Localized controlled release of bevacizumab and doxorubicin by thermo-sensitive hydrogel for normalization of tumor vasculature and to enhance the efficacy of chemotherapy

Darge, Haile Fentahun; Andrgie, Abegaz Tizazu; Hanurry, Endiries Yibru; Birhan, Yihenew Simegniew; Mekonnen, Tefera Worku; Chou, Hsiao-Ying; Hsu, Wei‐Hsin; Lai, Juin‐Yih; Lin, Shih‐Yin; Tsai, Hsieh‐Chih

doi:10.1016/j.ijpharm.2019.118799

Cited by 43 publications

(21 citation statements)

References 65 publications

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“…The in vitro cytotoxicity of blank and DOX-loaded micelles was evaluated by MTT reduction assay [46][47][48] on HaCaT, MDCK, and HeLa cells in triplicate experiments. All cell lines were seeded into a 96-well plate at a density of 1 × 10 4 cells/well in complete DMEM and maintained in a humidified incubator at 37 • C under 5% CO 2 for 24 h. For the cell viability test, the original medium was refreshed and free DOX, DOX@NCMs, and DOX@CCMs of predetermined concentrations were added and incubated for 24 h. Next, the medium in each well was replaced with a fresh culture cell medium, and MTT reagent (5 mg/mL) was added to each well and incubated for a further 4 h. Finally, DMSO (100 µL) was added to each well and the plates were incubated at 37 • C for 25 min until all the formazan crystals were dissolved.…”

Section: In Vitro Cytotoxicity Studymentioning

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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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: In Vitro Cytotoxicity Studymentioning

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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“…The development of new supplementary or alternative tumor treatment methods based on biomaterials can avoid these side effects by selective delivery. [18][19][20][21][22][23][24][25][26] Specifically, photothermal therapy is an emerging treatment method that converts near-infrared (NIR) light into localized thermal energy to destroy tumor tissue. [27][28][29][30][31][32][33][34][35] Photothermal therapy is based on nanomaterials with strong NIR absorption, such as gold nanoparticles, [36][37][38][39][40][41] carbon nanomaterials, 42,43 magnetic nanoparticles, [44][45][46][47][48] and copper nanomaterials.…”

Section: Introductionmentioning

confidence: 99%

Review of a new bone tumor therapy strategy based on bifunctional biomaterials

et al. 2021

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Bone tumors, especially those in osteosarcoma, usually occur in adolescents. The standard clinical treatment includes chemotherapy, surgical therapy, and radiation therapy. Unfortunately, surgical resection often fails to completely remove the tumor, which is the main cause of postoperative recurrence and metastasis, resulting in a high mortality rate. Moreover, bone tumors often invade large areas of bone, which cannot repair itself, and causes a serious effect on the quality of life of patients. Thus, bone tumor therapy and bone regeneration are challenging in the clinic. Herein, this review presents the recent developments in bifunctional biomaterials to achieve a new strategy for bone tumor therapy. The selected bifunctional materials include 3D-printed scaffolds, nano/microparticle-containing scaffolds, hydrogels, and bone-targeting nanomaterials. Numerous related studies on bifunctional biomaterials combining tumor photothermal therapy with enhanced bone regeneration were reviewed. Finally, a perspective on the future development of biomaterials for tumor therapy and bone tissue engineering is discussed. This review will provide a useful reference for bone tumor-related disease and the field of complex diseases to combine tumor therapy and tissue engineering.

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“…Ideal nanocarriers are required to retain and selectively release the drug specifically in tumor cells and need to be compatible with the immune system and exhibit a long lifespan in the circulation [7,16]. A comprehensive range of nanocarriers with different nanostructures have been fabricated to enhance the therapeutic efficiency of gemcitabine, including polymersomes [17], liposomes [18], micelles [14,19], and polymeric nanoparticles, including dendrimers [15,20,21].…”

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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Localized controlled release of bevacizumab and doxorubicin by thermo-sensitive hydrogel for normalization of tumor vasculature and to enhance the efficacy of chemotherapy

Cited by 43 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

Review of a new bone tumor therapy strategy based on bifunctional biomaterials

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

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