c(RGDfK) decorated micellar drug delivery system for intravesical instilled chemotherapy of superficial bladder cancer

Zhou, Danhua; Zhang, Guan; Gan, Zhihua

doi:10.1016/j.jconrel.2013.01.025

Cited by 54 publications

(48 citation statements)

References 44 publications

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“…However, without uptake selection, polymeric micelles would be endocytosed by both normal cells and tumor cells during blood circulation, which leads to an unsatisfactory drug utilization and thus low therapeutic efficacy . To improve the specificity of drug delivery, targeting ligands such as folic acid and RGD peptide have been employed to functionalize the polymeric systems . These targeting ligands could actively bind to overexpressed specific receptors on tumor cell surfaces and facilitate the ligand‐receptor mediated endocytosis of polymeric micelles.…”

Section: Introductionmentioning

confidence: 99%

Grafted copolymer micelles with pH triggered charge reversibility for efficient doxorubicin delivery

Zheng

et al. 2017

J. Polym. Sci. Part A: Polym. Chem.

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The instability and premature charge reversal at pH 7.4 have become the major limitations of charge-reversal delivery systems. To address this problem, graft copolymer of poly(butylene succinate)-g-cysteamine-bi-poly(ethylene glycol) (PBS-g-CS-bi-PEG, bi 5 benzoic imine bond) was designed and synthesized through facile thiol-ene click reaction and subsequent Schiff's base reaction. Then, PBS-g-CS-bi-PEG and carboxyl-functionalized polyester of poly(butylene succinate)-g-3-mercaptopropionic acid (PBS-g-MPA) co-assemble in aqueous solution to give PEG shell-sheddable charge-reversal micelles with sizes of 85-103 nm and low polydispersity of 0.11-0.12. Interestingly, the PBS-g-MPA/CS-bi-PEG micelles could sensitively and arbitrarily switch their surface charges between negative and positive status in response to pH fluctuation via reversible protonation and deprotonation of carboxyl and amino groups, which endows the desired stability of coassembly micelles either during long-term storage or under physiological conditions. Doxorubicin (DOX) was loaded into PBS-g-MPA/CS-bi-PEG micelles with a high drug-loading content of 10.2% and entrapment efficiency of 68% as a result of electrostatic attraction. In vitro release studies revealed that less than 25% of DOX was released within 24 h in the environment mimicking the physiological condition, whereas up to 81% of DOX was released in 24 h under weak-acid condition resembling microenvironment in endosome/lysosome. In vitro cytotoxicity study suggested that blank PBS-g-MPA/CS-bi-PEG micelles possessed excellent biocompatibility, while DOXloaded PBS-g-MPA/CS-bi-PEG micelles showed significant cytotoxicity with half-maximal inhibitory concentration (IC 50 ) of 1.55-1.67 lg DOX equiv/mL. This study provides a facile and effective approach for the preparation of novel charge-reversal micelles with switchable charges and excellent biocompatibility, which are highly promising to be used as safe nanocarriers for efficient intracellular drug delivery.

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Section: Introductionmentioning

confidence: 99%

Grafted copolymer micelles with pH triggered charge reversibility for efficient doxorubicin delivery

Zheng

et al. 2017

J. Polym. Sci. Part A: Polym. Chem.

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“…Amino (NH 2 ), carboxylic (COOH), and azido (N 3 ) groups are the most useful functional groups in biomaterials . Especially, the azido group is of great interest.…”

Section: Introductionmentioning

confidence: 99%

“…[22] Amino (NH 2 ), carboxylic (COOH), and azido (N 3 ) groups are the most useful functional groups in biomaterials. [23][24][25][26][27][28][29] Especially, the azido group is of great interest. It could be converted into amino groups with reductant.…”

Section: Introductionmentioning

confidence: 99%

Hydrophilic Block Azidation of PCL‐b‐PEO Block Copolymers from Epichlorohydrin

Liu

Gan

2014

Macromolecular Bioscience

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Amphiphilic diblock copolymers poly(ϵ-caprolactone)-b-poly(ethylene oxide) (PCL-b-PEO) with well-controlled pendant azido groups along the hydrophilic PEO block, that is, poly(ϵ-caprolactone)-b-poly(ethylene oxide-co-glycidyl azide) (PCL-b-P(EO-co-GA)), are synthesized from poly(ϵ-caprolactone)-b-poly(ethylene oxide-co-epichlorohydrin) (PCL-b-P(EO-co-ECH)). The further conversion of those azido groups along the hydrophilic block of copolymers into amino or carboxyl groups via click chemistry is studied. The micelles self-assembled from PCL-b-P(EO-co-GA) with azido groups on the shell are crosslinked by the dialkynyl-PEO. The micelles with crosslinked shell show better stability, higher drug loading capacities, subsequent faster drug release rate, and higher cytotoxicity to cancer cells. The introduction of azido groups into PCL-b-PEO amphiphilic diblock copolymers from epichlorohydrin in PEO hydrophilic block in this work provides a new method for biofunctionalization of micelles via mild click chemistry.

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“…[22] In order to probe the specificity of our approach, we also investigated HEK 293T cells,w hich are reported not to interact with the RGD motif. [23] To present either unmodified or 2-functionalized DNA networks to the cells,glass slides were upgraded with walling to hold the medium, into which the cells were seeded and allowed to adhere.Loose cells were removed by washing with PBS buffer,b efore assessing the cell numbers by phasecontrast microscopy.Subsequent staining with SYBR green I confirmed the quality of the DNAn etworks on the basis of the observed green fluorescence.…”

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confidence: 99%

Designer Extracellular Matrix Based on DNA–Peptide Networks Generated by Polymerase Chain Reaction

et al. 2016

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Cell proliferation and differentiation in multicellular organisms are partially regulated by signaling from the extracellular matrix. The ability to mimic an extracellular matrix would allow particular cell types to be specifically recognized, which is central to tissue engineering. We present a new functional DNA-based material with cell-adhesion properties. It is generated by using covalently branched DNA as primers in PCR. These primers were functionalized by click chemistry with the cyclic peptide c(RGDfK), a peptide that is known to predominantly bind to αvβ3 integrins, which are found on endothelial cells and fibroblasts, for example. As a covalent coating of surfaces, this DNA-based material shows cell-repellent properties in its unfunctionalized state and gains adhesiveness towards specific target cells when functionalized with c(RGDfK). These cells remain viable and can be released under mild conditions by DNase I treatment.

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c(RGDfK) decorated micellar drug delivery system for intravesical instilled chemotherapy of superficial bladder cancer

Cited by 54 publications

References 44 publications

Grafted copolymer micelles with pH triggered charge reversibility for efficient doxorubicin delivery

Grafted copolymer micelles with pH triggered charge reversibility for efficient doxorubicin delivery

Hydrophilic Block Azidation of PCL‐b‐PEO Block Copolymers from Epichlorohydrin

Designer Extracellular Matrix Based on DNA–Peptide Networks Generated by Polymerase Chain Reaction

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