Targeting of Cancer Cells Using Click-Functionalized Polymer Capsules

Kamphuis, Marloes M. J.; Johnston, Angus P. R.; Such, Georgina K.; Dam, Henk H.; Evans, Richard A.; Scott, Andrew M.; Nice, Edouard C.; Heath, Joan K.; Caruso, Frank

doi:10.1021/ja106405c

Cited by 162 publications

(164 citation statements)

References 9 publications

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“…We have also demonstrated the ability to encapsulate paclitaxel and doxorubicin in combination into polymersomes and have shown that polymersome mediated drug delivery increases the cytotoxicity compared to free drugs. The potential of superficially targeting tumour cells by conjugating tumour-specific ligands to the surface of polymersomes 48 may further decrease offtarget cytotoxicity and reduce the levels of drugs needed to achieve systemic coverage. Table 1.…”

Section: Cellular Internalisation Kineticsmentioning

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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Section: Cellular Internalisation Kineticsmentioning

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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“…Such capsules sensitive to external conditions e.g., magnetic field should contain magnetic particles [281] or they have special receptor molecules like antibodies (Ab) attached to the outer side of the shell [282]. The Ab can be adsorb by electrostatic interactions [283] or covalently liked to surfaces [284][285][286][287][288]. For uncharged materials like poly(ethylene glycol) (PEG) or poly(N-vinylpyrrolidone) (PVPON) covalent attachment of the Ab is required since electrostatic attachment is not effective for lowfouling materials because they inhibit nonspecific protein binding.…”

Section: Stimulus Responsive Shell-tuning Capsules For Drug Deliverymentioning

confidence: 99%

“…The pre-condensation of pDNA with peptides improves lipid-based delivery systems and transfection efficiencies [326]. At last, by using LbL method Caruso et al [284][285][286][287][288] synthesized redoxactive polymeric microcapsules with the cross-linked shell containing disulfide bonds for the delivery of a siRNA targeting to PC-3 prostate cancer cells. The polycation-polylysine (PLL) for a siRNA complexation was infiltrated into the pores of nanoporous silica particles prior to an assembly of layer from the negatively charged poly(methacrylic acid) with thiol-modified groups (PMASH).…”

Section: Polymer Micelles and Capsules Loaded With Fluorescent Therapmentioning

confidence: 99%

Fluorescent Dyes Used in Polymer Carriers as Imaging Agents in Anticancer Therapy

Miksa¹

2016

Med chem (Los Angeles)

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This review highlights the role of fluorescent dyes as active "molecular photoswiches" focusing on the application in bioimaging and anticancer therapies in the field of therapeutic delivery. The author describes the development of prodrugs targeted to specific cell types and polymeric nanocarriers (capsules, micelles and silica nanoparticles) used as fluorescent probes which offer advantages in the integration of "smart" features of fluorescent dyes into synthetic materials. The incorporation of biologically responsive components that cleave upon changes in pH or light irradiation is fundamental to the successful design of such carriers with capabilities to load and release therapeutics specifically at a target site.

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“…88 This unique feature is often referred to as a "stealth" effect, since opsonisation by macrophages and non-specific binding to cells is dramatically decreased. 89 Moreover, due to their soft architecture, microgels are able to flatten themselves onto vascular surfaces, thus simultaneously anchoring in multiple points. Thereby, their retention in the targeted disease site is enhanced.…”

Section: Microgels For Loading and Release Applicationsmentioning

confidence: 99%

Light-Sensitive Polymeric Nanoparticles Based on Photo-Cleavable Chromophores

Klinger

2013

Springer Theses

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This thesis focuses on the design, synthesis and characterization of novel photo-sensitive microgels and nanoparticles as potential materials for the loading and light-triggered release/accessibility of functional compounds. In order to realize this concept, different approaches to irradiation-dependent response mechanisms have been investigated.Novel light-cleavable divinyl functionalized monomeric crosslinkers based on o-nitrobenzyl derivatives were synthesized and used for the preparation of either PMMA or hydroxyl functionalized PHEMA microgels swellable and degradable in organic solvents. By the introduction of anionic MAA moieties into the PHEMA microgels, this concept was successfully transferred to double stimuli-responsive p(HEMA-co-MAA) hydrogel nanoparticles exhibiting a pH-dependent swelling and light-induced degradation behavior in aqueous media. This sensitivity to two orthogonal triggers is proposed to combine a pHinduced post-formation loading mechanism with a pH-and light-triggered release. In addition, a new class of enzyme-and light-sensitive PAAm microgels based on (meth-)acrylate functionalized dextrans as photo-and enzymatically degradable macromolecular crosslinkers was developed by introducing a photo-labile linker between the enzymatically degradable dextran chain and the polymerizable vinyl moieties. Here, the water solubility of the crosslinkers is assumed to enable an in situ loading approach of hydrophilic compounds.A different approach to the loading of microgels is based on photo-labile covalent microgel-drug conjugates. The first step to the realization of this concept was achieved by the development of a novel functional monomer consisting of a doxorubicin molecule covalently attached to a radically polymerizable methacrylate group via a photo-cleavable linker.Moreover, in order to enable the release of hydrophobic substances in aqueous media, hydrophobic nanoparticles consisting of a photo-resist polymer were designed to be degradable upon irradiation in water. Light-triggered conversion of the initial hydrophobic polymer into hydrophilic PMAA induced in situ particle dissolution and release of nile red.Since the introduction of a stimuli-responsive shell around a microgel is assumed to prevent leakage of embedded compounds, studies on non-stimuli-responsive shell formation around preformed microgel seed particles and the formation of microgel cores in polymeric shells were conducted to investigate potential synthetic pathways to this approach.In a last attempt, the surface of PHEMA and p(HEMA-co-MAA) microgels was functionalized with cinnamoyl groups in order to trigger the (reversible) particles interaction with each other by light-induced [2+2] cycloaddition reactions.

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Targeting of Cancer Cells Using Click-Functionalized Polymer Capsules

Cited by 162 publications

References 9 publications

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

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

Fluorescent Dyes Used in Polymer Carriers as Imaging Agents in Anticancer Therapy

Light-Sensitive Polymeric Nanoparticles Based on Photo-Cleavable Chromophores

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