Supermagnetic Human Serum Albumin (HSA) Nanoparticles and PLGA-Based Doxorubicin Nanoformulation: A Duet for Selective Nanotherapy

Julia Malinovskaya, Rawan Salami, Marat Valikhov, Veronika Vadekhina, Aleksey Semyonkin, Alevtina Semkina, Maxim Abakumov, Yifat Harel, Esthy Levy, Tzuriel Levin, Rachel Persky, Vladimir Chekhonin, Jean Paul Lellouche, Pavel Melnikov, Svetlana Gelperina

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Abstract

Predicting the ability of nanoparticles (NP) to access the tumor is key to the success of chemotherapy using nanotherapeutics. In the present study, the ability of the dual NP-based theranostic system to accumulate in the tumor was evaluated in vivo using intravital microscopy (IVM) and MRI. The system consisted of model therapeutic doxorubicin-loaded poly(lactide-co-glycolide) NP (Dox-PLGA NP) and novel hybrid Ce3/4+-doped maghemite NP encapsulated within the HSA matrix (hMNP) as a supermagnetic MRI contrasting agent. Both NP types had similar sizes of ~100 nm and negative surface potentials. The level of the hMNP and PLGA NP co-distribution in the same regions of interest (ROI, ~2500 µm2) was assessed by IVM in mice bearing the 4T1-mScarlet murine mammary carcinoma at different intervals between the NP injections. In all cases, both NP types penetrated into the same tumoral/peritumoral regions by neutrophil-assisted extravasation through vascular micro- and macroleakages. The maximum tumor contrasting in MRI scans was obtained 5 h after hMNP injection/1 h after PLGA NP injection; the co-distribution level at this time reached 78%. Together with high contrasting properties of the hMNP, these data indicate that the hMNP and PLGA NPs are suitable theranostic companions. Thus, analysis of the co-distribution level appears to be a useful tool for evaluation of the dual nanoparticle theranostics, whereas assessment of the leakage areas helps to reveal the tumors potentially responsive to nanotherapeutics.

Original languageEnglish
Article number627
JournalInternational Journal of Molecular Sciences
Volume24
Issue number1
DOIs
StatePublished - Jan 2023

Bibliographical note

Publisher Copyright:
© 2022 by the authors.

Keywords

  • 4T1 mScarlet cells
  • 4T1 murine mammary carcinoma
  • EPR effect
  • PLGA nanoparticles
  • hybrid maghemite/human serum albumin nanoparticles
  • intravital microscopy (IVM)
  • magnetic resonance imaging (MRI)

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