Nose-to-Brain Delivery of Cancer-Targeting Paclitaxel-Loaded Nanoparticles Potentiates Antitumor Effects in Malignant Glioblastoma

Abstract

Glioblastoma multiforme (GBM) is an aggressive tumor with no curative treatment. The tumor recurrence after resection often requires chemotherapy or radiation to delay the infiltration of tumor remnants. Intracerebral chemotherapies are preferentially being used to prevent tumor regrowth, but treatments remain unsuccessful because of the poor drug distribution in the brain. In this study, we investigated the therapeutic efficacy of cancer-targeting arginyl-glycyl-aspartic tripeptide (RGD) conjugated paclitaxel (PTX)-loaded nanoparticles (NPs) against GBM by nose-to-brain delivery. Our results demonstrated that RGD-modified PTX-loaded NPs showed cancer-specific delivery and enhanced anticancer effects in vivo. The intranasal (IN) inoculation of RGD-PTX-loaded NPs effectively controls the tumor burden (75 ± 12% reduction) by inducing apoptosis and/or inhibiting cancer cell proliferation without affecting the G0 stage of normal brain cells. Our data provide therapeutic evidence supporting the use of intranasally delivered cancer-targeted PTX-loaded NPs for GBM therapy.

Ultrasound-mediated delivery of RGD-conjugated nanobubbles loaded with fingolimod and superparamagnetic iron oxide nanoparticles: targeting hepatocellular carcinoma and enhancing magnetic resonance imaging

“…44 A number of studies demonstrated that the RGD modied nano-drug delivery systems could improve the active targeting efficiency of tumor cells. [45][46][47][48] Thereby, the ultrasound irritation could mediate the drug-loaded NBs to be more easily internalized into the cells, and the prepared RGD-modied NBs could further improve cellular uptake and increase the delivery efficiency of FTY720. The cellular uptake efficiency of the FTY720@SPION/PFP/NB or FTY720@SPION/PFP/RGD-NB was also evaluated by observing MRI T2-weighted imaging (T2WI) and by measuring T 2 value of HepG2 cells when incubated with different nanoparticles using a clinical 1.5T MRI scanner.…”

Nanoparticles for Stem Cell Therapy Bioengineering in Glioma

“…• In vivo: PLGA-NP (Sousa et al, 2019;Ye et al, 2019;Caban-Toktas et al, 2020;Chung et al, 2020), RGD-NP (Ullah et al, 2020), oleic acid NP (Wang H. et al, 2020) • In vitro only: PLGA-NP (Luque-Michel et al, 2019;Ferreira et al, 2020;Roberts et al, 2020), ethyl arachidate (TPLN) (Alves et al, 2020), FONP (Daniel et al, 2019), pSiNPs…”

“…2019; Shi et al, 2019;Sousa et al, 2019;Ye et al, 2019;Zhang et al, 2019;Zhao et al, 2019;ZhuGe et al, 2019;Alves et al, 2020;Caban-Toktas et al, 2020;Chung et al, 2020;Ferreira et al, 2020;Kazmi et al, 2020;Liang et al, 2020;Martinez-Rovira et al, 2020;Meng et al, 2020;Roberts et al, 2020;Ullah et al, 2020;Wang H. et al, 2020;Wang X. et al, 2020;Xu et al, 2020;Zhu et al, 2020; see Table 3 for examples of ligand targeting in glioma research). Another active targeting method to increase functional specificity of NPs that are used as gene delivery systems is the transcriptional targeting, which can occur at a transcriptional or posttranscriptional level (Golombek et al, 2018).…”

“…Here, the delivered gene includes a tumor-specific promoter (highly functional only in cancer cells), which will secure a well-localized expression of the transgene, limited to occur only inside the cancer cells of interest. Posttranscriptional regulations of the product encoded by the exogenously delivered gene are achieved by controlling RNA splicing, RNA stability, and initiation of the RNA translation once it is present in the cancer cell (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, 2017;Hua et al, 2018;Daniel et al, 2019;Denora et al, 2019;Dufort et al, 2019;Kunoh et al, 2019;Luque-Michel et al, 2019;Ruan et al, 2019;Rego et al, 2019Rego et al, , 2020Shi et al, 2019;Sousa et al, 2019;Ye et al, 2019;Zhang et al, 2019;Zhao et al, 2019;ZhuGe et al, 2019;Alves et al, 2020;Caban-Toktas et al, 2020;Chung et al, 2020;Ferreira et al, 2020;Kazmi et al, 2020;Liang et al, 2020;Martinez-Rovira et al, 2020;Meng et al, 2020;Roberts et al, 2020;Ullah et al, 2020;Wang H. et al, 2020;Wang X. et al, 2020;Xu et al, 2020;Zhu et al, 2020).…”

Microfluidic-assisted preparation of RGD-decorated nanoparticles: exploring integrin-facilitated uptake in cancer cell lines

“…Over the last decade, attention has specifically focused on peptides capable of targeting two of the most overexpressed heterodimers in cancer, i.e. α v β 3 for glioblastoma or ovarian cancers 11 , 17 , 20 , and α 5 β 1 for ovarian and lung cancers 17 , 21 , providing the means for the potential targeted delivery of classical chemotherapeutic agents 22 – 25 , nucleic acids 26 , 27 , proteins 28 , imaging agents 29 , 30 , or a combination of these 28 , 31 , 32 to malignant cells.…”