Fabrication of redox-responsive Bi(mPEG-PLGA)-Se2 micelles for doxorubicin delivery

Birhan, Yihenew Simegniew; Hailemeskel, Balkew Zewge; Mekonnen, Tefera Worku; Hanurry, Endiries Yibru; Darge, Haile Fentahun; Andrgie, Abegaz Tizazu; Chou, Hsiao-Ying; Lai, Juin‐Yih; Hsiue, Ging‐Ho; Tsai, Hsieh‐Chih

doi:10.1016/j.ijpharm.2019.118486

Cited by 35 publications

(30 citation statements)

References 65 publications

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“…For cellular uptake experiments, fully grown HeLa and HaCaT were trypsinized and seeded into 35 mm glass-bottom culture dishes (MatTek Corporation) at a density of 2 × 10 5 cells/well in complete DMEM and maintained in a humidified incubator at 37 • C under 5% CO 2 for 24 h. Then, 3 µg/mL of free DOX, DOX@NCMs, and DOX@CCMs (at equivalent DOX concentrations) were added to different treatment groups. After 3 and 9 h, cells were rinsed with PBS, stained with DAPI (300 nm) for 15 min, fixed with 4% paraformaldehyde solution, and the cellular uptake and localization of free DOX, DOX@NCMs, and DOX@CCMs were observed using a fluorescent microscope [3].…”

Section: Cellular Uptake Studymentioning

confidence: 99%

“…For instance, PMs with optimum micellar size (mostly less than 200 nm) tend to accumulate in cancer tissues through the EPR effect [53]. On the contrary, too small (less than 5 nm) or too large (submicron level) PMs suffered from rapid clearance from the body via renal excretion and the MNP system, respectively, upon intravenous administration [3,54]. In our study, we synthesized the mPEG-P(LA-DSeDEA)-PCL copolymer which self-assembled into micellar aggregates due to the presence of chemically distinct blocks, hydrophilic mPEG, and hydrophobic P(LA-DSeDEA)-PCL [3].…”

Section: Self-assembly and Preparation Of Core Crosslinked Polymeric mentioning

confidence: 99%

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Fabrication of Core Crosslinked Polymeric Micelles as Nanocarriers for Doxorubicin Delivery: Self-Assembly, In Situ Diselenide Metathesis and Redox-Responsive Drug Release

et al. 2020

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Polymeric micelles (PMs) have been used to improve the poor aqueous solubility, slow absorption and non-selective biodistribution of chemotherapeutic agents (CAs), albeit, they suffer from disassembly and premature release of payloads in the bloodstream. To alleviate the thermodynamic instability of PMs, different core crosslinking approaches were employed. Herein, we synthesized the poly(ethylene oxide)-b-poly((2-aminoethyl)diselanyl)ethyl l-aspartamide)-b-polycaprolactone (mPEG-P(LA-DSeDEA)-PCL) copolymer which self-assembled into monodispersed nanoscale, 156.57 ± 4.42 nm, core crosslinked micelles (CCMs) through visible light-induced diselenide metathesis reaction between the pendant selenocystamine moieties. The CCMs demonstrated desirable doxorubicin (DOX)-loading content (7.31%) and encapsulation efficiency (42.73%). Both blank and DOX-loaded CCMs (DOX@CCMs) established appreciable colloidal stability in the presence of bovine serum albumin (BSA). The DOX@CCMs showed redox-responsive drug releasing behavior when treated with 5 and 10 mM reduced glutathione (GSH) and 0.1% H2O2. Unlike the DOX-loaded non-crosslinked micelles (DOX@NCMs) which exhibited initial burst release, DOX@CCMs demonstrated a sustained release profile in vitro where 71.7% of the encapsulated DOX was released within 72 h. In addition, the in vitro fluorescent microscope images and flow cytometry analysis confirmed the efficient cellular internalization of DOX@CCMs. The in vitro cytotoxicity test on HaCaT, MDCK, and HeLa cell lines reiterated the cytocompatibility (≥82% cell viability) of the mPEG-P(LA-DSeDEA)-PCL copolymer and DOX@CCMs selectively inhibit the viabilities of 48.85% of HeLa cells as compared to 15.75% of HaCaT and 7.85% of MDCK cells at a maximum dose of 10 µg/mL. Overall, all these appealing attributes make CCMs desirable as nanocarriers for the delivery and controlled release of DOX in tumor cells.

