Development of nanocarriers based on dendrimers and polymer nanoparticles for selective delivery of goniothalamin, piplartine and Monastrol

• Grant number: 17/06146-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2017
• End date: August 31, 2022
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Ronaldo Aloise Pilli
• Grantee: Carolyne Brustolin Braga
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID
• Associated scholarship(s): 18/24020-4 - Polynorbornene-goniothalamin and polynorbornene-piplartine conjugates for cancer therapy, BE.EP.PD

Abstract

Biodegradable and biocompatible dendrimers and acetalated dextran (Ac-DEX) polymeric nanoparticles hold great promise as nanocarriers for the delivery of bioactivecompounds for anticancer therapy. The advantages of using these nanomaterials as drug delivery systems include enhanced water solubility, tumor-specific accumulation and improved antitumor efficacy, while reducing nonspecific toxicity, compared to the conventional small-molecule anticancer agents. Taking these aspects into account, together with the potent antitumor activity presented by goniothalamin (GTN), piplartine (PPT) and monastrol (MNT) against several tumorcell lines, the main goal of the current project is the development of new nanosystems for the selective delivery of each of these small molecules to diseased tissues. Specifically, this project aims to conjugate GTN, PPT and MNT via Click Chemistry to well-defined dendrimers, as well as to encapsulate these three bioactive compounds in Ac-DEX nanoparticles. Our strategy includes the synthesis of GTN, PPT and MNT analogues for conjugation to dendrimers in order to produce an efficient system for delivering of the corresponding active molecule to the tumor region. Also, the project will focus on obtaining enhanced formulations, through optimization, for example, of the loading and release properties of the delivery systems. The cytotoxicity of the new nanomaterials will be tested against several cell lines (tumor and healthy cells), and compared with the corresponding ones for the free drugs and empty nanocarriers, in order to define if these materials are valid candidates for the treatment of cancer. (AU)

Scientific publications

(19)

(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.)

DE SERRES-BERARD, THIERY; BECHER, TIAGO B.; BRAGA, CAROLYNE B.; ORNELAS, CATIA; BERTHOD, FRANCOIS. Neuropeptide Substance P Released from a Nonswellable Laponite-Based Hydrogel Enhances Wound Healing in a Tissue-Engineered Skin In Vitro. ACS APPLIED POLYMER MATERIALS, v. 2, n. 12, p. 5790-5797, DEC 11 2020. (18/02093-0, 17/06146-8, 13/11519-7)

MEIRELLES, MATHEUS A.; BRAGA, CAROLYNE B.; ORNELAS, CATIA; PILLI, RONALDO A.. Synthesis of Nitrogen-Containing Goniothalamin Analogues with Higher Cytotoxic Activity and Selectivity against Cancer Cells. CHEMMEDCHEM, v. 14, n. 15, JULY 2019. (13/07607-8, 18/02093-0, 17/06146-8)

PERLI, GABRIEL; WANG, QI; BRAGA, CAROLYNE B.; BERTUZZI, DIEGO L.; FONTANA, LINIQUER A.; SOARES, MARCO C. P.; RUIZ, JAIME; MEGIATTO, JR., JACKSON D.; ASTRUC, DIDIER; ORNELAS, CATIA. Self-Assembly of a Triazolylferrocenyl Dendrimer in Water Yields Nontraditional Intrinsic Green Fluorescent Vesosomes for Nanotheranostic Applications. Journal of the American Chemical Society, v. 143, n. 33, p. 12948-12954, AUG 25 2021. (18/02093-0, 13/22160-0, 21/00555-9, 17/06146-8)

GRIGOLO, THIAGO A.; BRAGA, CAROLYNE B.; ORNELAS, CATIA; RUSSOWSKY, DENNIS; FERREIRA-SILVA, GUILHERME A.; IONTA, MARISA; PILLI, RONALDO A.. Hybrids of 4-hydroxy derivatives of goniothalamin and piplartine bearing a diester or a 1,2,3-triazole linker as antiproliferative agents. BIOORGANIC CHEMISTRY, v. 116, NOV 2021. (17/06146-8, 18/02093-0, 13/07607-8, 19/13104-5)

