Controlling Cellular Uptake by Surface Chemistry, Size, and Surface Topology at the Nanoscale

Massignani, Marzia; LoPresti, Caterina; Blanazs, Adam; Madsen, Jeppe; Armes, Steven P.; Lewis, Andrew L.; Battaglia, Giuseppe

doi:10.1002/smll.200900578

Cited by 216 publications

(279 citation statements)

References 31 publications

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“…Furthermore, we have demonstrated (31)(32)(33)(34) that, when two different copolymers are used to form one polymersome, the resulting membrane segregates laterally into patterns whose topology is strictly controlled by the molar ratio of the two copolymers and eventually coarsen into two separate domains forming asymmetric polymersomes (35). Here, we exploit this asymmetry to achieve propulsion at the nanoscale.…”

Section: Introductionmentioning

confidence: 99%

Chemotactic synthetic vesicles: design and applications in blood brain barrier crossing

Joseph

Contini

Cecchin

et al. 2016

Preprint

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114

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In recent years, scientists have created artificial microscopic and nanoscopic self-propelling particles, often referred to as nano-or microswimmers, capable of mimicking biological locomotion and taxis. This active diffusion enables the engineering of complex operations that so far have not been possible at the micro-and nanoscale. One of the most promising tasks is the ability to engineer nanocarriers that can autonomously navigate within tissues and organs, accessing nearly every site of the human body guided by endogenous chemical gradients. We report a fully synthetic, organic, nanoscopic system that exhibits attractive chemotaxis driven by enzymatic conversion of glucose. We achieve this by encapsulating glucose oxidase alone or in combination with catalase into nanoscopic and biocompatible asymmetric polymer vesicles (known as polymersomes). We show that these vesicles self-propel in response to an external gradient of glucose by inducing a slip velocity on their surface, which makes them move in an extremely sensitive way toward higher-concentration regions. We finally demonstrate that the chemotactic behavior of these nanoswimmers, in combination with LRP-1 (low-density lipoprotein receptor-related protein 1) targeting, enables a fourfold increase in penetration to the brain compared to nonchemotactic systems.

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Section: Introductionmentioning

confidence: 99%

Chemotactic synthetic vesicles: design and applications in blood brain barrier crossing

Joseph

Contini

Cecchin

et al. 2016

Preprint

Self Cite

114

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“…Here we investigate the use of polymersomes comprised of the amphiphilic block copolymer poly 2-(methacryloyloxy)ethyl phosphorylcholine (PMPC) coupled with the pH-sensitive copolymer poly 2-(diisopropylamino)ethyl methacrylate (PDPA) for anti-cancer drug delivery. PMPC-PDPA polymersomes have been demonstrated to be internalised via endocytosis 19 and dissociate within the low pH in the endosomal compartment, releasing their cargo into the cell cytosol 20 . Indeed, polymersomes have been used to deliver DNA, siRNA, proteins and antibodies into live cells 21, 22, 23, 24. The membrane-enclosed vesicular structure of polymersomes enables both hydrophilic and hydrophobic materials to be encapsulated within their aqueous core and the hydrophobic membrane respectively 25 .…”

Section: Introductionmentioning

confidence: 99%

Polymersome-Mediated Delivery of Combination Anticancer Therapy to Head and Neck Cancer Cells: 2D and 3D in Vitro Evaluation

et al. 2014

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Polymersomes have the potential to encapsulate and deliver chemotherapeutic drugs into tumour cells, reducing off-target toxicity that often compromises anti-cancer treatment. Here we assess the ability of the pH-sensitive poly 2-(methacryloyloxy)ethyl phosphorylcholine (PMPC)-poly 2-(diisopropylamino)ethyl methacrylate (PDPA) polymersomes to encapsulate chemotherapeutic agents for effective combinational anti-cancer therapy. Polymersome uptake and ability to deliver encapsulated drugs into healthy normal oral cells and oral head and neck squamous cell carcinoma (HNSCC) cells was measured in two and three-dimensional culture systems. PMPC-PDPA polymersomes were more rapidly internalised by HNSCC cells compared to normal oral cells. Polymersome cellular up-take was found to be mediated by class B scavenger receptors.We also observed that these receptors are more highly expressed by cancer cells compared to normal oral cells, enabling polymersome-mediated targeting. Doxorubicin and paclitaxel were encapsulated into pH-sensitive PMPC-PDPA polymersomes with high efficiencies either in isolation or as a dual-load for both singular and combinational delivery. In monolayer culture, only a short exposure to drug-loaded polymersomes was required to elicit a strong cytotoxic effect. When delivered to three-dimensional tumour models, PMPC-PDPA polymersomes were able to penetrate deep into the centre of the spheroid resulting in extensive cell damage when loaded with both singular and dual-loaded chemotherapeutics. PMPC-PDPA polymersomes offer a novel system for the effective delivery of chemotherapeutics for the treatment of HNSCC.Moreover, the preferential internalisation of PMPC polymersomes by exploiting elevated scavenger receptor expression on cancer cells opens up the opportunity to target polymersomes to tumours.3

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“…Thus size-dependent uptake of various NPs has been intensively investigated and widely reported. For example, for organic NPs, some researchers claimed smaller NPs resulted in higher cellular uptake [22,33], while others reported an optimal size range for highest uptake [34][35][36][37]. Ross and Hui [38] even found linearly increasing cellular uptake of lipoplex in the size range of 35-2200 nm.…”

Section: Introductionmentioning

confidence: 99%

Particle size- and number-dependent delivery to cells by layered double hydroxide nanoparticles

Dong

Parekh

2015

Journal of Colloid and Interface Science

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a b s t r a c tIt is well known that delivery efficiency to cells is highly dependent on particle size and the administered dose. However, there is a marked discrepancy in many reports, mainly due to the inconsistency in assessment of various parameters. In this particular research, we designed experiments using layered double hydroxide nanoparticles (LDH NPs) to specifically elucidate the effect of particle size, dose and dye loading manner on cellular uptake. Using the number of LDH NPs taken up by HCT-116 cells as the indicator of delivery efficiency, we found that (1) the size of sheet-like LDH in the range of 40-100 nm did not significantly affect their cellular uptake; (2) cellular uptake of 40 and 100 nm LDH NPs was increased proportionally to the number concentration below a critical value, but remained relatively constant beyond the critical value; and (3) the effect of the dye loading manner is mainly dependent on the loading capacity or yield. In particular, the loading capacity is determined by the NP specific surface area. This research may be extended to a larger size range to examine the size effect, but suggests that it is necessary to set up a protocol to evaluate the effects of NP's physicochemical properties on the cellular delivery efficiency.

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Controlling Cellular Uptake by Surface Chemistry, Size, and Surface Topology at the Nanoscale

Cited by 216 publications

References 31 publications

Chemotactic synthetic vesicles: design and applications in blood brain barrier crossing

Chemotactic synthetic vesicles: design and applications in blood brain barrier crossing

Polymersome-Mediated Delivery of Combination Anticancer Therapy to Head and Neck Cancer Cells: 2D and 3D in Vitro Evaluation

Particle size- and number-dependent delivery to cells by layered double hydroxide nanoparticles

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