoparticles Loaded with Cisplatin. PHARMACEUTICS, v. 14, n. 12, p. 16-pg., 2022-12-01. (20/03646-2, 20/08566-7, 22/00321-0)

PELEGRINO, MILENA T.; PIERETTI, JOANA C.; LANGE, CAMILA NEVES; KOHATSU, MARCIO YUKIHIRO; FREIRE, BRUNA MOREIRA; BATISTA, BRUNO LEMOS; FINCHEIRA, PAOLA; TORTELLA, GONZALO R.; RUBILAR, OLGA; SEABRA, AMEDEA B.. Foliar spray application of CuO nanoparticles (NPs) and S-nitrosoglutathione enhances productivity, physiological and biochemical parameters of lettuce plants. JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY, v. 96, n. 8, p. 2185-2196, AUG 2021. (18/08194-2, 20/03646-2)

NUNES, RENAN S.; MARIANO, KELLI C. FREITAS; PIERETTI, JOANA C.; DOS REIS, ROBERTA A.; SEABRA, AMEDEA B.. Innovative nitric oxide-releasing nanomaterials: Current progress, trends, challenges, and perspectives in cardiovascular therapies. NITRIC OXIDE-BIOLOGY AND CHEMISTRY, v. 156, p. 15-pg., 2025-06-01. (24/12112-2, 22/14645-2, 23/16363-7, 24/04079-5, 20/03646-2)

NUNES, RENAN S.; CINEL, VICTOR D. P.; PIERETTI, JOANA C.; MARIANO, KELLI C. F.; DOS REIS, ROBERTA A.; HALFELD, MORGANA; SEABRA, AMEDEA B.. Multivariate chemometric design of nitric oxide-releasing chitosan nanoparticles for skin-related biomedical applications. NANOSCALE, v. 17, n. 21, p. 17-pg., 2025-05-08. (22/14645-2, 24/04079-5, 24/20778-0, 20/03646-2, 23/16363-7, 24/12112-2)

DA VEIGA, JULIA C.; SILVEIRA, NEIDIQUELE M.; SEABRA, AMEDEA B.; PIERETTI, JOANA C.; BOZA, YOLANDA; JACOMINO, ANGELO P.; CESAR FILHO, JULIO Z.; CAMPAGNOLI, VINICIUS P.; CIA, PATRICIA; BRON, ILANA U.. Spraying with encapsulated nitric oxide donor reduces weight loss and oxidative damage in papaya fruit. NITRIC OXIDE-BIOLOGY AND CHEMISTRY, v. 150, p. 10-pg., 2024-07-30. (23/13662-3, 20/03646-2, 22/00321-0)

DOS REIS, ROBERTA ALBINO; BOUDIER, ARIANE; PIQUARD, FLAVIAN; PIERETI, JOANA C.; SEABRA, AMEDEA B.; CLAROT, IGOR. Nitric oxide detection by electrochemistry selective probe: calibration in the study environment is mandatory. NITRIC OXIDE-BIOLOGY AND CHEMISTRY, v. 157, p. 9-pg., 2025-04-25. (22/14645-2, 24/12112-2, 23/16363-7, 20/03646-2)

DO CARMO, GIOVANNA CAMARGO; DE MELLO, JOSE VICTOR SOTO; PREISLER, ANA CRISTINA; DE LIMA, JOHN DAVID OLIVEIRA; PEREIRA, RONEY HENRIQUE; PIERETTI, JOANA CLAUDIO; STOLF-MOREIRA, RENATA; PIMENTA, JOSE ANTONIO; SEABRA, AMEDEA BAROZZI; OLIVEIRA, HALLEY CAIXETA. Effects of nanoencapsulated nitric oxide donor on Cecropia pachystachya Trécul and Cariniana estrellensis (Raddi) Kuntze seedlings subjected to short and long-term water deficit. TREES-STRUCTURE AND FUNCTION, v. 39, n. 4, p. 14-pg., 2025-07-22. (22/14645-2, 24/12112-2, 20/03646-2)