PERLI, GABRIEL; BERTUZZI, DIEGO L.; SOUTO, DENIO E. P.; RAMOS, MIGUEL D.; BRAGA, CAROLYNE B.; AGUIAR, SAMILE B.; ORNELAS, CATIA. Synthesis and Characterization of Dendronized Gold Nanoparticles Bearing Charged Peripheral Groups with Antimicrobial Potential. NANOMATERIALS, v. 12, n. 15, p. 15-pg., 2022-08-01. (18/02093-0, 17/06146-8, 15/04929-0, 21/00555-9)

DE SERRES-BERARD, THIERY; BECHER, TIAGO B.; BRAGA, CAROLYNE B.; ORNELAS, CATIA; BERTHOD, FRANCOIS. Neuropeptide Substance P Released from a Nonswellable Laponite-Based Hydrogel Enhances Wound Healing in a Tissue-Engineered Skin In Vitro. ACS APPLIED POLYMER MATERIALS, v. 2, n. 12, p. 8-pg., 2020-12-11. (13/11519-7, 18/02093-0, 17/06146-8)

DE SOUZA, VANESSA P.; SANTOS, FABIANO S.; RODEMBUSCH, FABIANO S.; BRAGA, CAROLYNE B.; ORNELAS, CATIA; PILLI, RONALDO A.; RUSSOWSKY, DENNIS. Hybrid 3,4-dihydropyrimidin-2-(thi)ones as dual-functional bioactive molecules: fluorescent probes and cytotoxic agents to cancer cells. NEW JOURNAL OF CHEMISTRY, v. 44, n. 29, p. 12440-12451, AUG 7 2020. (17/06146-8, 19/13104-5, 18/02093-0)

DE SOUZA, VANESSA P.; GOMES, IZABELA N. F.; SANTOS, SAMUEL J.; BRAGA, CAROLYNE B.; BEZERRA, ARYEL J. A.; PHILOT, ERIC A.; RAMOS, CINTIA R. N.; PANTALEAO, SIMONE Q.; DA SILVA, LUCIANE S.; PILLI, RONALDO A.; et al. Design, synthesis and evaluation of fluorescent dihydropyridine-dihydropyrimidinone hybrids as inducers of cell-cycle arrest in a prostate cancer cell line via Aurora kinase interactions. RSC MEDICINAL CHEMISTRY, v. N/A, p. 21-pg., 2025-09-16. (19/13104-5, 23/02032-9, 13/07607-8, 17/06146-8)

PERLI, GABRIEL; BRAGA, CAROLYNE B.; BERTUZZI, DIEGO L.; SOARES, MARCO C. P.; RAMOS, MIGUEL; ES, ISMAIL; ORNELAS, CATIA. Unlocking the synthesis of ultra-small silver nanoparticles via a reactive formamide-driven nanoemulsion within Ac-Dex nanoparticles. MATERIALS TODAY CHEMISTRY, v. 47, p. 10-pg., 2025-07-07. (17/06146-8, 17/24488-3)

BRAGA, CAROLYNE B.; KIDO, LARISSA A.; LIMA, ELLEN N.; LAMAS, CELINA A.; CAGNON, VALERIA H. A.; ORNELAS, CATIA; PILLI, RONALDO A.. Enhancing the Anticancer Activity and Selectivity of Goniothalamin Using pH-Sensitive Acetalated Dextran (Ac-Dex) Nanoparticles: A Promising Platform for Delivery of Natural Compounds. ACS BIOMATERIALS SCIENCE & ENGINEERING, v. 6, n. 5, SI, p. 2929-2942, MAY 2020. (18/02093-0, 17/06146-8, 19/13104-5, 13/07607-8)

BERTUZZI, DIEGO L.; PERLI, GABRIEL; BRAGA, CAROLYNE B.; ORNELAS, CATIA. Synthesis, characterization, and anticancer activity of folate gamma-ferrocenyl conjugatest. NEW JOURNAL OF CHEMISTRY, v. 44, n. 12, p. 4694-4703, MAR 28 2020. (18/02093-0, 15/04929-0, 17/06146-8)

BRAGA, CAROLYNE B.; PILLI, RONALDO A.; ORNELAS, CATIA; WECK, MARCUS. ear-Infrared Fluorescent Micelles from Poly(norbornene) Brush Triblock Copolymers for Nanotheranostic. Biomacromolecules, v. 22, n. 12, p. 5290-5306, DEC 13 2021. (13/07607-8, 19/13104-5, 14/50906-9, 18/24020-4, 17/06146-8)

