In vitro siRNA delivery via diethylenetriamine- and tetraethylenepentamine-modified carboxyl group-terminated Poly(amido)amine generation 4.5 dendrimers

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

doi:10.1016/j.msec.2019.110245

Cited by 14 publications

(16 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These cytotoxicity studies confirmed that both the G4.5 PAMAM dendrimer and the hydrogel showed negligible toxicity towards different cells lines even at their highest doses. Thus, the biocompatibility studies of both the Na-DOC-hydrogel and G4.5 PAMAM dendrimer confirmed that the current drug delivery system conforms with the background information from the literature [ 27 , 28 ] and the results of former studies [ 37 , 38 , 40 ] and that it can be used safely in animal models as anticancer co-drug delivery system for DOX and RESV.…”

Section: Resultssupporting

confidence: 79%

“…The release pattern of DOX from G4.5-DOX and that of RESV and DOX from Na-DOC-hyd-RESV+G4.5-DOX were tested in media of different pH (5.0, 6.5 and 7.4). DOX release studies from G4.5-DOX were performed based on a previously reported method [ 35 , 36 , 37 , 38 , 40 ]. Briefly, 1.0 mL G4.5-DOX solution was placed in a dialysis tube (membrane with 1 kDa MW cut-offs) and immersed in a separate vial containing 10 mL PBS at various pH (5.0, 6.5 and 7.4).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Bioinspired Composite, pH-Responsive Sodium Deoxycholate Hydrogel and Generation 4.5 Poly(amidoamine) Dendrimer Improves Cancer Treatment Efficacy via Doxorubicin and Resveratrol Co-Delivery

et al. 2020

Self Cite

View full text Add to dashboard Cite

Maximizing the antitumor efficacy of doxorubicin (DOX) with a new drug delivery strategy is always desired in the field of biomedical science. Because the clinical applications of DOX in the treatment of cancer is limited by the side effects related to the dose. Herein, we report the co-loading of DOX and resveratrol (RESV) using an injectable in situ formed sodium deoxycholate hydrogel (Na-DOC-hyd) at the pH of the tumor extracellular microenvironment. The sequential, controlled, and sustained release of RESV and DOX for synergistic antitumor effects was confirmed by entrapping G4.5-DOX in the RESV-loaded Na-DOC hydrogel (Na-DOC-hyd-RESV). The synergistic antitumor activity of Na-DOC-hyd-RESV+G4.5-DOX was assessed on HeLa cell xenograft tumor in BALB/c nude mice. In the MTT biocompatibility assay, both the G4.5 PAMAM dendrimer and Na-DOC-hyd exhibited negligible cytotoxicity up to the highest dose of 2.0 mg mL−1 in HeLa, MDA-MB-231, and HaCaT cells. The release profiles of DOX and RESV from the Na-DOC-hyd-RESV+G4.5-DOX confirmed the relatively rapid release of RESV (70.43 ± 1.39%), followed by that of DOX (54.58 ± 0.62%) at pH 6.5 in the 7 days of drug release studies. A single intratumoral injection of Na-DOC-hyd-RESV+G4.5-DOX maximally suppressed tumor growth during the 28 days of the treatment period. Na-DOC-hyd-RESV+G4.5-DOX did not cause any histological damage in the major visceral organs. Therefore, this Na-DOC-hydrogel for dual drugs (DOX and RESV) delivery at the pH of the tumor extracellular microenvironment is a promising, safe, and effective combination for antitumor chemotherapy.

show abstract

Section: Resultssupporting

confidence: 79%

Section: Methodsmentioning

confidence: 99%

Bioinspired Composite, pH-Responsive Sodium Deoxycholate Hydrogel and Generation 4.5 Poly(amidoamine) Dendrimer Improves Cancer Treatment Efficacy via Doxorubicin and Resveratrol Co-Delivery

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Dendrimers are the three-dimensional, hyper-branched macromolecules containing core, void space, and reactive surface regions [22,23]. The poly(amido)amine (PAMAM) dendrimer has been extensively explored as a gene and drug carrier system [24,25]; its advantages of simple fabrication, nanometer size, non-immunogenicity, water solubility, biodegradability, and biocompatibility make the PAMAM dendrimer a suitable synthetic polymer for drug delivery systems [26]. The uniformity and hyper-branched characteristics of PAMAM enable the dendrimer to cross the cell membrane of cancer cells and carry a high cargo content [27].…”

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…As the concentration of Chl increased, more Chl molecules were distributed in the prodrug bilayer, resulting in an increase in the particle size [34]. The size of each prodrug nanoparticle determined from AFM data was smaller than that from the DLS data [21,35]. As samples for AFM measurement were dried on silica waiver, the nanoparticles were estimated to be smaller; whereas, for DLS measurement, the diameter of the hydrated layer is considered and therefore the nanoparticles were bigger.…”

Section: Formation Of the Self-assembled Prodrugmentioning

confidence: 99%

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

et al. 2019

Self Cite

View full text Add to dashboard Cite

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.

show abstract

In vitro siRNA delivery via diethylenetriamine- and tetraethylenepentamine-modified carboxyl group-terminated Poly(amido)amine generation 4.5 dendrimers

Cited by 14 publications

References 54 publications

Bioinspired Composite, pH-Responsive Sodium Deoxycholate Hydrogel and Generation 4.5 Poly(amidoamine) Dendrimer Improves Cancer Treatment Efficacy via Doxorubicin and Resveratrol Co-Delivery

Bioinspired Composite, pH-Responsive Sodium Deoxycholate Hydrogel and Generation 4.5 Poly(amidoamine) Dendrimer Improves Cancer Treatment Efficacy via Doxorubicin and Resveratrol Co-Delivery

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

Contact Info

Product

Resources

About