Brain Targeting by Liposome–Biomolecular Corona Boosts Anticancer Efficacy of Temozolomide in Glioblastoma Cells

Arcella, Antonietta; Palchetti, Sara; Digiacomo, Luca; Pozzi, Daniela; Capriotti, Anna Laura; Frati, Luigi; Oliva, Maria Antonietta; Tsaouli, Georgia; Rota, Rossella; Screpanti, Isabella; Mahmoudi, Morteza; Caracciolo, Giulio

doi:10.1021/acschemneuro.8b00339

Cited by 58 publications

(42 citation statements)

References 68 publications

(136 reference statements)

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“…In another study, temozolomide‐loaded cationic liposomes were coated with a corona of plasma proteins with natural affinity toward receptors overexpressed in the BBB. These cationic liposomes with layers of biomolecular corona demonstrated high uptake in human umbilical vein endothelial cells in an in vitro model of the BBB and increased temozolomide anticancer efficacy in the U‐87 MG cell line (Arcella et al, ).…”

Section: Lipid‐based Nanosystemsmentioning

confidence: 99%

Immunoengineering in glioblastoma imaging and therapy

Zanganeh

Georgala

Corbo

et al. 2019

WIREs Nanomed Nanobiotechnol

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Patients diagnosed with glioblastoma have poor prognosis. Conventional treatment strategies such as surgery, chemotherapy, and radiation therapy demonstrated limited clinical success and have considerable side effects on healthy tissues. A central challenge in treating brain tumors is the poor permeability of the blood–brain barrier (BBB) to therapeutics. Recently, various methods based on immunotherapy and nanotechnology have demonstrated potential in addressing these obstacles by enabling precise targeting of brain tumors to minimize adverse effects, while increasing targeted drug delivery across the BBB. In addition to treating the tumors, these approaches may be used in conjunction with imaging modalities, such as magnetic resonance imaging and positron emission tomography to enhance the prognosis procedures. This review aims to provide mechanistic understanding of immune system regulation in the central nervous system and the benefits of nanoparticles in the prognosis of brain tumors. This article is characterized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Nanotechnology Approaches to Biology > Cells at the Nanoscale Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

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Section: Lipid‐based Nanosystemsmentioning

confidence: 99%

Immunoengineering in glioblastoma imaging and therapy

Zanganeh

Georgala

Corbo

et al. 2019

WIREs Nanomed Nanobiotechnol

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“…Recent studies showed that SR-BI and LDLR are overexpressed in pancreatic cancer, thus representing good targets of Apolipoprotein-enriched coronas [49,50]. Liposomal formulations were ranked for their PC-based targeting ability by calculating the total abundance of PCFs [51].…”

Section: Resultsmentioning

confidence: 99%

Protein Corona Fingerprints of Liposomes: New Opportunities for Targeted Drug Delivery and Early Detection in Pancreatic Cancer

et al. 2019

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Pancreatic ductal adenocarcinoma (PDAC) is the fourth cause of cancer-related mortality in the Western world and is envisaged to become the second cause by 2030. Although our knowledge about the molecular biology of PDAC is continuously increasing, this progress has not been translated into better patients’ outcome. Liposomes have been used to circumvent concerns associated with the low efficiency of anticancer drugs such as severe side effects and damage of healthy tissues, but they have not resulted in improved efficacy as yet. Recently, the concept is emerging that the limited success of liposomal drugs in clinical practice is due to our poor knowledge of the nano–bio interactions experienced by liposomes in vivo. After systemic administration, lipid vesicles are covered by plasma proteins forming a biomolecular coating, referred to as the protein corona (PC). Recent studies have clarified that just a minor fraction of the hundreds of bound plasma proteins, referred to as “PC fingerprints” (PCFs), enhance liposome association with cancer cells, triggering efficient particle internalization. In this study, we synthesized a library of 10 liposomal formulations with systematic changes in lipid composition and exposed them to human plasma (HP). Size, zeta-potential, and corona composition of the resulting liposome–protein complexes were thoroughly characterized by dynamic light scattering (DLS), micro-electrophoresis, and nano-liquid chromatography tandem mass spectrometry (nano-LC MS/MS). According to the recent literature, enrichment in PCFs was used to predict the targeting ability of synthesized liposomal formulations. Here we show that the predicted targeting capability of liposome–protein complexes clearly correlate with cellular uptake in pancreatic adenocarcinoma (PANC-1) and insulinoma (INS-1) cells as quantified by flow-assisted cell sorting (FACS). Of note, cellular uptake of the liposomal formulation with the highest abundance of PCFs was much larger than that of Onivyde®, an Irinotecan liposomal drug approved by the Food and Drug Administration in 2015 for the treatment of metastatic PDAC. Given the urgent need of efficient nanocarriers for the treatment of PDAC, we envision that our results will pave the way for the development of more efficient PC-based targeted nanomaterials. Here we also show that some BCs are enriched with plasma proteins that are associated with the onset and progression of PDAC (e.g., sex hormone-binding globulin, Ficolin-3, plasma protease C1 inhibitor, etc.). This could open the intriguing possibility to identify novel biomarkers.

