Nanoparticles that bind to lipoprotein receptors in the treatment atherosclerosis, acute myocardial infarction, post-heart transplantation status, cancer and endometriosis

• Grant number: 14/03742-0
• Support Opportunities: Research Projects - Thematic Grants
• Start date: November 01, 2015
• End date: January 31, 2021
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Raul Cavalcante Maranhao
• Grantee: Raul Cavalcante Maranhao
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Pesquisadores principais: Edmund Chada Baracat ; Noedir Antônio Groppo Stolf
• Associated researchers: Aleksandra Tiemi Morikawa ; Carmen Guilherme Christiano de Matos Vinagre ; Elaine Rufo Tavares ; Eloisa Silva Dutra de Oliveira Bonfá ; Fatima Rodrigues de Sousa e Freitas ; Gilbert Alexandre Sigal ; Irene de Lourdes Noronha ; José Carlos Nicolau ; Luiz Antonio Machado Cesar ; Maria Carolina Guido ; Priscila Carvalho Melero da Silva ; Raul Dias dos Santos Filho ; Roberto Hegg ; Roger Chammas ; Sérgio Podgaec ; Silvia Regina Graziani ; Wilson Jacob Filho
• Associated research grant(s): 19/22082-5 - Multi-User Equipment approved in grant 2014/03742-0: Liquid Scintilation Counter, AP.EMU; 18/01709-7 - European Atherosclerosis Society - 86th EAS Congress, AR.EXT
• Associated scholarship(s): 17/02549-0 - Remodeling of omega 3 and omega 6 polyunsaturated fatty acids in extracellular vesicles released by Melanoma cells: changed response to radiotherapy?, BP.PD

Abstract

In previous and pioneer studies, we showed that, upon injection in the blood circulation, non-protein lipid nanoemulsions (LDE) with composition resembling low-density lipoprotein (LDL) have the ability to carry chemotherapeutic agents and concentrate them in malignant tumors or inflammation sites. By using LDE as vehicle, toxicity of those drugs was pronouncedly reduced without loss of anti-tumoral action, as showed in cancer patients. In animal models of disease, anti-cancer drugs carried in LDE markedly reduced atherosclerosis lesions, the inflammation of arthritis and graft coronary disease, which opens novel and important therapeutic applications for those drugs. In this project, new LDE-chemo- therapeutic agent preparations will be developed to widen the therapeutic applications of the system. LDE-paclitaxel will be tested in a rat model of acute myocardial infarction; new LDE-drug preparations will be tested in rabbits with heart transplantation to control coronary heart graft disease. In a double-blind, placebo-controled study, the treatment with LDE-paclitaxel on atheroma regression and the inflammatory status will be evaluated in patients with chronic coronary disease. LDE-paclitaxel will be tested in patients with breast, ovary, prostate and lung carcinomas. Intra-tumoral injection of LDE-paclitaxel will be tested in patients with ulcerated breast carcinoma attempting to acquire an effective treatment and in a neo-adjuvant chemotherapeutic scheme (TAC) for breast cancer. Thus, based in solid evidences of previous studies, we intend to continue to develop a wide platform to improve cancer chemotherapy and endow the therapeutics of several degenerative diseases with the weaponry of chemotherapeutic agents, now devoid of toxicity by the association with LDE. LDE will also be used to explore HDL metabolism in aging subjects with or without cardiovascular disease, in the pursuit of novel biomarkers for longevity and healthy aging. (AU)

Scientific publications

(25)

(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)

GUIDO, MARIA C.; MARQUES, ALYNE F.; TAVARES, ELAINE R.; TAVARES DE MELO, MARCELO D.; SALEMI, VERA M. C.; MARANHAO, RAUL C.. The Effects of Diabetes Induction on the Rat Heart: Differences in Oxidative Stress, Inflammatory Cells, and Fibrosis between Subendocardial and Interstitial Myocardial Areas. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2017. (14/03742-0)

SALSOSO, ROCIO; DALCOQUIO, TALIA F.; FURTADO, REMO H. M.; FRANCI, ANDRE; BARBOSA, CARLOS J. D. G.; GENESTRETI, PAULO R. R.; STRUNZ, CELIA M. C.; LIMA, VIVIANE; BARACIOLI, LUCIANO M.; GIUGLIANO, ROBERT P.; et al. Relation of High Lipoprotein (a) Concentrations to Platelet Reactivity in Individuals with and Without Coronary Artery Disease. ADVANCES IN THERAPY, SEP 2020. (14/01021-4, 14/03742-0, 17/26922-2)

