Calcium phosphate-polymeric nanoparticle system for co-delivery of microRNA-21 inhibitor and doxorubicin

Sriram, Vishnu; Lee, Joo-Youp

doi:10.1016/j.colsurfb.2021.112061

Cited by 16 publications

(7 citation statements)

References 58 publications

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“…Furthermore, the capability of these nanoparticles to deliver anti-miR21 into the cells and bring about the downregulation of miR-231 was evaluated by measuring the levels of miR21 by qPCR using Taqman chemistry. miR21 was widely reported to be significantly overexpressed in MDA-MB-231 as per various reports . These cells were then treated with an anti-miR21 plain solution and anti-miR21-loaded d CHA (25 pmol) for 6 h. Anti-miR21 plain solution depicted insignificant expression of miR21 (11.33 ± 3.05; p > 0.5) compared to anti-miR21-loaded d CHA (68 ± 1.73; p < 0.001) (Figure A).…”

Section: Resultsmentioning

confidence: 99%

“…miR21 was widely reported to be significantly overexpressed in MDA-MB-231 as per various reports. 66 These cells were then treated with an anti-miR21 to increase the levels of Bax by 1.94 ± 0.04-fold (p < 0.001) Figure 15B, of Casp3 by 2.17 ± 0.14-fold (p < 0.001) Figure 15C, and decrease the levels of Bcl2 by 0.41 ± 0.03-fold (p < 0.001) (Figure 15D). The plain anti-miR21 solution insignificantly (p > 0.05) increases the levels of Bax by 1.15 ± 0.08-fold, Casp3 by 1.25 ± 0.03-fold, and decreases the levels of Bcl2 by 0.87 ± 0.05-fold, respectively.…”

Section: H-bond Analysis Of Ha and Dcha Withmentioning

confidence: 99%

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Dendronized Polymeric Biomaterial for Loading, Stabilization, and Targeted Cytosolic Delivery of microRNA in Cancer Cells

Tambe

Patel

Shard

et al. 2022

ACS Appl. Bio Mater.

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MicroRNAs (miRNAs) are small non-coding RNAs involved in the fine-tuning of gene regulation. Anti-miRNA is a promising RNA-interference (RNAi) agent that potently regulates post-transcriptional expression of an abnormal gene by inhibiting its target mRNAs. To date, ONPATTRO and Leqvio are the only firstin-class USFDA-approved RNAi-therapeutics available in clinic. The deficiency of a fitting delivery carrier remains a primary hindrance to their clinical translation. To address this issue, this investigation reports the development of a dendronized polymeric nanobiomaterial involving a USFDA-approved biopolymer (hyaluronic acid, also called hyaluronan; HA) for the selective delivery of anti-miRNA into the cytosolic compartment of cancer cells. Dendrons are synthesized for focal cationization of HA to produce a cationic dendronized HA polymer (dCHA) using a ligated dendron motif approach. The synthesized dCHA is inert toward blood cells, as observed in the hemolysis assay. It also depicts a strong binding affinity for the CD44-receptor protein and is found to be neutral toward macrophages and albumin proteins (human origin; molecular simulation and docking tool: GROMACS). The developed approach is simple in application, offers high anti-miR21 loading, and avoids RNase enzymatic degradation of loaded anti-miRNA. The dCHA could efficiently escape the lysoendosomal compartment to mediate cytosolic delivery of the loaded anti-miRNA, ascribed to the proton sponge effect offered by weak basic groups of ligated dendron motifs in the dCHA architecture. The dCHA-loaded anti-miR21 upregulates the mRNA levels of Bax and CASP3 and downregulates the levels of Bcl2, accompanied by significant miR21 gene downregulation. Furthermore, under the influence of CD44-receptor blockade, a reduction in the cellular uptake of FAM-labeled anti-miR21 is observed compared to the control, inferring receptor-mediated uptake of dCHA. The conclusive outcome of this research advocates the use of dCHA to be a fit-to-purpose modality to load, preserve, and selectively deliver anti-miRNA-therapeutics to the cytosolic compartment of cancer cells. The developed approach has been tested using anti-miR21 as a model RNAi-therapeutic; however, the knowledge developed in this fundamental research can also be extended to other gene therapeutics, including DNA, siRNA, miRNA mimics, plasmid oligonucleotides, and so forth.

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Section: Resultsmentioning

confidence: 99%

Section: H-bond Analysis Of Ha and Dcha Withmentioning

confidence: 99%

Dendronized Polymeric Biomaterial for Loading, Stabilization, and Targeted Cytosolic Delivery of microRNA in Cancer Cells

Tambe

Patel

Shard

et al. 2022

ACS Appl. Bio Mater.

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show abstract

“… AntagomiR-21 NGO-PEG-dendrimer-antagomiR-21 MicroRNA MIR21 family miR-21 After treatment, invasive cells and migratory cancer cells decreased drastically Bioluminescence assay was carried out to check the delivery efficacy of antagomir-21 using NGO-PEG-dendrimer [ 23 ] 4. AntagomiR-21 CaP-lipid/PLLA nanoparticle MicroRNA MIR21 family miR-21 After treatment, levels of miR-21 decreased, and PTEN increased – [ 30 ] …”

Section: Rna Suppression Therapy In Lung Cancermentioning

confidence: 99%

“…A similar study led by Sriram and his group to deliver antagomir-21 using calcium phosphate coated lipid/poly l -lactic acid polymer (PLLA) based nanoparticle along with chemotherapeutic drug doxorubicin for creating the synergistic effect in killing NSCLCs [ 30 ]. Calcium phosphate coating on the nanoparticle maintains stability and enhances the chance of endosomal escape for releasing antagomir-21 and doxorubicin into the cytoplasm.…”

Section: Rna Suppression Therapy In Lung Cancermentioning

confidence: 99%