Manufacturing and biological evaluations of stimuli-responsive polymersomes towards enhanced efficacy of cancer therapies

• Grant number: 19/06634-8
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2020
• End date: June 30, 2023
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Physical-Chemistry
• Agreement: Czech Science Foundation (GACR)
• Principal Investigator: Fernando Carlos Giacomelli
• Grantee: Fernando Carlos Giacomelli
• Principal researcher abroad: Peter Cernoch
• Institution abroad: Czech Academy of Sciences (CAS), Czech Republic
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

The most recent survey by the International Agency for Research on Cancer reported that the global death related to the malignancy was about 9.6 million in 2018 (21% higher than that in 2008). This number is predicted to be as high as 19.3 million by 2025 calling for improvements in cancer treatments. In the last decades, cancer therapy has also been tackled to design carriers that can navigate the body and deliver their cargos in desired site. The most successful up-to-date carrier is the pegylated liposomal formulation of doxorubicin (DOX) Doxil/Caelyx which is 100nm-sized vesicles encapsulating 10,000-15,000 DOX molecules. Doxil/Caelyx becomes one of the most sale nanotechnologies in the history of the chemotherapy which expected to generate revenue of 1.39 billion USD for 2025.Despite a 60-fold increase in the fraction of recovered dose in blood, a 4-fold increase of the recovered dose in liver and spleen and a 25-fold increase of the concentration of the liposomal formulation in tumor, the Doxil/Caelyx formulation still compromise the effectivity of the treatment due to lack of specificity and DOX leakage during blood circulation resulting in several side-effects including hand-foot syndrome, mouth pain (stomatitis), low white blood cell counts, low platelet counts, anemia, nausea and vomiting. We wish to fundamentally contribute to circumvent such drawback by designing stimuli-responsive vesicles able to controlled release the drug only under response to the inherent characteristics of the tumor microenvironment. Such features may enhance the therapeutic outcomes in comparison to the conventional cancer therapies. (AU)

Scientific publications

(8)

(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, FERNANDO A.; DA SILVA BATISTA, CARIN CRISTINA; CERNOCH, PETER; SINCARI, VLADIMIR; JAGER, ALESSANDRO; JAGER, ELIEZER; GIACOMELLI, FERNANDO C.. Role of Membrane Features on the Permeability Behavior of Polymersomes and the Potential Impacts on Drug Encapsulation and Release. Biomacromolecules, v. N/A, p. 10-pg., 2023-04-27. (21/12071-6, 19/06634-8, 19/12944-0)

DE OLIVEIRA, FERNANDO A.; ALBUQUERQUE, LINDOMAR J. C.; CASTRO, CARLOS E.; RISKE, KARIN A.; BELLETTINI, ISMAEL C.; GIACOMELLI, FERNANDO C.. Reduced cytotoxicity of nanomaterials driven by nano-bio interactions: Case study of single protein coronas enveloping polymersomes. COLLOIDS AND SURFACES B-BIOINTERFACES, v. 213, p. 8-pg., 2022-05-01. (19/12944-0, 19/06634-8)

DE CASTRO, CARLOS E.; PANICO, KARINE; STANGHERLIN, LUCAS M.; RIBEIRO, CAROLINE A. S.; DA SILVA, MARIA C. C.; CARNEIRO-RAMOS, MARCELA S.; DAL-BO, ALEXANDRE G.; GIACOMELLI, FERNANDO C.. The Protein Corona Conundrum: Exploring the Advantages and Drawbacks of its Presence around Amphiphilic Nanoparticles. BIOCONJUGATE CHEMISTRY, v. 31, n. 11, p. 2638-2647, NOV 18 2020. (19/06634-8, 15/24686-4)

CERNOCH, PETER; JAGER, ALESSANDRO; CERNOCHOVA, ZULFIYA; SINCARI, VLADIMIR; ALBUQUERQUE, LINDOMAR J. C.; KONEFAL, RAFAL; PAVLOVA, EWA; GIACOMELLI, FERNANDO C.; JAGER, ELIEZER. Engineering of pH-triggered nanoplatforms based on novel poly(2-methyl-2-oxazoline)-b-poly[2-(diisopropylamino)ethyl methacrylate] diblock copolymers with tunable morphologies for biomedical applications. Polymer Chemistry, v. 12, n. 19, p. 2868-2880, MAY 21 2021. (19/06634-8, 16/23844-8, 17/11261-0)

FUENTES-GARCIA, JESUS ANTONIO; ALAVARSE, ALEX CARVALHO; DE CASTRO, CARLOS EDUARDO; GIACOMELLI, FERNANDO CARLOS; IBARRA, MANUEL RICARDO; BONVENT, JEAN-JACQUES; GOYA, GERARDO FABIAN. Sonochemical route for mesoporous silica-coated magnetic nanoparticles towards pH-triggered drug delivery system. JOURNAL OF MATERIALS RESEARCH AND TECHNOLOGY-JMR&T, v. 15, p. 52-67, NOV-DEC 2021. (14/50983-3, 19/06634-8)

DE OLIVEIRA, FERNANDO A.; BATISTA, CARIN C. S.; ALBUQUERQUE, LINDOMAR J. C.; CERNOCH, PETER; STEINHART, MILOS; SINCARI, VLADIMIR; JAGER, ALESSANDRO; JAGER, ELIEZER; GIACOMELLI, FERNANDO C.. Tuning the morphology of block copolymer-based pH-triggered nanoplatforms as driven by changes in molecular weight and protocol of manufacturing. Journal of Colloid and Interface Science, v. 635, p. 11-pg., 2023-04-01. (17/24603-7, 16/23844-8, 19/12944-0, 19/06634-8, 21/12071-6)

DU, HAIQIN; KALEM, SANDRA; HUIN, CECILE; ILLY, NICOLAS; TRESSET, GUILLAUME; GIACOMELLI, FERNANDO CARLOS; GUEGAN, PHILIPPE. Engineering of ion permeable planar membranes and polymersomes based on p-cyclodextrin-cored star copolymers. Journal of Colloid and Interface Science, v. 630, p. 12-pg., 2023-01-15. (21/12071-6, 19/06634-8)

BATISTA, CARIN C. S.; PANICO, KARINE; TROUSIL, JIRI; JANOUSKOVA, OLGA; CASTRO, CARLOS EDUARDO DE; STEPANEK, PETR; GIACOMELLI, FERNANDO C.. Protein coronas coating polymer-stabilized silver nanocolloids attenuate cytotoxicity with minor effects on antimicrobial performance. COLLOIDS AND SURFACES B-BIOINTERFACES, v. 218, p. 11-pg., 2022-08-20. (19/06634-8, 21/12071-6, 17/24603-7, 19/03223-7)