DE LIMA, ALINE D.; GUIDO, MARIA C.; TAVARES, ELAINE R.; CARVALHO, PRISCILA O.; MARQUES, ALYNE F.; DE MELO, MARCELO D. T.; SALEMI, VERA M. C.; KALIL-FILHO, ROBERTO; MARANHAO, RAUL C.. The Expression of Lipoprotein Receptors Is Increased in the Infarcted Area After Myocardial Infarction Induced in Rats With Cardiac Dysfunction. LIPIDS, v. 53, n. 2, p. 177-187, FEB 2018. (14/03742-0)

GRAZIANI, SILVIA R.; VITAL, CAROLINA G.; MORIKAWA, ALEKSANDRA T.; VAN EYLL, BRIGITTE M.; FERNANDES JUNIOR, HEZIO J.; KALIL FILHO, ROBERTO; MARANHAO, RAUL C.. Phase II study of paclitaxel associated with lipid core nanoparticles (LDE) as third-line treatment of patients with epithelial ovarian carcinoma. MEDICAL ONCOLOGY, v. 34, n. 9, SEP 2017. (14/03742-0)

DRAGER, LUCIANO F.; TAVONI, THAUANY M.; SILVA, VANESSA M.; SANTOS, RAUL D.; PEDROSA, RODRIGO P.; BORTOLOTTO, LUIZ A.; VINAGRE, CARMEN G.; POLOTSKY, VSEVOLOD Y.; LORENZI-FILHO, GERALDO; MARANHAO, RAUL C.. Obstructive sleep apnea and effects of continuous positive airway pressure on triglyceride-rich lipoprotein metabolism. Journal of Lipid Research, v. 59, n. 6, p. 1027-1033, JUN 2018. (14/03742-0, 12/02953-2)

BUSTOS, SILVINA ODETE; ANTUNES, FERNANDA; RANGEL, MARIA CRISTINA; CHAMMAS, ROGER. Emerging Autophagy Functions Shape the Tumor Microenvironment and Play a Role in Cancer Progression-Implications for Cancer Therapy. FRONTIERS IN ONCOLOGY, v. 10, NOV 25 2020. (15/22814-5, 14/03742-0)

MENEGHINI, BIANCA C.; TAVARES, ELAINE R.; GUIDO, MARIA C.; TAVONI, THAUANY M.; STEFANI, HELIO A.; KALIL-FILHO, ROBERTO; MARANHAO, RAUL C.. Lipid core nanoparticles as vehicle for docetaxel reduces atherosclerotic lesion, inflammation, cell death and proliferation in an atherosclerosis rabbit model. VASCULAR PHARMACOLOGY, v. 115, p. 46-54, APR 2019. (14/03742-0)

PEPINELI, RAFAEL; SANTANA, ALEXANDRE C.; SILVA, FILIPE M. O.; TAVONI, THAUANY M.; STOLF, NOEDIR A. G.; NORONHA, IRENE L.; MARANHAO, RAUL C.. Use of paclitaxel carried in lipid nanoparticles to treat aortic allograft transplantation in rats. Journal of Pharmacy and Pharmacology, v. 73, n. 8, p. 1092-1100, AUG 2021. (14/03742-0)

DE MACEDO RIBEIRO, FLAVIO ROBERTO CAVALLEIRO; RIBEIRO, CAROLINA HEITMANN MARES AZEVEDO; TAVONI, THAUANY MARTINS; DOS SANTOS SARGES, ERICA; FREITAS, FATIMA RODRIGUES; STOLF, NOEDIR ANTONIO GROPPO; KALIL FILHO, ROBERTO; MARANHAO, RAUL CAVALCANTE. Disturbances of the transfer of cholesterol to high-density lipoprotein (HDL) in patients with peripheral artery disease with or without type 2 diabetes mellitus. VASCULAR MEDICINE, v. 26, n. 6, p. 602-607, DEC 2021. (14/03742-0)

OCCHIUTTO, MARCELO L.; PASSOS, THAIS H. M.; FREITAS, FATIMA R.; MARANHAO, RAUL C.; COSTA, VITAL P.. Intraoperative paclitaxel associated with lipid nanoparticles in trabeculectomy. CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY, v. N/A, p. 3-pg., 2023-06-04. (14/03742-0)

