Enhanced antitumor efficacy by cyclic RGDyK-conjugated and paclitaxel-loaded pH-responsive polymeric micelles

Gao, Yajie; Zhou, Yanxia; Zhao, Lei; Zhang, Chao; Li, Yushu; Li, Jinwen; Li, Xinru; Liu, Na

doi:10.1016/j.actbio.2015.05.021

Cited by 69 publications

(39 citation statements)

References 44 publications

(52 reference statements)

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“…Our previous work demonstrated that polymeric micelles based on diblock copolymers with poly(2-ethyl-2-oxazoline) (PEOz) hydrophilic segment exhibited pH-triggered drug release behavior, which is beneficial for enhancement of anticancer efficacy by passive targeting delivery of anticancer drugs to tumor sites and quick release of the loaded drugs in tumor cells (Gao et al., 2015a , b , c ; Wang et al., 2017 ). Furthermore, vitamin E succinate (VES) has been proved to be an effective anticancer agent with high selectivity for malignant cells without toxicity to normal cells (Duhem et al., 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Improved intestinal absorption of paclitaxel by mixed micelles self-assembled from vitamin E succinate-based amphiphilic polymers and their transcellular transport mechanism and intracellular trafficking routes

Zou

et al. 2018

Drug Delivery

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To ensure that antitumor drugs can be effectively transported across intestinal barrier and then quickly released in tumor cells, mixed polymeric micelles (Mix-PMs) were designed and fabricated by combining poly(2-ethyl-2-oxazoline)-vitamin E succinate (PEOz-VES) with TPGS1000 for enhancing intestinal absorption of paclitaxel. PEOz-VES exhibited an extremely low critical micelle concentration and negligible cytotoxicity. The Mix-PMs were characterized to have about 20 nm in diameter, uniform spherical morphology, high drug-loading content and sustained drug release profile with a retained pH-sensitivity. The results of the transport through Caco-2 cell monolayers and intestinal absorption revealed that Mix-PMs displayed higher transcellular transport efficiency compared with PEOz-VES micelles and Taxol®. The possible mechanism of transcellular transport for Mix-PMs was elucidated to be mainly through clathrin- and caveolae/lipid rafts-mediated transcytosis. Confocal laser scanning micrographs revealed that late endosomes, lysosomes, endoplasmic reticulum, Golgi apparatus, and mitochondria were all involved in intracellular trafficking of Mix-PMs. The proteins involved in transcytosis of Mix-PMs and finally excreted were unraveled for the first time by the analysis of proteins in the basolateral media according to the proteomics method. Consequently, the fabricated mixed polymeric micelles may have great potential in enhancing intestinal absorption and accelerating drug release in tumor cells.

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Section: Introductionmentioning

confidence: 99%

Improved intestinal absorption of paclitaxel by mixed micelles self-assembled from vitamin E succinate-based amphiphilic polymers and their transcellular transport mechanism and intracellular trafficking routes

Zou

et al. 2018

Drug Delivery

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“…Polymeric micelles, with a size distribution less than 100 nm, can accumulate in tumor tissue via the passive “enhanced permeability and retention (EPR) effect”. On the other hand, polymer micelle can be modified with ligand or antibody to achieve active targeting of tumor tissue 11 12 13 . Currently, several micellar formulations for anticancer therapy are under clinical evaluation, and a few of them have been FDA approved for use in patients 14 .…”

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confidence: 99%

Multifunctional SPIO/DOX-loaded A54 Homing Peptide Functionalized Dextran-g-PLGA Micelles for Tumor Therapy and MR Imaging

Situ

Wang

Zhu

et al. 2016

Sci Rep

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Specific delivery of chemotherapy drugs and magnetic resonance imaging (MRI) contrast agent into tumor cells is one of the issues to highly efficient tumor targeting therapy and magnetic resonance imaging. Here, A54 peptide-functionalized poly(lactic-co-glycolic acid)-grafted dextran (A54-Dex-PLGA) was synthesized. The synthesized A54-Dex-PLGA could self-assemble to form micelles with a low critical micelle concentration of 22.51 μg. mL−1 and diameter of about 50 nm. The synthetic A54-Dex-PLGA micelles can encapsulate doxorubicin (DOX) as a model anti-tumor drug and superparamagnetic iron oxide (SPIO) as a contrast agent for MRI. The drug-encapsulation efficiency was about 80% and the in vitro DOX release was prolonged to 72 hours. The DOX/SPIO-loaded micelles could specifically target BEL-7402 cell line. In vitro MRI results also proved the specific binding ability of A54-Dex-PLGA/DOX/SPIO micelles to hepatoma cell BEL-7402. The in vivo MR imaging experiments using a BEL-7402 orthotopic implantation model further validated the targeting effect of DOX/SPIO-loaded micelles. In vitro and in vivo anti-tumor activities results showed that A54-Dex-PLGA/DOX/SPIO micelles revealed better therapeutic effects compared with Dex-PLGA/DOX/SPIO micelles and reduced toxicity compared with commercial adriamycin injection.

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“…Peptide modification on the surface of the micelle can be used effectively for precise targeting. Integrin-binding sequence peptides with covalent bonds to the micelle can actively target tumors ( 101 ). Block copolymers are environmental response modifiers that display a physico-chemical response to stimuli such as temperature ( 102 – 104 ), pH ( 105 ), light ( 106 ), or electricity ( 107 ).…”

Section: Micellar Nanoparticlesmentioning

confidence: 99%

Cancer drug delivery in the nano era: An overview and perspectives

et al. 2017

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Nanomaterials are increasingly used as drug carriers for cancer therapy. Nanomaterials also appeal to researchers in the areas of cancer diagnosis and biomarker discovery. Several antitumor nanodrugs are currently being tested in preclinical and clinical trials and show promise in therapeutic and other settings. We review the development of nanomaterial drug carriers, including liposomes, polymer nanoparticles, dendritic polymers, and nanomicelles, for the diagnosis and treatment of various cancers. The prospects of nanomaterials as drug carriers for future clinical applications are also discussed.

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Enhanced antitumor efficacy by cyclic RGDyK-conjugated and paclitaxel-loaded pH-responsive polymeric micelles

Cited by 69 publications

References 44 publications

Improved intestinal absorption of paclitaxel by mixed micelles self-assembled from vitamin E succinate-based amphiphilic polymers and their transcellular transport mechanism and intracellular trafficking routes

Improved intestinal absorption of paclitaxel by mixed micelles self-assembled from vitamin E succinate-based amphiphilic polymers and their transcellular transport mechanism and intracellular trafficking routes

Multifunctional SPIO/DOX-loaded A54 Homing Peptide Functionalized Dextran-g-PLGA Micelles for Tumor Therapy and MR Imaging

Cancer drug delivery in the nano era: An overview and perspectives

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