Vol.:(0123456789) 1 3
Journal of Neuro-Oncology (2022) 158:413–421
https://doi.org/10.1007/s11060-022-04028-1
RESEARCH
Uptake of lipid core nanoparticles by fragments of tissues collected
during cerebral tumor excision surgeries: hypotheses for use in drug
targeting therapy
Edmundo Luís Rodrigues Pereira
1
· Danielle Cristinne Azevedo Feio
2
· João Pojucan Lobo Tavares
1
·
Natalia Megumi Morikawa
1
· Debora Fernandes Deus
3
· Carolina Graziani Vital
3
· Elaine Rufo Tavares
3
·
Raul Cavalcante Maranhão
3,4,5,6
Received: 25 March 2022 / Accepted: 5 May 2022 / Published online: 25 May 2022
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022
Abstract
Purpose Malignant cerebral tumors have poor prognosis and the blood–brain barrier is a major hindrance for most drugs to
reach those tumors. Lipid nanoparticles (LDE) that bind to lipoprotein receptors may carry anticancer drugs and penetrate
the cells through those receptors that are overexpressed in gliomas. The aim was to investigate the in vivo uptake of LDE
by human cerebral tumors.
Methods Twelve consecutive patients (4 with glioblastomas, 1 meduloblastoma, 1 primary lymphoma, 2 with non-cerebral
metastases and 4 with benign tumors) scheduled for tumor excision surgery were injected intravenously, 12 h before surgery,
with LDE labeled
14
C-cholesterol oleate. Fragments of tumors and of normal head tissues (muscle, periosteum, dura mater)
discarded by the surgeon were submitted to lipid extraction and radioactive counting.
Results Tumor LDE uptake (range: 10–283 d.p.m./g of tissue) was not lower than that of normal tissues (range: 20–263
d.p.m./g). Malignant tumor uptake was threefold greater than benign tumor uptake (140 ± 93 vs 46 ± 18 d.p.m./g, p < 0.05).
Results show that LDE can concentrate in brain malignant tumors and may be used to carry drugs directed against those
tumors.
Conclusion As LDE was previously shown to markedly decrease drug toxicity this new therapeutic strategy should be tested
in future trials.
Keywords Nanoemulsions · Solid lipid nanoparticles · Glioma treatment · LDL-receptor and cancer · Blood–brain barrier
Introduction
Despite the great advances in chemotherapy, immunother-
apy and targeted therapy for cancer, little progress has been
achieved in the prognosis of malignant brain tumors, such
as gliomas, that account for more than 80% of the brain
tumors. In respect to glioblastoma multiforme, which is the
most common type of gliomas, the most prevalent malig-
nant primary brain tumor in adult individuals and the most
aggressive, prognosis remains extremely poor. The expected
survival of glioblastoma patients has not been improved for
decades and is less than 1 1/2 year after the excision surgery
* Raul Cavalcante Maranhão
ramarans@usp.br
1
Servico de Cirurgia, Nucleo de Pesquisas em
Neurooncologia, Hospital Universitario Joao de Barros
Barreto, Universidade Federal do Para, Belem, Para, Brazil
2
Centro Universitario Metropolitano da Amazonia –
UNIFAMAZ, Belem, Para, Brazil
3
Instituto do Coracao (InCor), Hospital das Clinicas
HCFMUSP, Faculdade de Medicina, Universidade de Sao
Paulo, São Paulo, Brazil
4
Faculdade de Ciencias Farmaceuticas, Universidade de Sao
Paulo, São Paulo, Brazil
5
Instituto Nacional de Ciencias e Tecnologia em Fluidos
Complexos (INCT-FCx), São Paulo, São Paulo, Brazil
6
Laboratório de Metabolismo e Lípides, Instituto do Coração
(InCor) do Hospital das Clínicas da Faculdade de Medicina
da Universidade de São Paulo (HCFMUSP), Av. Dr. Enéas
de Carvalho Aguiar, 44, bloco 2, 1º subsolo, São Paulo, SP,
Brazil