Targeting tumor angiogenic vasculature using polymer–RGD conjugates

Mitra, Amitava; Mulholland, Justin; Nan, Anjan; Mcneill, Edwina; Ghandehari, Hamidreza; Line, Bruce R.

doi:10.1016/j.jconrel.2004.09.023

Cited by 141 publications

(103 citation statements)

References 32 publications

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“…As the number of peptide copies, in applications exploiting polyvalent interactions of peptide sequences, vary according to the different candidate sequences, no general length of the polymer backbone can be predetermined. The length of the polymers obtained here, allowing the conjugation of up to 20 peptide copies on average was deemed suitable for the application targeted [17]. They were purified by Size-Exclusion Chromatography (SEC) using Sephadex LH20 to remove byproducts and analysed by 1 H-NMR, MALDI-TOF MS and analytical RP-HPLC where possible.…”

Section: Resultsmentioning

confidence: 99%

Poly(Ethylene Glycol)-Based Backbones with High Peptide Loading Capacities

et al. 2014

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Polymer-peptide conjugates are a promising class of compounds, where polymers can be used to overcome some of the limitations associated with peptides intended for therapeutic and/or diagnostic applications. Linear polymers such as poly(ethylene glycol) can be conjugated through terminal moieties and have therefore limited loading capacities. In this research, functionalised linear poly(ethylene glycol)s are utilised for peptide conjugation, to increase their potential loading capacities. These poly(ethylene glycol) derivatives are conjugated to peptide sequences containing representative side-chain functionalised amino acids, using different conjugation chemistries, including copper-catalysed azide-alkyne cycloaddition, amide coupling and thiol-ene reactions. Conjugation of a sequence containing the RGD motif to poly(allyl glycidyl ether) by the thiol-ene reaction, provided a conjugate which could be used in platelet adhesion studies.

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Section: Resultsmentioning

confidence: 99%

Poly(Ethylene Glycol)-Based Backbones with High Peptide Loading Capacities

et al. 2014

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“…For example HPMA copolymers containing cyclic Arg-GlyAsp peptides have been developed for targeting αvβ3 integrins expressed on angiogenic tumor blood vessels and other tumor cells. The anticancer and antiangiogenic agent, geldanamycin (aminohexylgeldanamycin), was conjugated to the polymer backbone through a lysosome-degradable GFLG (Gly-Phe-Leu-Gly) linker and the molecular weight was maintained at 40 kDa to ensure renal clearance after administration (112)(113)(114)(115)(116). The authors reported significantly higher localization of drug-loaded HPMA copolymer containing the arginylglycylaspartic acid (RGD) peptide (target moiety) in tumour cells and tumour growth suppression in prostate cancer bearing mice compared to control without a targeting moiety.…”

Section: Active Targetingmentioning

confidence: 99%

Polymer-Drug Nanoconjugate – An Innovative Nanomedicine: Challenges and Recent Advancements in Rational Formulation Design for Effective Delivery of Poorly Soluble Drugs

Abioye

Chi-Tangyie²,

Kola-Mustapha³

et al. 2016

PNT

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Background: Over the last four decades, the use of water soluble polymers in rational formulation design has rapidly evolved into valuable drug delivery strategies to enhance the safety and therapeutic effectiveness of poorly soluble drugs, particularly anticancer drugs. Novel advances in polymer chemistry have provided new generations of well defined polymeric architectures for specific applications in polymer-drug conjugate design. However, total control of crucial parameters such as particle size, molecular weight distribution, polydispersity, localization of charges, hydrophilic-lipophilic balance and non site-specific coupling reactions during conjugation has been a serious challenge. Objective: This review briefly describes the current advances in polymer-drug nanoconjugate design and various challenges hindering their transformation into clinically useful medicines. Method: Existing literature was reviewed. Results: This review provides insights into the significant impact of covalent and non-covalent interactions between drug and polymer on drug loading (or conjugation) efficiency, conjugate stability, mechanism of drug release from the conjugate and biopharmaceutical properties of poorly soluble drugs. The utility values and application of Quality by Design principles in rational design, optimization and control of the Critical Quality Attributes (CQA) and Critical Process Parameters (CPP) that underpin the safety, quality and efficacy of the nanoconjugates are also presented. Conclusion: It was apparent that better understanding of the physicochemical properties of the nanoconjugates as well as the drug-polymer interaction during conjugation process is essential to be able to control the biodistribution, pharmacokinetics, therapeutic activity and toxicity of the nanoconjugates which will in turn enhance the prospect of successful transformation of these promising nanoconjugates into clinically useful nanomedicines.

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“…The crosslinkers are degradable at pH < 6, which allows release of the virion from the polymer shell at an acidic environment such as endosomes. To target Hela cells, cyclic arginine-glycine-aspartic acid (cRGD), which displays a strong affinity and selectivity to the a V b 3 integrin and is abundantly expressed on tumor endothelial and tumor cells (Mitra et al, 2005), was polymerized to the polymer shell in the form of acrylamidetailored cRGD to generate targeting nanovirus.…”

Section: Synthesis Of Targeting Nanovirusmentioning

confidence: 99%

Retargeting Vesicular Stomatitis Virus Glycoprotein Pseudotyped Lentiviral Vectors with Enhanced Stability byIn SituSynthesized Polymer Shell

Liang

Yan

et al. 2013

Human Gene Therapy Methods

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The ability to introduce transgenes with precise specificity to the desired target cells or tissues is key to a more facile application of genetic therapy. Here, we describe a novel method using nanotechnology to generate lentiviral vectors with altered recognition of host cell receptor specificity. Briefly, the infectivity of the vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped lentiviral vectors was shielded by a thin polymer shell synthesized in situ onto the viral envelope, and new binding ability was conferred to the shielded virus by introducing acrylamide-tailored cyclic arginine-glycine-aspartic acid (cRGD) peptide to the polymer shell. We termed the resulting virus ''targeting nanovirus.'' The targeting nanovirus had similar titer with VSV-G pseudotypes and specifically transduced Hela cells with high transduction efficiency. In addition, the encapsulation of the VSV-G pseudotyped lentivirus by the polymer shell did not change the pathway that VSV-G pseudotypes enter and fuse with cells, as well as later events such as reverse transcription and gene expression. Furthermore, the targeting nanovirus possessed enhanced stability in the presence of human serum, indicating protection of the virus by the polymer shell from human serum complement inactivation. This novel use of nanotechnology demonstrates proof of concept for an approach that could be more generally applied for redirecting viral vectors for laboratory and clinical purposes.

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Targeting tumor angiogenic vasculature using polymer–RGD conjugates

Cited by 141 publications

References 32 publications

Poly(Ethylene Glycol)-Based Backbones with High Peptide Loading Capacities

Poly(Ethylene Glycol)-Based Backbones with High Peptide Loading Capacities

Polymer-Drug Nanoconjugate – An Innovative Nanomedicine: Challenges and Recent Advancements in Rational Formulation Design for Effective Delivery of Poorly Soluble Drugs

Retargeting Vesicular Stomatitis Virus Glycoprotein Pseudotyped Lentiviral Vectors with Enhanced Stability byIn SituSynthesized Polymer Shell

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