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Section: Cellular Uptake Studymentioning

confidence: 99%

Section: Self-assembly and Preparation Of Core Crosslinked Polymeric mentioning

confidence: 99%

Fabrication of Core Crosslinked Polymeric Micelles as Nanocarriers for Doxorubicin Delivery: Self-Assembly, In Situ Diselenide Metathesis and Redox-Responsive Drug Release

et al. 2020

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“…In the present study, we designed a strategy to couple biotin with a diethylenetriamine (DETA)-modified PG4.5 dendrimer using click chemistry (Scheme 1). DETA act as a cross-linker to conjugate biotin with the half-generation PAMAM dendrimer (PG4.5) and enable optimum, controlled drug release via proton sponge effect [45,46]. Following the synthesis, the physicochemical and biological properties of gemcitabine loaded PG4.5-DETA-biotin nanoparticles were characterized to examine the therapeutic efficiency of gemcitabine in HeLa cells (Scheme 2).…”

Section: Introductionmentioning

confidence: 99%

Biotin-Decorated PAMAM G4.5 Dendrimer Nanoparticles to Enhance the Delivery, Anti-Proliferative, and Apoptotic Effects of Chemotherapeutic Drug in Cancer Cells

et al. 2020

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Biotin receptors are overexpressed by various types of solid cancer cells and play a significant role in tumor metabolism, growth, and metastasis. Thus, targeting the biotin receptors on tumor cells may enhance the efficiency and reduce the side-effects of chemotherapy. The aim of this study was to develop a biotin-coupled poly(amido)amine (PAMAM) (PG4.5) dendrimer nanoparticle to enhance the tumor-specific delivery and intracellular uptake of anticancer drugs via receptor-mediated endocytosis. We modified PG4.5 with diethylenetriamine (DETA) followed by biotin via an amide bond and characterized the resulting PG4.5-DETA-biotin nanoparticles by 1H NMR, FTIR, and Raman spectroscopy. Loading and releasing of gemcitabine (GEM) from PG4.5-DETA-biotin were evaluated by UV–Visible spectrophotometry. Cell viability and cellular uptake were examined by MTT assay and flow cytometry to assess the biocompatibility, cellular internalization efficiency and antiproliferative activity of PG4.5-DETA-biotin/GEM. Gemcitabine-loaded PG4.5-DETA-biotin nanoparticles were spherical with a particle size of 81.6 ± 6.08 nm and zeta potential of 0.47 ± 1.25 mV. Maximum drug-loading content and encapsulation efficiency were 10.84 ± 0.16% and 47.01 ± 0.71%, respectively. Nearly 60.54 ± 1.99% and 73.96 ± 1.14% of gemcitabine was released from PG4.5-DETA-biotin/GEM nanoparticles after 48 h at the acidic pH values of 6.5 and 5, respectively. Flow cytometry and fluorescence microscopy of cellular uptake results revealed PG4.5-DETA-biotin/GEM nanoparticles selectively targeted cancer cells in vitro. Cytotoxicity assays demonstrated gemcitabine-loaded PG4.5-DETA-biotin significantly reduced cell viability and induced apoptosis in HeLa cells. Thus, biotin-coupled PG4.5-DETA nanocarrier could provide an effective, targeted drug delivery system and selectively convey gemcitabine into tumor cells.

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“…Moreover, free Hep could help reduce cancer cell metastasis as reported in our previous study [12]. Therefore, the Hep-Chl prodrug nanoparticles selectively killed more tumor cells than the normal cells because of the high redox potential gradient between the tumor and normal cells [20,21].…”

Section: In Vitro Cytotoxicity Studymentioning

confidence: 67%

“…Introducing a stimuli-sensitive linker between two bioactive molecules is an additional advantageous approach to upgrade the prodrug delivery system, which allows rapid drug release due to being triggered by specified stimuli [20,21]. A stimuli-responsive system is an extensively studied method to trigger the release of active drugs from prodrugs [22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Redox-Responsive Heparin–Chlorambucil Conjugate Polymeric Prodrug for Improved Anti-Tumor Activity

et al. 2019

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Polymeric prodrug-based delivery systems have been extensively studied to find a better solution for the limitations of a single drug and to improve the therapeutic and pharmacodynamics properties of chemotherapeutic agents, which can lead to efficient therapy. In this study, redox-responsive disulfide bond-containing amphiphilic heparin–chlorambucil conjugated polymeric prodrugs were designed and synthesized to enhance anti-tumor activities of chlorambucil. The conjugated prodrug could be self-assembled to form spherical vesicles with 61.33% chlorambucil grafting efficiency. The cell viability test results showed that the prodrug was biocompatible with normal cells (HaCaT) and that it selectively killed tumor cells (HeLa cells). The uptake of prodrugs by HeLa cells increased with time. Therefore, the designed prodrugs can be a better alternative as delivery vehicles for the chlorambucil controlled release in cancer cells.

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Fabrication of redox-responsive Bi(mPEG-PLGA)-Se2 micelles for doxorubicin delivery

Cited by 35 publications

References 65 publications

Fabrication of Core Crosslinked Polymeric Micelles as Nanocarriers for Doxorubicin Delivery: Self-Assembly, In Situ Diselenide Metathesis and Redox-Responsive Drug Release

Fabrication of Core Crosslinked Polymeric Micelles as Nanocarriers for Doxorubicin Delivery: Self-Assembly, In Situ Diselenide Metathesis and Redox-Responsive Drug Release

Biotin-Decorated PAMAM G4.5 Dendrimer Nanoparticles to Enhance the Delivery, Anti-Proliferative, and Apoptotic Effects of Chemotherapeutic Drug in Cancer Cells

Redox-Responsive Heparin–Chlorambucil Conjugate Polymeric Prodrug for Improved Anti-Tumor Activity

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