Preparation of Microspheres Encapsulating a Recombinant TIMP-1 Adenovirus and their Inhibition of Proliferation of Hepatocellular Carcinoma Cells

Dong, Xia; Yao, Hui; Liu, Qing; Xu, Liang

doi:10.7314/apjcp.2012.13.12.6363

Cited by 3 publications

(7 citation statements)

References 21 publications

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“…Previously, acute toxicological experiments of blank microspheres showed that the microsphere vectors themselves were nontoxic with no side effects in accordance with the requirements of in vivo applications (6). In the present study, the HCC cell line HepG2 was transfected with rAd-microspheres, which displayed the highest transfection efficiency (~90%) compared with other microspheres.…”

Section: Discussionsupporting

confidence: 73%

“…3). A toxicity test of blank microspheres demonstrated that the microspheres were nontoxic with few side effects in accordance with the requirements for microspheres for in vivo application (6).…”

Section: Resultssupporting

confidence: 67%

“…The use of recombinant adenoviral vectors as an alternative delivery method for genes or combinations of genes to tumor cells is being investigated (6,(15)(16)(17). Since adenoviruses are able to efficiently enter replicating and quiescent cells, it may be used as a prospective mediator for macromolecular transport into cells.…”

Section: Discussionmentioning

confidence: 99%

“…PELA (Chengdu Institution of Organic Chemistry, Chinese Academy of Science, Chengdu, China) were used to prepare the polymer microsphere. The target microspheres were prepared by solvent extraction based on the formation of a modified double-emulsion water-1/oil/water-2 (W 1 /O/W 2 ) system as reported previously (6). Briefly, inner aqueous phase (W 1 ) was prepared with adenovirus aqueous solution, Oil phase (O) was prepared with 20% PELA solution (200 g/l) dissolved in methylene chloride, and external aqueous phase (W 2 ) was prepared with 2.0% polyvinyl alcohol aqueous solution (20 g/l).…”

Section: Experimental Animals Cell Lines and Culture Methodmentioning

confidence: 99%

“…The virus titer in the remaining liquid following encapsulation was determined and compared with the antecedent titer. The encapsulation efficiency and virus loading rate were calculated as previously described (6). To measure the viral release from rAd-microsphere preparations, the virus titers at 0, 24,48,72,96,120,144,168,192,216 and 240 h were determined by assessing their fluorescence, and virus release curves were plotted.…”

Section: Experimental Animals Cell Lines and Culture Methodmentioning

confidence: 99%

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Microencapsulation of recombinant adenovirus within poly-DL-lactide-poly(ethylene glycol) microspheres for enhanced gene transfection efficiency and inhibitory effects on hepatocellular carcinoma cells in vitro

Dong

Feng

et al. 2015

Molecular Medicine Reports

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When gene therapy is performed for the treatment of malignant tumors, gene transfer efficiency and selectivity are highly important. Polymer vehicle microspheres are a novel type of therapy, which have been developed rapidly in recent years and are able to control drug release, prolong the biological half-life of drugs, decrease side effects and achieve targeted delivery. The present study was designed to construct a polymer microsphere-encapsulated recombinant adenovirus with human tissue inhibitors of the matrix metalloproteinase-1 (TIMP-1) gene, and to discuss its characterization for the purpose of liver cancer gene therapy. The microsphere was prepared from biodegradable poly-DL-lactide-poly(ethylene glycol) (PELA) encapsulating rAdTIMP-1, the recombinant adenovirus carrying TIMP-1, by a modified double-emulsion method. The particle morphology, diameter, virus encapsulation, loading rate and release kinetics of the rAd-microspheres were determined in vitro. Hepatocellular carcinoma (HCC) HepG2 cells were transfected with the rAd-microsphere and the efficiency of transfection was assessed by fluorescent microscopy. The production and expression of TIMP-1 was identified by gelatin zymography and western blot analysis, and the invasiveness was detected by a matrigel matrix invasion assay. The microsphere encapsulating rAdTIMP-1 was successfully constructed with a diameter of 1.965 μm, encapsulation efficiency of 60.0%, a viral load of 10.5 x 10(8)/mg, a virus release of ~60% within 120 h and a total release time of >240 h. The resultant rAd-microspheres were able to efficiently transfect HepG2 cells with the transfection efficiency enhanced by ~90%. As a result, the transfected HepG2 cells had significantly increased TIMP-1 enzyme activity and the expression of TIMP-1 was detected by western blot analysis. In addition, the proliferation and invasion ability of the HCC cells was markedly inhibited by the rAd-microspheres. The resultant rAd-microspheres, PELA-encapsulated recombinant TIMP-1 adenovirus, had enhanced transfection efficiency and were able to markedly inhibit the in vitro biological behavior of HepG2 cells. This provides an experimental basis for this polymer application and may pave the way for prospective in vivo clinical trials and further comprehensive therapy for liver cancer.

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Section: Discussionsupporting

confidence: 73%

Section: Resultssupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Section: Experimental Animals Cell Lines and Culture Methodmentioning

confidence: 99%

Section: Experimental Animals Cell Lines and Culture Methodmentioning

confidence: 99%

See 3 more Smart Citations

Microencapsulation of recombinant adenovirus within poly-DL-lactide-poly(ethylene glycol) microspheres for enhanced gene transfection efficiency and inhibitory effects on hepatocellular carcinoma cells in vitro

Dong

Feng

et al. 2015

Molecular Medicine Reports

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Poly(lactic acid) Controlled Drug Delivery

Ding²,

Liu

et al. 2017

Industrial Applications of Poly(lactic Acid)

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Matrix Mediated Viral Gene Delivery: A Review

Steinhauff

Ghandehari

2019

Bioconjugate Chem.

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Polymeric matrices inherently protect viral vectors from preexisting immune conditions, limit dissemination to off-target sites, and can sustain vector release. Advancing methodologies in development of particulate based vehicles have led to improved encapsulation of viral vectors. Polymeric delivery systems have contributed to increasing cellular transduction, responsive release mechanisms, cellular infiltration, and cellular signaling. Synthetic polymers are easily customizable, and are capable of balancing matrix retention with cellular infiltration. Natural polymers contain inherent biorecognizable motifs adding therapeutic efficacy to the incorporated viral vector. Recombinant polymers use highly conserved motifs to carefully engineer matrices, allowing for precise design including elements of vector retention and responsive release mechanisms. Composite polymer systems provide opportunities to create matrices with unique properties. Carefully designed matrices can control spatiotemporal release patterns that synergize with approaches in regenerative medicine and antitumor therapies.

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Preparation of Microspheres Encapsulating a Recombinant TIMP-1 Adenovirus and their Inhibition of Proliferation of Hepatocellular Carcinoma Cells

Cited by 3 publications

References 21 publications

Microencapsulation of recombinant adenovirus within poly-DL-lactide-poly(ethylene glycol) microspheres for enhanced gene transfection efficiency and inhibitory effects on hepatocellular carcinoma cells in vitro

Microencapsulation of recombinant adenovirus within poly-DL-lactide-poly(ethylene glycol) microspheres for enhanced gene transfection efficiency and inhibitory effects on hepatocellular carcinoma cells in vitro

Poly(lactic acid) Controlled Drug Delivery

Matrix Mediated Viral Gene Delivery: A Review

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