Preprint Article Version 1 This version is not peer-reviewed

Chemotherapeutic Drug Functionalized Nanoparticles are Beneficial When Treating Breast Cancer Via Magnetic Hyperthermia

Version 1 : Received: 31 August 2018 / Approved: 28 September 2018 / Online: 28 September 2018 (13:29:53 CEST)

How to cite: Piehler, S.; Dähring, H.; Grandke, J.; Göring, J.; Couleaud, P.; Aires, A.; Cortajarena, A.L.; Courty, J.; Latorre, A.; Somoza, Á.; Miranda, R.; Hilger, I. Chemotherapeutic Drug Functionalized Nanoparticles are Beneficial When Treating Breast Cancer Via Magnetic Hyperthermia. Preprints 2018, 2018090569 (doi: 10.20944/preprints201809.0569.v1). Piehler, S.; Dähring, H.; Grandke, J.; Göring, J.; Couleaud, P.; Aires, A.; Cortajarena, A.L.; Courty, J.; Latorre, A.; Somoza, Á.; Miranda, R.; Hilger, I. Chemotherapeutic Drug Functionalized Nanoparticles are Beneficial When Treating Breast Cancer Via Magnetic Hyperthermia. Preprints 2018, 2018090569 (doi: 10.20944/preprints201809.0569.v1).

Abstract

Doxorubicin (DOX) is a frequently used chemotherapeutic drug for breast cancer, but its site specificity and local internalization into tumor cells is rather low. In this paper we conjugated magnetic nanoparticles (MNPs) with DOX and/or a pseudopeptide NucAnt (N6L) as modality to enhance DOX-induced antitumor effects in breast cancer cells (BT474). In this context, we determined cellular uptake of MNP formulations, analyzed cell viability and expression of apoptotic and cell cycle proteins after magnetic hyperthermia (43°C, 1 h) in vivo and in vitro. We have shown that i) the presence of N6L on the surface of DOX-functionalized MNPs increases their internalization into a target cells and potentiates the cytotoxic potential of the anticancer drug, ii) in combination with hyperthermia, DOX functionalized MNPs influence the expression of apoptotic and cell cycle proteins, and also favors tumor regression in vivo. Our data show that intratumoral application of DOX coupled MNPs is able to overcome biological barriers to chemotherapeutic drugs, enabling them to penetrate into the target cells. Combined with hyperthermia these MNPs can be an effective method in enhancing the localised delivery and penetration of DOX into breast cancer cells.

Subject Areas

magnetic hyperthermia, magnetic nanoparticles (MNP), doxorubicin (DOX), NucAnt (N6L), breast cancer, mouse model

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