Photochemical internalization-mediated nonviral gene transfection: polyamine core-shell nanoparticles as gene carrier

Zamora, Genesis; Wang, Frederick; Sun, Carlos; Trinidad, Anthony; Kwon, Young Jik; Cho, Soo Kyung; Berg, Kristian; Madsen, Steen J.; Hirschberg, Henry

doi:10.1117/1.jbo.19.10.105009

Cited by 21 publications

(12 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A modified form of PDT, photochemical internalization (PCI) has been shown to greatly enhance gene insertion efficiency for both viral as well as nonviral gene transfection protocols [16, 32, 33]. Due to the rapid attenuation of light in tissue this enhanced transfection efficiency would be limited to the illuminated targeted tumor site, thus avoiding transfection of off target normal tissue.…”

Section: Discussionmentioning

confidence: 99%

Photodynamic therapy enhances the efficacy of gene-directed enzyme prodrug therapy

Christie

Pomeroy

Nair

et al. 2017

Photodiagnosis and Photodynamic Therapy

Self Cite

View full text Add to dashboard Cite

Introduction Gene-directed enzyme prodrug therapy (GDEPT) employing the cytosine deaminase (CD) gene, which encodes an enzyme that converts the nontoxic agent 5-fluorocytosine (5-FC) into the chemotherapeutic drug 5-fluorouracil (5-FU), has shown promise both in experimental animals and in clinical trials. Nevertheless, with the transfection systems available presently the percentage of tumor cells incorporating the desired gene is usually too low for successful therapy. We have examined the ability of photodynamic therapy (PDT) to enhance the efficacy of the metabolites, converted from 5-FC by CD gene transfected rat glioma cells. Methods Hybrid tumor cell spheroids consisting of CD positive and CD negative F98 glioma cells in varying ratios were used as in vitro tumor models. PDT was performed with the photosensitizer AlPcS2a and λ = 670nm laser irradiance, both before and after confrontation with 5-FC. Results PDT increased the toxicity of 5-FU either as pure drug or derived from monolayers of CD positive cells chalanged with 5-FC. PDT in combination with 5-FC resulted in a significantly enhanced inhibition of hybrid spheroid growth compared to non light treated controls. This was the case even at tumor to producer cell ratios as high as 40:1. Conclusion The results of the present study show that GDEPT and PDT interact in a synergistic manner over a range of prodrug concentration and tumor to transfected cell ratios. The degree of synergy was significant regardless if PDT treatment was given before or after 5-FC administration. The highest degree of interaction was observed though, when PDT was delivered prior to prodrug exposure.

show abstract

Section: Discussionmentioning

confidence: 99%

Photodynamic therapy enhances the efficacy of gene-directed enzyme prodrug therapy

Christie

Pomeroy

Nair

et al. 2017

Photodiagnosis and Photodynamic Therapy

Self Cite

View full text Add to dashboard Cite

show abstract

“…Zamora et al prepared photochemical internalization mediated polyamine core–shell nanoparticles for tumor suppressor gene delivery. Their results showed that the prepared nanoparticles enhanced the delivery of tumor suppressor genes on U87 and U251 glioma cells [24]. Wang et al used core–shell nanoparticles for drug and gene co-delivery.…”

Section: Introductionmentioning

confidence: 99%

Cationic PEGylated polycaprolactone nanoparticles carrying post-operation docetaxel for glioma treatment

Varan¹,

Bilensoy²

2017

Beilstein J. Nanotechnol.