LIMA, MARIA L. S. O.; BRAGA, CAROLYNE B.; BECHER, TIAGO B.; ODRIOZOLA-GIMENO, MIKEL; TORRENT-SUCARRAT, MIQUEL; RIVILLA, IVAN; COSSIO, FERNANDO P.; MARSAIOLI, ANITA J.; ORNELAS, CATIA. Fluorescent Imidazo[1,2-a]pyrimidine Compounds as Biocompatible Organic Photosensitizers that Generate Singlet Oxygen: A Potential Tool for Phototheranostics. CHEMISTRY-A EUROPEAN JOURNAL, v. 27, n. 20, JAN 2021. (17/06146-8, 18/02093-0)

BRAGA, CAROLYNE B.; PERLI, GABRIEL; BECHER, TIAGO B.; OMELAS, CATIA. Biodegradable and pH-Responsive Acetalated Dextran (Ac-Dex) Nanoparticles for NIR Imaging and Controlled Delivery of a Platinum-Based Prodrug into Cancer Cells. MOLECULAR PHARMACEUTICS, v. 16, n. 5, p. 2083-2094, MAY 2019. (18/02093-0, 17/24488-3, 17/06146-8)

BERTUZZI, DIEGO L.; BRAGA, CAROLYNE B.; PERLI, GABRIEL; ORNELAS, CATIA. Water-Soluble Well-Defined Bifunctional Ferrocenyl Dendrimer with Anti-Cancer Activity. European Journal of Inorganic Chemistry, v. 2022, n. 9, p. 6-pg., 2022-02-01. (17/06146-8, 15/04929-0, 21/00555-9)

BRAGA, CAROLYNE B.; PERLI, GABRIEL; WANG, QI; WYLIE, LUKE; BERTUZZI, DIEGO L.; SOARES, MARCO C. P.; RAMOS, MIGUEL D.; RUIZ, JAIME; PADUA, AGILIO; ASTRUC, DIDIER; et al. Unveiling Hierarchical Self-Assembly of Triazolylferrocenyl Dendrimers: Producing Non-Traditional Intrinsically Green Fluorescent Vesosomes for Nanotheranostics. ADVANCED HEALTHCARE MATERIALS, v. N/A, p. 17-pg., 2024-09-15. (17/24488-3, 17/06146-8, 18/02093-0, 21/00555-9)

BRAGA, CAROLYNE BRUSTOLIN; MILAN, JULIO CESAR; MEIRELLES, MATHEUS ANDRADE; ZAVAN, BRUNO; FERREIRA-SILVA, GUILHERME ALVARO; CAIXETA, ESTER SIQUEIRA; IONTA, MARISA; PILLI, RONALDO A.. Furoxan-piplartine hybrids as effective NO donors and ROS inducers in PC3 cancer cells: design, synthesis, and biological evaluation. RSC MEDICINAL CHEMISTRY, v. 15, n. 11, p. 17-pg., 2024-08-23. (19/20735-1, 13/07607-8, 17/06146-8, 19/13104-5)

BRAGA, CAROLYNE BRUSTOLIN; PERLI, GABRIEL; FONSECA, RAFAEL; GRIGOLO, THIAGO AUGUSTO; IONTA, MARISA; ORNELAS, CATIA; PILLI, RONALDO A.. Enhanced Synergistic Efficacy Against Breast Cancer Cells Promoted by Co-Encapsulation of Piplartine and Paclitaxel in Acetalated Dextran Nanoparticles. MOLECULAR PHARMACEUTICS, v. 21, n. 11, p. 21-pg., 2024-10-04. (19/13104-5, 13/07607-8, 17/06146-8, 18/02093-0, 14/50938-8)

BRAGA, CAROLYNE B.; KIDO, LARISSA A.; LIMA, ELLEN N.; LAMAS, CELINA A.; CAGNON, VALERIA H. A.; ORNELAS, CATIA; PILLI, RONALDO A.. Enhancing the Anticancer Activity and Selectivity of Goniothalamin Using pH-Sensitive Acetalated Dextran (Ac-Dex) Nanoparticles: A Promising Platform for Delivery of Natural Compounds. ACS BIOMATERIALS SCIENCE & ENGINEERING, v. 6, n. 5, p. 14-pg., 2020-05-01. (18/02093-0, 17/06146-8, 13/07607-8, 19/13104-5)