Co-encapsulation of superparamagnetic nanoparticles and doxorubicin in PLGA nanocarriers: Development, characterization and in vitro antitumor efficacy in glioma cells

Abstract

With a very poor prognosis and no clear etiology, glioma is the most aggressive cancer in the brain. Thanks to its versatility, nanomedicine is a promising option to overcome the limitations on chemotherapy imposed by the blood brain barrier (BBB). The objective of this paper was to obtain monitored tumor-targeted therapeutic nanoparticles (NPs). To that end, theranostic surfactant-coated polymer poly-Lactic-co-Glycolic Acid (PLGA) nanoplatform encapsulating doxorubicin hydrochloride (DOX) and superparamagnetic iron oxide NPs (SPIONs) were developed. Different non-ionic surfactants known as BBB crossing enhancers (Tween 80, Brij-35, Pluronic F68 or Vitamin E-TPGS) were used to develop 4 types of theranostic nanoplatforms, which were characterized in terms of size and morphology by DLS, TEM and STEM-HAADF analyses. Moreover, the 3-month stability test, the therapeutic efficacy against different glioma cell lines (U87-MG, 9L/LacZ and patient derived-neuronal stem cells) and the Magnetic Resonance Imaging (MRI) relaxivity were studied. Results showed that the synthesised nanoplatforms were stable at 4 ºC after their lyophilization, being that of paramount importance to ensure a long-term stability in a future in vivo application. Furthermore, the theranostic nanoplatforms were efficient in the in vitro treatment of glioma cells, proving to have imaging efficacy as MRI contrast agents. Our results show an efficient loading of drugs and good value of the relaxivity. Therefore, the efficient theranostic hybrid nanoplatform developed here could be used to perform MRI-guided delivery of hydrophobic drugs.

Applications of superparamagnetic iron oxide nanoparticles in drug and therapeutic delivery, and biotechnological advancements

“…For controlled drug release, 12 nm SPIONs functionalized with poloxamer and heparin and loaded with doxorubicin, were used for 120 h of slow drug release against HeLa cells in vitro [ 38 ]. For the treatment of resistant glioma cells, Luque-Michel et al [ 186 ] obtained spherical polymer platforms made of poly(lactic- co -glycolic acid) containing SPIONs and doxorubicin, which were covered with surfactants. They proved the effectiveness of these platforms in crossing the blood–brain barrier and in MRI of tumors.…”

Theranostics Based on Magnetic Nanoparticles and Polymers: Intelligent Design for Efficient Diagnostics and Therapy

“…Iron oxide NPs modified with PEG, PEI, and Tween 80 (non-ionic surfactant) along with an applied magnetic field allowed for active penetration of the BBB in vivo , suggesting future potential for theranostic delivery through the BBB via Tween-NP conjugates (Huang et al, 2016 ). Other polymer based surfactants such as Brij-35, Pluronic F68, and Vitamin E-TPGS improved passage through BBB allowing for access to brain tumors such as glioblastoma (Luque-Michel et al, 2019 ).…”

“…It is noteworthy that lyophilization was efficiently used for preservation of theranostics with zero effect on physical, chemical, and magnetic properties after prolonged storage (Yang et al, 2017 ; Luque-Michel et al, 2019 ).…”

Nanoparticles for Stem Cell Therapy Bioengineering in Glioma

“…Active targeting is achieved by different methods; a method called ligand targeting works by coating the nanoparticles' surface with one or more ligands such as transferrin, epidermal growth factor (EGF), folic acid, arginyl-glycyl-aspartic tripeptide (RGD) peptide, hyaluronic acid, antibodies, and others (Ruiz-Garcia et al, 2020). These ligands allow NPs to bind specific "receptors" differentially expressed only in certain cancerous blood vessels and/or tumor cells, thus leading to a precise cellular internalization (Maier-Hauff et al, 2007;Kim et al, 2010;Wegscheid et al, 2014;Cheng Y. et al, 2016;Shen et al, 2017;Yu et al, 2017Yu et al, , 2019Hua et al, 2018;Daniel et al, 2019;Denora et al, 2019;Dufort et al, 2019;Kefayat et al, 2019;Kunoh et al, 2019;Luque-Michel et al, 2019;Rego et al, 2019Rego et al, , 2020Ruan et al, TABLE 3 | Advances in the uses of nanoparticles in glioma therapy and diagnosis.…”