Combination cytotoxicity of backbone degradable HPMA copolymer gemcitabine and platinum conjugates toward human ovarian carcinoma cells

Duangjai, Acharaporn; Luo, Kui; Zhou, Yan; Yang, Jiyuan; Kopeček, Jindřich

doi:10.1016/j.ejpb.2013.11.008

Cited by 52 publications

(35 citation statements)

References 43 publications

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“…The polymeric micelles were based on p(HPMAm), which were shown to be safe and biocompatible. [37][38][39][40][41] Dy-488 and Dy-676 were conjugated to the micellar core, which mimics drug loading in micelles. Moreover, the important surface properties of the micelles, e.g., PEG chain flexibility, hydrophilicity and charge, are not changed by this strategy.…”

Section: Introductionmentioning

confidence: 99%

Fluorophore Labeling of Core-Crosslinked Polymeric Micelles for Multimodal In Vivo and Ex Vivo Optical Imaging

Shi

Kunjachan

et al. 2015

Nanomedicine (Lond.)

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Aim-To enable multimodal in vivo and ex vivo optical imaging of the biodistribution and tumor accumulation of core-crosslinked polymeric micelles (CCPM).Materials & Methods-mPEG-b-p(HPMAm-Lac)-based polymeric micelles, core-crosslinked via cystamine and covalently labeled with two fluorophores (Dy-676/488) were synthesized. The CCPM were intravenously injected in CT26 tumor-bearing mice.Results-Upon intravenous injection, the CCPM accumulated in CT26 tumors reasonably efficiently, with values reaching ~4 %ID at 24 hours. Ex vivo TPLSM confirmed efficient extravasation of the iCCPM out of tumor blood vessels and deep penetration into the tumor interstitium.Conclusions-CCPM were labeled with multiple fluorophores, and they exemplify that combining different in vivo and ex vivo optical imaging techniques is highly useful for analyzing the biodistribution and tumor accumulation of nanomedicines.

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Section: Introductionmentioning

confidence: 99%

Fluorophore Labeling of Core-Crosslinked Polymeric Micelles for Multimodal In Vivo and Ex Vivo Optical Imaging

Shi

Kunjachan

et al. 2015

Nanomedicine (Lond.)

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“…The results demonstrated synergistic effects of HPMA copolymer-drug (SOS thiophene, DOX, and chlorin e 6 ) conjugate combinations in a wide range of concentrations. Recently, the regions of synergism for the combination of backbone degradable HPMA copolymer-gemcitabine and HPMA copolymer-paclitaxel conjugates [170] and backbone degradable HPMA copolymer-gemcitabine and HPMA copolymer-platinum conjugates [171] have been identified.…”

Section: Water-soluble Polymer-drug Conjugatesmentioning

confidence: 99%

Macromolecular therapeutics

Yang

Kopeček

2014

Journal of Controlled Release

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This review covers water-soluble polymer-drug conjugates and macromolecules that possess biological activity without attached low molecular weight drugs. The main design principles of traditional and backbone degradable polymer-drug conjugates as well as the development of a new paradigm in nanomedicines – (low molecular weight) drug-free macromolecular therapeutics are discussed. To address the biological features of cancer, macromolecular therapeutics directed to stem/progenitor cells and the tumor microenvironment are deliberated. Finally, the future perspectives of the field are briefly debated.

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“…The results demonstrated synergistic effects of HPMA copolymer-drug (SOS thiophene, DOX, and chlorin e 6 ) conjugate combinations in a wide range of concentrations. Recently, the regions of synergism for the combination of backbone degradable HPMA copolymer-gemcitabine and HPMA copolymer-paclitaxel conjugates [85] and backbone degradable HPMA copolymer-gemcitabine and HPMA copolymer-platinum conjugates [86] have been identified.…”

Section: Traditional Hydrogels and Water-soluble Polymeric Drug Camentioning

confidence: 99%

Polymeric biomaterials and nanomedicines

Yang

Kopeček

2015

Journal of Drug Delivery Science and Technology

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This overview intends to demonstrate the close relationship between the design of smart biomaterials and water-soluble polymer-drug conjugates. First, the discovery and systematic studies of hydrogels based on crosslinked poly(meth)acrylic acid esters and substituted amides is described. Then, the lessons learned for the design of water-soluble polymers as drug carriers are highlighted. The current state-of-the-art in water-soluble, mainly poly[N-(2-hydroxypropyl)methacylamide (HPMA), polymer-drug conjugates is shown including the design of backbone degradable HPMA copolymer carriers. In the second part, the modern design of hybrid hydrogels focuses on the self-assembly of hybrid copolymers composed from the synthetic part (backbone) and biorecognizable grafts (coiled-coil forming peptides or morpholino oligonucleotides) is shown. The research of self-assembling hydrogels inspired the invention and design of drug-free macromolecular therapeutics – a new paradigm in drug delivery where crosslinking of non-internalizating CD20 receptors results in apoptosis in vitro and in vivo. The latter is mediated by biorecognition of complementary motifs; no low molecular weight drug is needed.

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Combination cytotoxicity of backbone degradable HPMA copolymer gemcitabine and platinum conjugates toward human ovarian carcinoma cells

Cited by 52 publications

References 43 publications

Fluorophore Labeling of Core-Crosslinked Polymeric Micelles for Multimodal In Vivo and Ex Vivo Optical Imaging

Fluorophore Labeling of Core-Crosslinked Polymeric Micelles for Multimodal In Vivo and Ex Vivo Optical Imaging

Macromolecular therapeutics

Polymeric biomaterials and nanomedicines

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