VITAL, CAROLINA G.; MARANHAO, RAUL C.; FREITAS, FATIMA R.; VAN EYLL, BRIGITTE M.; GRAZIANI, SILVIA R.. Use of paclitaxel carried in lipid core nanoparticles in patients with late-stage solid cancers with bone metastases: Lack of toxicity and therapeutic benefits. JOURNAL OF BONE ONCOLOGY, v. 34, p. 7-pg., 2022-04-29. (14/03742-0)

ALBUQUERQUE, CAMILA INAGAKI; TAVARES, ELAINE RUFO; GUIDO, MARIA CAROLINA; CARVALHO, PRISCILA OLIVEIRA; TAVONI, THAUANY MARTINS; LOPES, NATALIA MENEZES; SILVA, BRUNA MIRANDA DE OLIVEIRA; JENSEN, LEONARDO; STOLF, NOEDIR ANTONIO GROPPO; MARANHA, RAUL CAVALCANTE. Treatment of rabbits with atherosclerosis induced by cholesterol feeding with daunorubicin associated to a lipid core nanoparticle (LDE). JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, v. 79, p. 10-pg., 2023-01-01. (14/03742-0)

GUIDO, MARIA CAROLINA; LOPES, NATALIA DE MENEZES; ALBUQUERQUE, CAMILA INAGAKI; TAVARES, ELAINE RUFO; JENSEN, LEONARDO; CARVALHO, PRISCILA DE OLIVEIRA; TAVONI, THAUANY MARTINS; DIAS, RICARDO RIBEIRO; PEREIRA, LYGIA DA VEIGA; LAURINDO, FRANCISCO RAFAEL MARTINS; et al. Treatment With Methotrexate Associated With Lipid Core Nanoparticles Prevents Aortic Dilation in a Murine Model of Marfan Syndrome. FRONTIERS IN CARDIOVASCULAR MEDICINE, v. 9, p. 13-pg., 2022-06-10. (14/03742-0)

SILVA, FILIPE M. O.; CARVALHO, PRISCILA C.; COSTALONGA, ELERSON L.; PEPINELI, RAFAEL; MARANHAO, RAUL; NORONHA, IRENE. Use of paclitaxel carried in solid lipid nanoparticles to prevent peritoneal fibrosis in rats. PLoS One, v. 17, n. 5, p. 15-pg., 2022-01-01. (14/03742-0)

GUIDO, MARIA C.; MARQUES, ALYNE F.; TAVARES, ELAINE R.; TAVARES DE MELO, MARCELO D.; SALEMI, VERA M. C.; MARANHAO, RAUL C.. The Effects of Diabetes Induction on the Rat Heart: Differences in Oxidative Stress, Inflammatory Cells, and Fibrosis between Subendocardial and Interstitial Myocardial Areas. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, v. 2017, p. 11-pg., 2017-01-01. (14/03742-0)

DE MACEDO RIBEIRO, FLAVIO ROBERTO CAVALLEIRO; RIBEIRO, CAROLINA HEITMANN MARES AZEVEDO; TAVONI, THAUANY MARTINS; DOS SANTOS SARGES, ERICA; FREITAS, FATIMA RODRIGUES; STOLF, NOEDIR ANTONIO GROPPO; KALIL FILHO, ROBERTO; MARANHAO, RAUL CAVALCANTE. Disturbances of the transfer of cholesterol to high-density lipoprotein (HDL) in patients with peripheral artery disease with or without type 2 diabetes mellitus. VASCULAR MEDICINE, JUN 2021. (14/03742-0)

DE SOUSA ANDRADE, LUCIANA NOGUEIRA; OTAKE, ANDREIA HANADA; BRAGA CARDIM, SILVIA GUEDES; DA SILVA, FELIPE I. LELIS; IKOMA SAKAMOTO, MARIANA MARI; FURUYA, TATIANE KATSUE; UNO, MIYUKI; PASINI, FATIMA SOLANGE; CHAMMAS, ROGER. Extracellular Vesicles Shedding Promotes Melanoma Growth in Response to Chemotherapy. SCIENTIFIC REPORTS, v. 9, OCT 9 2019. (18/01366-2, 14/03742-0)

