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Uptake of lipid core nanoparticles by fragments of tissues collected during cerebral tumor excision surgeries: hypotheses for use in drug targeting therapy

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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 14C-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.

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Acknowledgements

This study was supported by the São Paulo Research Support Foundation (FAPESP), National Council for Scientific and Technological Development (CNPq), and the National Institute of Science and Technology Complex Fluids (INCT-FCx). Dr. Maranhão holds an A-1 Research Carrier Award from CNPq.

Funding

This study was supported by the São Paulo Research Support Foundation (FAPESP, grant number 2014/03742–0, Brazil), National Council for Scientific and Technological Development (CNPq, grant 431290/2016–4, Brasilia, Brazil).

Author information

Authors and Affiliations

  1. Servico de Cirurgia, Nucleo de Pesquisas em Neurooncologia, Hospital Universitario Joao de Barros Barreto, Universidade Federal do Para, Belem, Para, Brazil

    Edmundo Luís Rodrigues Pereira, João Pojucan Lobo Tavares & Natalia Megumi Morikawa

  2. Centro Universitario Metropolitano da Amazonia – UNIFAMAZ, Belem, Para, Brazil

    Danielle Cristinne Azevedo Feio

  3. Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, Brazil

    Debora Fernandes Deus, Carolina Graziani Vital, Elaine Rufo Tavares & Raul Cavalcante Maranhão

  4. Faculdade de Ciencias Farmaceuticas, Universidade de Sao Paulo, São Paulo, Brazil

    Raul Cavalcante Maranhão

  5. Instituto Nacional de Ciencias e Tecnologia em Fluidos Complexos (INCT-FCx), São Paulo, São Paulo, Brazil

    Raul Cavalcante Maranhão

  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

    Raul Cavalcante Maranhão

Authors
  1. Edmundo Luís Rodrigues Pereira
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  2. Danielle Cristinne Azevedo Feio
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  5. Debora Fernandes Deus
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  6. Carolina Graziani Vital
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  7. Elaine Rufo Tavares
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  8. Raul Cavalcante Maranhão
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Contributions

Conceptualization and project administration: ELRP and RCM; methodology: DFD, ELRP, and RCM; formal analysis: ELRP and RCM; investigation: ELRP, DCAF, JPLT, and NMM; data curation: ELRP, DCAF, DFD, and RCM; writing—original draft preparation: ERT, CGV, ELRP, and RCM; writing—review and editing: ERT and CGV; supervision and funding acquisition: RCM.

Corresponding author

Correspondence to Raul Cavalcante Maranhão.

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Competing interests

The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

This study was approved by the Ethics Committee of the Federal University of Pará (CAAE 98117312.2.0000.0017). All subjects signed informed consent form in accordance with the Declaration of Helsinki.

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Pereira, E.L.R., Feio, D.C.A., Tavares, J.P.L. et al. Uptake of lipid core nanoparticles by fragments of tissues collected during cerebral tumor excision surgeries: hypotheses for use in drug targeting therapy. J Neurooncol 158, 413–421 (2022). https://doi.org/10.1007/s11060-022-04028-1

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