FREIRE, BRUNA MOREIRA; LANGE, CAMILA NEVES; CAVALCANTI, YASMIN TAVARES; MONTEIRO, LUCILENA REBELO; PIERETTI, JOANA CLAUDIO; SEABRA, AMEDEA BAROZZI; BATISTA, BRUNO LEMOS. The dual effect of Selenium nanoparticles in rice seedlings: From increasing antioxidant activity to inducing oxidative stress. PLANT STRESS, v. 11, p. 8-pg., 2024-01-30. (14/05151-0, 22/00321-0, 16/10060-9, 20/00284-2, 22/00208-0, 20/03646-2, 22/04254-6)

PIERETTI, JOANA CLAUDIO; PELEGRINO, MILENA TREVISAN; BOUDIER, ARIANE; SEABRA, AMEDEA BAROZZI. Recent progress in the toxicity of nitric oxide-releasing nanomaterials. MATERIALS ADVANCES, v. 2, n. 23, OCT 2021. (19/07766-5, 18/08194-2, 20/03646-2)

SILVA, ALINE CASTRO; DOS SANTOS, ALISSON GLEYSSON RODRIGUES; PIERETTI, JOANA CLAUDIO; ROLIM, WALLACE ROSADO; SEABRA, AMEDEA BAROZZI; AVILA, DAIANA SILVA. Iron oxide/silver hybrid nanoparticles impair the cholinergic system and cause reprotoxicity in Caenorhabditis elegans. Food and Chemical Toxicology, v. 179, p. 14-pg., 2023-09-01. (22/00321-0, 20/03646-2)

SEABRA, AMEDEA B.; PIERETTI, JOANA C.; SANTANA, BIANCA DE MELO; HORUE, MANUEL; TORTELLA, GONZALO R.; CASTRO, GUILLERMO R.. Pharmacological applications of nitric oxide-releasing biomaterials in human skin. International Journal of Pharmaceutics, v. 630, p. 14-pg., 2023-01-05. (22/00321-0, 20/03646-2)

PIERETTI, JOANA CLAUDIO; FREIRE, BRUNA MOREIRA; ARMENTANO, GIOVANA MARCHINI; SANTANA, BIANCA DE MELO; BATISTA, BRUNO LEMOS; CARNEIRO-RAMOS, MARCELA SORELLI; SEABRA, AMEDEA BAROZZI. Chronic exposure to nitric oxide sensitizes prostate cancer cells and improved ZnO/CisPt NPs cytotoxicity and selectivity. International Journal of Pharmaceutics, v. 640, p. 8-pg., 2023-05-10. (22/00321-0, 20/03646-2, 20/08566-7, 22/00153-0)

SEABRA, AMEDEA B.; SILVEIRA, NEIDIQUELE M.; RIBEIRO, RAFAEL, V; PIERETTI, JOANA C.; BARROSO, JUAN B.; CORPAS, FRANCISCO J.; PALMA, JOSE M.; HANCOCK, JOHN T.; PETRIVALSKY, MAREK; GUPTA, KAPUGANTI J.; et al. Nitric oxide-releasing nanomaterials: from basic research to potential biotechnological applications in agriculture. NEW PHYTOLOGIST, v. 234, n. 4, p. 7-pg., 2022-03-29. (20/03646-2, 12/19167-0, 17/11279-7, 18/08194-2, 19/15095-3, 15/21546-7)

GOMES, DIEGO G. G.; DEBIASI, TATIANE V. V.; PELEGRINO, MILENA T. T.; PEREIRA, RODRIGO M. M.; ONDRASEK, GABRIJEL; BATISTA, BRUNO L. L.; SEABRA, AMEDEA B. B.; OLIVEIRA, HALLEY C. C.. Soil Treatment with Nitric Oxide-Releasing Chitosan Nanoparticles Protects the Root System and Promotes the Growth of Soybean Plants under Copper Stress. PLANTS-BASEL, v. 11, n. 23, p. 24-pg., 2022-12-01. (18/08194-2, 20/03646-2, 22/00321-0)