DAMINELLI, ELAINE N.; FOTAKIS, PANAGIOTIS; MESQUITA, CARLOS H.; MARANHAO, RAUL C.; ZANNIS, VASSILIS I.. Tissue Uptake Mechanisms Involved in the Clearance of Non-Protein Nanoparticles that Mimic LDL Composition: A Study with Knockout and Transgenic Mice. LIPIDS, v. 52, n. 12, p. 991-998, DEC 2017. (14/03742-0)

ALMEIDA, EWIN B.; SANTOS, JULIANA M. B.; PAIXAO, VITORIA; AMARAL, JONATAS B.; FOSTER, ROBERTA; SPERANDIO, ADRIANE; ROSEIRA, TAMARIS; ROSSI, MARCELO; CORDEIRO, TELMA G.; MONTEIRO, FERNANDA R.; et al. L-Glutamine Supplementation Improves the Benefits of Combined-Exercise Training on Oral Redox Balance and Inflammatory Status in Elderly Individuals. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, v. 2020, JAN 22 2020. (12/15165-2, 16/04845-3, 19/14115-0, 14/03742-0, 17/06032-2)

OTAKE, ANDREIA HANADA; SAITO, RENATA DE FREITAS; MARQUES DUARTE, ANA PAULA; RAMOS, ALEXANDRE FERREIRA; CHAMMAS, ROGER. G(D3) ganglioside-enriched extracellular vesicles stimulate melanocyte migration. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, v. 1864, n. 3, p. 422-432, MAR 2019. (14/03742-0, 98/14247-6)

SOARES, ALEXANDRE A. S.; TAVONI, THAUANY M.; DE FARIA, ELIANE C.; REMALAY, ALAN T.; MARANHAO, RAUL C.; SPOSITO, ANDREI C.; GRP, BRASILIA HEART STUDY. HDL acceptor capacities for cholesterol efflux from macrophages and lipid transfer are both acutely reduced after myocardial infarction. Clinica Chimica Acta, v. 478, p. 51-56, MAR 2018. (14/03742-0)

BACHI, ANDRE L. L.; BARROS, MARCELO P.; VIEIRA, RODOLFO P.; ROCHA, GISLENE A.; DE ANDRADE, PAULA B. M.; VICTORINO, ANGELICA B.; RAMOS, LUIZ R.; GRAVINA, CLAUDIA F.; LOPES, JOSE D.; VAISBERG, MAURO; et al. Combined Exercise Training Performed by Elderly Women Reduces Redox Indexes and Proinflammatory Cytokines Related to Atherogenesis. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, v. 2019, AUG 5 2019. (12/15165-2, 17/06032-2, 16/04845-3, 14/03742-0)

CAMARGO DE OLIVEIRA, WILSON PASCOALINO; TAVONI, THAUANY MARTINS; FREITAS, FATIMA RODRIGUES; OLIVEIRA SILVA, BRUNA MIRANDA; MARANHAO, RAUL CAVALCANTE. Lipid transfers to HDL are diminished in long-term bedridden patients: association with low HDL-cholesterol and increased inflammatory markers. LIPIDS, v. 52, n. 8, p. 703-709, AUG 2017. (14/03742-0)

LANG, MARIA G.; VINAGRE, CARMEN G. C.; BONFA, ELOISA; FREITAS, FATIMA R.; PASOTO, SANDRA G.; BRITO, TATIANE S.; SEGURO, LUCIANA P. C.; MARANHAO, RAUL C.; BORBA, EDUARDO F.. Hydroxychloroquine increased cholesterol transfer to high-density lipoprotein in systemic lupus erythematosus: A possible mechanism for the reversal of atherosclerosis in the disease. Lupus, v. 31, n. 6, p. 7-pg., 2022-03-25. (15/03756-4, 17/14352-7, 14/03742-0)

SALSOSO, ROCIO; DALCOQUIO, TALIA F.; FURTADO, REMO H. M.; FRANCI, ANDRE; BARBOSA, CARLOS J. D. G.; GENESTRETI, PAULO R. R.; STRUNZ, CELIA M. C.; LIMA, VIVIANE; BARACIOLI, LUCIANO M.; GIUGLIANO, ROBERT P.; et al. Relation of High Lipoprotein (a) Concentrations to Platelet Reactivity in Individuals with and Without Coronary Artery Disease. ADVANCES IN THERAPY, v. 37, n. 11, p. 17-pg., 2020-09-05. (14/03742-0, 17/26922-2, 14/01021-4)