Stealth nanoparticles in oncology: Facing the PEG dilemma

Zalba, Sara; Hagen, Timo L.M. ten; Burgui, Carmen; Garrido, María J.

doi:10.1016/j.jconrel.2022.09.002

Cited by 73 publications

(36 citation statements)

References 197 publications

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“…We revealed that GBM is characterized by a dramatically reduced intranasal delivery of liposomes to the brain. This can be explained by a decrease in the MLVs network and the reduced outflow of the CSF in mice with GBM that was reported in other investigations [63][64][65][66][67]. Hu et al demonstrate that the dorsal MLVs undergo extensive remodeling in mice with GL261 glioma that is accompanied by changes in the gene controlling lymphatic remodeling, fluid drainage, inflammatory, and immunological responses [57].…”

Section: Discussionmentioning

confidence: 73%

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Intranasal Delivery of Liposomes to Glioblastoma by Photostimulation of the Lymphatic System

Semyachkina-Glushkovskaya

Shirokov

Blokhina

et al. 2022

Pharmaceutics

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The blood–brain barrier (BBB) limits the delivery of majority of cancer drugs and thereby complicates brain tumor treatment. The nasal-brain-lymphatic system is discussed as a pathway for brain drug delivery overcoming the BBB. However, in most cases, this method is not sufficient to achieve a therapeutic effect due to brain drug delivery in a short distance. Therefore, it is necessary to develop technologies to overcome the obstacles facing nose-to-brain delivery of promising pharmaceuticals. In this study, we clearly demonstrate intranasal delivery of liposomes to the mouse brain reaching glioblastoma (GBM). In the experiments with ablation of the meningeal lymphatic network, we report an important role of meningeal pathway for intranasal delivery of liposomes to the brain. Our data revealed that GBM is characterized by a dramatic reduction of intranasal delivery of liposomes to the brain that was significantly improved by near-infrared (1267 nm) photostimulation of the lymphatic vessels in the area of the cribriform plate and the meninges. These results open new perspectives for non-invasive improvement of efficiency of intranasal delivery of cancer drugs to the brain tissues using nanocarriers and near-infrared laser-based therapeutic devices, which are commercially available and widely used in clinical practice.

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Section: Discussionmentioning

confidence: 73%

“…Later, instead of glycolipids, less expensive lipid conjugates with polyethylene glycol evolved as protecting components for liposomal formulations. Although, well-known pegylation of drug delivery systems often lead to problems associated with immunity against pegylation (reviewed in [ 64 ]).…”

Section: Discussionmentioning

confidence: 99%

Intranasal Delivery of Liposomes to Glioblastoma by Photostimulation of the Lymphatic System

Semyachkina-Glushkovskaya

Shirokov

Blokhina

et al. 2022

Pharmaceutics

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“…To overcome this problem, various polymers, in particular poly(ethylene glycol) (PEG), have been used to cover the surface of these nanocarriers forming a hydrophilic layer that allows the delay of removal. These advantages contrast with some drawbacks such as the difficulty of interacting with cell membranes and the development of immunological reactions, conforming to the known ‘PEG dilemma’ 14 …”

Section: Introductionmentioning

confidence: 96%

“…These advantages contrast with some drawbacks such as the difficulty of interacting with cell membranes and the development of immunological reactions, conforming to the known 'PEG dilemma'. 14 Another challenge is the controlled release of a drug from a DDS. Drugs adsorbed to the surface of the carrier system are subject to a premature release ('burst release') which can cause adverse effects in other tissues.…”

Section: Introductionmentioning

confidence: 99%

Stimuli‐accelerated polymeric drug delivery systems

Rust

Jung

Langer

et al. 2022

Polymer International

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The controlled delivery of active pharmaceutical ingredients to the site of disease represents a major challenge in drug therapy. Particularly when drugs have to be transported across biological barriers, suitable drug delivery systems are of importance. In recent years responsive delivery systems have been developed which enable a controlled drug release depending on internal or external stimuli such as changes in pH, redox environment or light and temperature. In some studies delivery systems with reactivity against two different stimuli were established either to enhance the response by synergies of the stimuli or to broaden the window of possible trigger events. In the present review numerous exciting developments of pH‐, light‐ and redox‐cleavable polymers suitable for the preparation of smart delivery systems are described. The review discusses the different stimuli that can be used for a controlled drug release of polymer‐based delivery systems. It puts a focus on the different polymers described for the preparation of stimuli‐sensitive systems, their preparation techniques as well as their stimuli‐responsive degradation. © 2022 The Authors. Polymer International published by John Wiley & Sons Ltd on behalf of Society of Industrial Chemistry.

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“…Among these, PEGylation is a mature technology developed for stealthy drug delivery to impede liver clearance after surface modification by poly(ethylene glycol) (PEG) [13][14][15] . Although PEGylation renders nanoparticles stealthy and hard to be captured by macrophages [16][17][18] , it causes another trouble that is restrained binding and limited internalization by tumor cells 19,20 . Because modification of nanoparticles leads similar uptake tendency for macrophages and tumor cells, contradiction always exists between liver clearance and tumor cellular internalization.…”

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confidence: 99%

Mechano-boosting nanomedicine antitumour efficacy by blocking the reticuloendothelial system with stiff nanogels

Zhu

Zeng

et al. 2023

Nat Commun

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Nanomedicine has been developed for cancer therapy over several decades, while rapid clearance from blood circulation by reticuloendothelial system (RES) severely limits nanomedicine antitumour efficacy. We design a series of nanogels with distinctive stiffness and investigate how nanogel mechanical properties could be leveraged to overcome RES. Stiff nanogels are injected preferentially to abrogate uptake capacity of macrophages and temporarily block RES, relying on inhibition of clathrin and prolonged liver retention. Afterwards, soft nanogels deliver doxorubicin (DOX) with excellent efficiency, reflected in high tumour accumulation, deep tumour penetration and outstanding antitumour efficacy. In this work, we combine the advantage of stiff nanogels in RES-blockade with the superiority of soft nanogels in drug delivery leads to the optimum tumour inhibition effect, which is defined as mechano-boosting antitumour strategy. Clinical implications of stiffness-dependent RES-blockade are also confirmed by promoting antitumour efficacy of commercialized nanomedicines, such as Doxil and Abraxane.

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Stealth nanoparticles in oncology: Facing the PEG dilemma

Cited by 73 publications

References 197 publications

Intranasal Delivery of Liposomes to Glioblastoma by Photostimulation of the Lymphatic System

Intranasal Delivery of Liposomes to Glioblastoma by Photostimulation of the Lymphatic System

Stimuli‐accelerated polymeric drug delivery systems

Mechano-boosting nanomedicine antitumour efficacy by blocking the reticuloendothelial system with stiff nanogels

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