View full text Add to dashboard Cite

Background: Brain tumors are the most common tumors among adolescents. Although some chemotherapeutics are known to be effective against brain tumors based on cell culture studies, the same effect is not observed in clinical trials. For this reason, the development of drug delivery systems is important to treat brain tumors and prevent tumor recurrence. The aim of this study was to develop core–shell polymeric nanoparticles with positive charge by employing a chitosan coating. Additionally, an implantable formulation for the chemotherapeutic nanoparticles was developed as a bioadhesive film to be applied at the tumor site following surgical operation for brain glioma treatment. To obtain positively charged, implantable nanoparticles, the effects of preparation technique, chitosan coating concentration and presence of surfactants were evaluated to obtain optimal nanoparticles with a diameter of less than 100 nm and a net positive surface charge to facilitate cellular internalization of drug-loaded nanoparticles. Hydroxypropyl cellulose films were prepared to incorporate these nanoparticle dispersions to complete the implantable drug delivery system. Results: The diameter of core–shell nanoparticles were in the range of 70–270 nm, depending on the preparation technique, polymer type and coating. Moreover, the chitosan coating significantly altered the surface charge of the nanoparticles to net positive values of +30 to +50 mV. The model drug docetaxel was successfully loaded into all particles, and the drug release rate from the nanoparticles was slowed down to 48 h by dispersing the nanoparticles in a hydroxypropyl cellulose film. Cell culture studies revealed that docetaxel-loaded nanoparticles cause higher cytotoxicity compared to the free docetaxel solution in DMSO. Conclusion: Docetaxel-loaded nanoparticles dispersed in a bioadhesive film were shown to be suitable for application of chemotherapeutics directly to the action site during surgical operation. The system was found to release chemotherapeutics for several days at the tumor site and neighboring tissue. This can be suggested to result in a more effective brain tumor treatment when compared to chemotherapeutics administered as an intravenous bolus infusion.

show abstract

“…The resulting polyamine/PK core-shell nanoparticles have a gene-carrying polyamine/ DNA polyplex core shielded by PK shell, mimicking a viral vector consisting of a gene-carrying capsid core and an outer envelope. In the mildly acidic endosome, the outer PK shell hydrolyzes and releases the polyamine/DNA core weakening the endosomal membrane and increasing the effects of PCI [6]. We are presently studying the effects of PCI on Ma cell transfection employing these nanoparticles.…”

Section: Effects Of Pci On Gfp Transfection On U251/mamentioning

confidence: 97%

“…The concept of PCI is based on using light and photosensitzers to promote endosomal escape of trapped macro-molecules, thus avoiding lysosomal degradation [7,8]. In particular, packaging the gene polyplexes into acid degradable core shell NP (NP CD ) significantly enhanced the PCI gene transfection at low DNA and light levels [6,9]. …”

Section: Gene Therapy For Cancermentioning

confidence: 99%

“…Importantly, the bystander effect, where activated drug is exported from the transfected cells into the tumor microenvironment, plays an important role by inhibiting growth of adjacent tumor cells. We have recently published a series of studies employing photochemical internalization (PCI) enhanced gene transfection into glioma cells from human and rat [5,6]. The concept of PCI is based on using light and photosensitzers to promote endosomal escape of trapped macro-molecules, thus avoiding lysosomal degradation [7,8].…”

Section: Gene Therapy For Cancermentioning

confidence: 99%

See 1 more Smart Citation

Macrophage mediated PCI enhanced gene-directed enzyme prodrug therapy

et al. 2015

Self Cite

View full text Add to dashboard Cite

Photochemical internalization (PCI) is a photodynamic therapy-based approach for improving the delivery of macromolecules and genes into the cell cytosol. Prodrug activating gene therapy (suicide gene therapy) employing the transduction of the E. coli cytosine deaminase (CD) gene into tumor cells, is a promising method. Expression of this gene within the target cell produces an enzyme that converts the nontoxic prodrug, 5-FC, to the toxic metabolite, 5-fluorouracil (5-FU). 5-FC may be particularly suitable for brain tumors, because it can readily cross the bloodbrain barrier (BBB). In addition the bystander effect, where activated drug is exported from the transfected cancer cells into the tumor microenvironment, plays an important role by inhibiting growth of adjacent tumor cells. Tumor-associated macrophages (TAMs) are frequently found in and around glioblastomas. Monocytes or macrophages (Ma) loaded with drugs, nanoparticles or photosensitizers could therefore be used to target tumors by local synthesis of chemo attractive factors. The basic concept is to combine PCI, to enhance the ex vivo transfection of a suicide gene into Ma, employing specially designed core/shell NP as gene carrier.

show abstract

Photochemical internalization-mediated nonviral gene transfection: polyamine core-shell nanoparticles as gene carrier

Cited by 21 publications

References 41 publications

Photodynamic therapy enhances the efficacy of gene-directed enzyme prodrug therapy

Photodynamic therapy enhances the efficacy of gene-directed enzyme prodrug therapy

Cationic PEGylated polycaprolactone nanoparticles carrying post-operation docetaxel for glioma treatment

Macrophage mediated PCI enhanced gene-directed enzyme prodrug therapy

Contact Info

Product

Resources

About