Combinatorial therapy using polymersomes decorated with transferrin and incorporated into chitosan hydrogels as smart drug delivery systems for melanoma tumor cells

• Grant number: 17/10789-1
• Support Opportunities: Research Grants - Young Investigators Grants
• Duration: June 01, 2018 - June 30, 2023
• Field of knowledge: Engineering - Biomedical Engineering - Bioengineering
• Principal Investigator: André Moreni Lopes
• Grantee: André Moreni Lopes
• Host Institution: Escola de Engenharia de Lorena (EEL). Universidade de São Paulo (USP). Lorena , SP, Brazil
• Associated researchers: Carlota de Oliveira Rangel Yagui ; Leandro Ramos Souza Barbosa ; Luciana Biagini Lopes ; Priscila Gava Mazzola
• Associated scholarship(s): 20/03727-2 - Polymersomes development aiming at the co-encapsulation of drugs for application in cancer therapy, BP.MS; 19/08549-8 - Polymersomes decorated with transferrin and evaluation of their stability and drug release behavior, BP.IC; 18/10799-0 - Combinatorial therapy using polymersomes decorated with transferrin and incorporated into chitosan hydrogels as smart drug delivery systems for melanoma tumor cells, BP.JP

Abstract

In this research project, we propose to investigate a novel co-therapy approach using smart drug delivery systems in melanoma therapy. This approach will employ multi-drug delivery from nanostructures of polymer vesicle-type, otherwise known as polymersomes (Ps), which represents an innovative alternative for the treatment of cancer. Specifically, vemurafenib, a specific inhibitor of mutated B-Raf protein at the V600E site, and doxorubicin, a broad spectrum drug, that can act on wild B-Raf proteins (non-mutated), correspond in two important drugs for melanoma cancer therapy. Co-encapsulation of these drugs in Ps can favor not only the stability of the molecules, but also increase the half-life of these molecules in the bloodstream and also possible synergistic effect for tumor cells. In addition to this approach, we propose the use of three-dimensional (3-D) structures of chitosan hydrogels as platforms of Ps. We expect this platform to have advantages such as mucoadhesiveness, biocompatibility and controlled and sustained release, which makes it potentially interesting for application in transdermal route for drug delivery. Moreover, by decorating the surface of these nanostructures with affinity ligand such as transferrin (Tf), we can increase the specificity of Ps toward tumor cells and achieve a greater therapeutic efficacy and decrease of toxicity. In this work, it will be investigated: (i) development of Ps in different conditions, (ii) drug encapsulation (individual and simultaneous), (iii) decoration of Ps with Tf, (iv) characterization of Ps formulations, (v) stability and incorporation of Ps in the chitosan hydrogels under different conditions, (vi) stability of the hydrogel with and without Ps, (vii) Ps release incorporated into the hydrogel in conditions simulating the transdermal route, and (viii) comparison of cytotoxic effect in tumor cells (either BRAF mutated or not) versus normal cells. (AU)

Scientific publications

(13)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE OLIVEIRA, FERNANDA; LIMA, CAIO DE AZEVEDO; LOPES, ANDRE MORENI; VIANA MARQUES, DANIELA DE ARAUJO; DRUZIAN, JANICE IZABEL; PESSOA JUNIOR, ADALBERTO; SANTOS-EBINUMA, VALERIA CARVALHO. Microbial Colorants Production in Stirred-Tank Bioreactor and Their Incorporation in an Alternative Food Packaging Biomaterial. JOURNAL OF FUNGI, v. 6, n. 4, DEC 2020. (18/06908-8, 18/10799-0, 17/10789-1, 14/01580-3, 13/05039-2)

D'ANGELO, NATALIA A.; NORONHA, MARIANA A.; KURNIK, ISABELLE S.; CAMARA, MAYRA C. C.; VIEIRA, JORGE M.; ABRUNHOSA, LUIS; MARTINS, JOANA T.; ALVES, THAIS F. R.; TUNDISI, LOUISE L.; ATAIDE, JANAINA A.; et al. Curcumin encapsulation in nanostructures for cancer therapy: A 10-year overview. International Journal of Pharmaceutics, v. 604, JUL 15 2021. (18/10799-0, 18/07707-6, 18/06475-4, 17/10789-1, 19/08549-8, 20/03727-2)

D'ANGELO, NATALIA A.; CAMARA, MAYRA C. C.; NORONHA, MARIANA A.; GROTTO, DENISE; CHORILLI, MARLUS; LOURENCO, FELIPE R.; RANGEL-YAGUI, CARLOTA DE O.; LOPES, ANDRE M.. evelopment of PEG-PCL-based polymersomes through design of experiments for co-encapsulation of vemurafenib and doxorubicin as chemotherapeutic drug. JOURNAL OF MOLECULAR LIQUIDS, v. 349, MAR 1 2022. (17/10789-1, 18/10799-0, 20/03727-2, 19/08549-8)

DE BARROS, CECILIA; ARANHA, NORBERTO; SEVERINO, PATRICIA; SOUTO, ELIANA B.; ZIELINSKA, ALEKSANDRA; LOPES, ANDRE; RIOS, ALESSANDRA; BATAIN, FERNANDO; CRESCENCIO, KESSI; CHAUD, MARCO; et al. Quality by Design Approach for the Development of Liposome Carrying Ghrelin for Intranasal Administration. PHARMACEUTICS, v. 13, n. 5, MAY 2021. (18/10799-0, 17/10789-1)