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“…13,51,52 Different types of cells have been studied for this effect including macrophages, fibroblasts, osteoblasts, and HeLa, neuroblastoma and ovarian cancer cells. 44,51,[53][54][55][56][57][58][59] Since corona formation may affect MNP targeting and drug delivery, this phenomenon provides another rationale for laboratory modeling (such as our own), prior to resource-intense in vivo studies. The MBs studied here have been reported to rotate and display translational movement through serum and even blood, 10,11 fluid environments shown to generate a corona.…”

Section: Discussionmentioning

confidence: 99%

<p>Rotating Magnetic Nanoparticle Clusters as Microdevices for Drug Delivery</p>

Willis¹,

Pernal²,

Gaertner³

et al. 2020

IJN

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Background: Magnetic nanoparticles (MNPs) hold promise for enhancing delivery of therapeutic agents, either through direct binding or by functioning as miniature propellers. Fluid-filled conduits and reservoirs within the body offer avenues for MNP-enhanced drug delivery. MNP clusters can be rotated and moved across surfaces at clinically relevant distances in response to a rotating magnet. Limited data are available regarding issues affecting MNP delivery by this mechanism, such as adhesion to a cellular wall. Research reported here was initiated to better understand the fundamental principles important for successful implementation of rotational magnetic drug targeting (rMDT). Methods: Translational movements of four different iron oxide MNPs were tested, in response to rotation (3 Hz) of a neodymium-boron-iron permanent magnet. MNP clusters moved along biomimetic channels of a custom-made acrylic tray, by surface walking. The effects of different distances and cellular coatings on MNP velocity were analyzed using videography. Dyes (as drug surrogates) and the drug etoposide were transported by rotating MNPs along channels over a 10 cm distance. Results: MNP translational velocities could be predicted from magnetic separation times. Changes in distance or orientation from the magnet produced alterations in MNP velocities. Mean velocities of the fastest MNPs over HeLa, U251, U87, and E297 cells were 0.24 ± 0.02, 0.26 ± 0.02, 0.28 ± 0.01, and 0.18 ± 0.03 cm/sec, respectively. U138 cells showed marked MNP adherence and an 87.1% velocity reduction at 5.5 cm along the channel. Dye delivery helped visualize the effects of MNPs as microdevices for drug delivery. Dye delivery by MNP clusters was 21.7 times faster than by diffusion. MNPs successfully accelerated etoposide delivery, with retention of chemotherapeutic effect. Conclusion: The in vitro system described here facilitates side-by-side comparisons of drug delivery by rotating MNP clusters, on a human scale. Such microdevices have the potential for augmenting drug delivery in a variety of clinical settings, as proposed.

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Brain Targeting by Liposome–Biomolecular Corona Boosts Anticancer Efficacy of Temozolomide in Glioblastoma Cells

Cited by 58 publications

References 68 publications

Immunoengineering in glioblastoma imaging and therapy

Immunoengineering in glioblastoma imaging and therapy

Protein Corona Fingerprints of Liposomes: New Opportunities for Targeted Drug Delivery and Early Detection in Pancreatic Cancer

<p>Rotating Magnetic Nanoparticle Clusters as Microdevices for Drug Delivery</p>

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