PELA, VINICIUS TAIOQUI; BRITO, LEONARDO; TAIRA, EVEN AKEMI; HENRIQUE-SILVA, FLAVIO; PIERETTI, JOANA CLAUDIO; SEABRA, AMEDEA BAROZZI; BALDINI CARDOSO, CRISTIANE DE ALMEIDA; DE SOUZA, EDUARDO PEREIRA; GROISMAN, SONIA; RODRIGUES, MARCELA CHARANTOLA; et al. Preventive effect of chitosan gel containing CaneCPI-5 against enamel erosive wear in situ. CLINICAL ORAL INVESTIGATIONS, v. 26, n. 11, p. 9-pg., 2022-07-13. (20/03646-2, 18/08194-2, 17/04857-4, 18/12041-7, 21/02366-9)

DOS REIS, ROBERTA A.; DA SILVA, LEONARDO L.; PIERETTI, JOANA C.; CREUSOT, BENJAMIN; LAHOUARI, SEPHORA; FRANCIUS, GREGORY; DA SILVA, RICARDO A. G.; CLAROT, IGOR; BOUDIER, ARIANE; SEABRA, AMEDEA B.. Eco-friendly synthesis and biomedical potential of zinc oxide nanoparticles using Mentha piperita aqueous extract: comparative analysis with chemically synthesized and commercial nanoparticles. Bioprocess and Biosystems Engineering, v. 48, n. 8, p. 16-pg., 2025-05-24. (22/13444-3, 24/12112-2, 23/16363-7, 22/14645-2, 20/03646-2)

ARMENTANO, GIOVANA MARCHINI; PIERETTI, JOANA CLAUDIO; FALCONI, CARLOS ALEXANDRE; SEABRA, AMEDEA BAROZZI; CARNEIRO-RAMOS, MARCELA SORELLI. Nitric Oxide Plays a Dual Role in Cardiorenal Syndrome in Vitro Model. CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, v. 58, n. 1, p. 16-pg., 2024-01-01. (22/01124-4, 22/00153-0, 19/11077-0, 20/03646-2)

PREISLER, ANA CRISTINA; DO CARMO, GIOVANNA CAMARGO; DA SILVA, RAFAEL CAETANO; SIMOES, ANA LUISA DE OLIVEIRA; IZIDORO, JULIANA DE CARVALHO; PIERETTI, JOANA CLAUDIO; DOS REIS, ROBERTA ALBINO; JACOB, ANDRE LUIZ FLORIANO; SEABRA, AMEDEA BAROZZI; OLIVEIRA, HALLEY CAIXETA. Improving Soybean Germination and Nodule Development with Nitric Oxide-Releasing Polymeric Nanoparticles. PLANTS-BASEL, v. 14, n. 1, p. 19-pg., 2025-01-01. (24/12112-2, 20/03646-2, 23/16363-7, 22/03914-2)

PIERETTI, JOANA C.; HORNE, THAISSA L.; GARCIA-VILLASANTE, NATALIA; SEABRA, AMEDEA B.; MUNTANE, JORDI. Zinc-Based Nanoparticles, but Not Silicon-Based Nanoparticles, Accumulate in Mitochondria and Promote Cell Death in Liver Cancer Cells. INTERNATIONAL JOURNAL OF NANOMEDICINE, v. 19, p. 12-pg., 2024-01-01. (21/12705-5, 20/03646-2, 22/14645-2)

PIERETTI, JOANA C.; PELEGRINO, MILENA T.; SILVEIRA, NEIDIQUELE M.; RODRIGUES, MAIARA G.; SEABRA, AMEDEA B.. State-of-the-Art and Perspectives for Nanomaterials Combined with Nitric Oxide Donors: From Biomedical to Agricultural Applications. ACS APPLIED NANO MATERIALS, v. 7, n. 16, p. 20-pg., 2023-10-20. (20/03646-2, 22/00321-0)