RODRIGUES, DAVID; PILLACA-PULLO, OMAR; TORRES-OBREQUE, KARIN; FLORES-SANTOS, JUAN; SANCHEZ-MOGUEL, IGNACIO; PIMENTA, V, MARCELA; BASI, TAJINDAR; CONVERTI, ATTILIO; LOPES, ANDRE M.; MONTEIRO, GISELE; et al. Fed-Batch Production of Saccharomyces cerevisiae L-Asparaginase II by Recombinant Pichia pastoris MUTs Strain. FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY, v. 7, FEB 8 2019. (13/08617-7, 17/10789-1)

PACHIONI-VASCONCELOS, JULIANA DE ALMEIDA; APOLINARIO, ALEXSANDRA CONCEICAO; LOPES, ANDRE MORENI; PESSOA, JR., ADALBERTO; BARBOSA, LEANDRO RAMOS SOUZA; RANGEL-YAGUI, CARLOTA DE OLIVEIRA. Compartmentalization of therapeutic proteins into semi-crystalline PEG-PCL polymersomes. SOFT MATERIALS, v. 19, n. 2, p. 222-230, APR 3 2021. (13/08617-7, 14/10456-4, 17/10789-1)

PILLACA-PULLO, OMAR; RODRIGUES, DAVID; SANCHEZ-MOGUEL, IGNACIO; LOPES, ANDRE; PIMENTA, MARCELA; BASI, TAJINDAR; FEITOSA, VALKER; IRIS ZAVALETA, AMPARO; MONTEIRO, GISELE; PESSOA JR, ADALBERTO; et al. Recombinantl-asparaginase production usingPichia pastoris(MUT(s)strain): establishment of conditions for growth and induction phases. JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY, v. 96, n. 1, AUG 2020. (13/08617-7, 17/10789-1)

KURNIK, ISABELLE S.; D'ANGELO, NATALIA A.; MAZZOLA, PRISCILA G.; CHORILLI, MARLUS; KAMEI, DANIEL T.; PEREIRA, JORGE F. B.; VICENTE, ANTONIO A.; LOPES, ANDRE M.. Polymeric micelles using cholinium-based ionic liquids for the encapsulation and release of hydrophobic drug molecules. BIOMATERIALS SCIENCE, v. 9, n. 6, p. 2183-2196, MAR 21 2021. (18/10799-0, 20/03727-2, 14/16424-7, 18/05111-9, 19/05624-9, 17/10789-1, 19/08549-8)

PEREZ-SANCHEZ, GERMAN; SCHAEFFER, NICOLAS; LOPES, ANDRE M.; PEREIRA, JORGE F. B.; COUTINHO, JOAO A. P.. Using coarse-grained molecular dynamics to understand the effect of ionic liquids on the aggregation of Pluronic copolymer solutions. Physical Chemistry Chemical Physics, v. 23, n. 10, p. 5824-5833, MAR 14 2021. (18/10799-0, 14/16424-7, 17/10789-1)

KURNIK, ISABELLE S.; MUSSAGY, CASSAMO U.; PEREIRA, JORGE F. B.; LOPES, ANDRE M.. Amphiphilic copolymer aqueous solutions with cholinium ionic liquids as adjuvants: New insights into determination of binodal curves and phase-separation mechanisms. JOURNAL OF MOLECULAR LIQUIDS, v. 318, NOV 15 2020. (14/16424-7, 18/05111-9, 19/05624-9, 17/10789-1, 18/10799-0, 19/08549-8)

LOPES, ANDRE MORENI; DAHMS, HANS-UWE; CONVERTI, ATTILIO; MARIOTTINI, GIAN LUIGI. Role of model organisms and nanocompounds in human health risk assessment. ENVIRONMENTAL MONITORING AND ASSESSMENT, v. 193, n. 5, MAY 2021. (18/10799-0, 17/10789-1)

CASTANHO, NATHALIA R. C. M.; DE OLIVEIRA, RENAN A.; BATISTA, BRUNO L.; FREIRE, BRUNA M.; LANGE, CAMILA; LOPES, ANDRE M.; JOZALA, ANGELA F.; GROTTO, DENISE. Comparative Study on Lead and Copper Biosorption Using Three Bioproducts from Edible Mushrooms Residues. JOURNAL OF FUNGI, v. 7, n. 6, JUN 2021. (18/10799-0, 17/10789-1, 16/22873-4)

KURNIK, ISABELLE S.; NORONHA, MARIANA A.; CAMARA, MAYRA C. C.; MAZZOLA, PRISCILA G.; VICENTE, ANTONIO A.; PEREIRA, JORGE F. B.; LOPES, ANDRE M.. Separation and purification of curcumin using novel aqueous two-phase micellar systems composed of amphiphilic copolymer and cholinium ionic liquids. Separation and Purification Technology, v. 250, NOV 1 2020. (14/16424-7, 17/10789-1, 19/05624-9, 18/05111-9, 19/08549-8, 18/10799-0)