How to study dendriplexes I: Characterization

Shcharbin, Dzmitry; Pedziwiatr, Elzbieta; Bryszewska, Maria

doi:10.1016/j.jconrel.2009.01.015

Cited by 79 publications

(64 citation statements)

References 83 publications

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“…However, the in vivo morphology of the complexes could be different from the ones seen by TEM, as sample preparation for TEM involves drying which might induce aggregation of the complexes and alterations in their morphology. 22 The TEM images, however, yielded direct evidence of the ability of PETIM to complex with and condense pIRES-Rgp and an approximation of the dendriplex morphology in the dry state.…”

mentioning

confidence: 98%

Enhancement of immunogenicity and efficacy of a plasmid DNA rabies vaccine by nanoformulation with a fourth-generation amine-terminated poly(ether imine) dendrimer

Ullas¹,

Madhusudana²,

Desai³

et al. 2014

IJN

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Purpose Delayed onset of, and low magnitude of, protective immune responses are major drawbacks limiting the practical utility of plasmid vaccination against rabies. In this study we evaluated whether nanoformulation with the novel poly(ether imine) (PETIM) dendrimer can enhance the immunogenicity and efficacy of a plasmid-based rabies vaccine. Materials and methods A plasmid vaccine construct (pIRES-Rgp) was prepared by cloning the full-length rabies virus glycoprotein gene into pIRES vector. Drawing upon the results of our previous study, a dendriplex (dendrimer-DNA complex) of pIRES-Rgp was made with PETIM dendrimer (10:1 w/w, PETIM:pIRES-Rgp). In vitro transfection was done on baby hamster kidney (BHK)-21 cells to evaluate expression of glycoprotein gene from pIRES-Rgp and PETIM-pIRES-Rgp. Subsequently, groups of Swiss albino mice were immunized intramuscularly with pIRES-Rgp or PETIM-pIRES-Rgp. A commercially available cell culture rabies vaccine was included for comparison. Rabies virus neutralizing antibody (RVNA) titers in the immune sera were evaluated on days 14, 28, and 90 by rapid fluorescent focus inhibition test. Finally, an intracerebral challenge study using a challenge virus standard strain of rabies virus was done to evaluate the protective efficacy of the formulations. Results Protective levels of RVNA titer (≥0.5 IU/mL) were observed by day 14 in animals immunized with pIRES-Rgp and its dendriplex. Notably, PETIM-pIRES-Rgp produced 4.5-fold higher RVNA titers compared to pIRES-Rgp at this time point. All mice immunized with the PETIM-pIRES-Rgp survived the intracerebral rabies virus challenge, compared with 60% in the group which received pIRES-Rgp. Conclusion Our results suggest that nanoformulation with PETIM dendrimer can produce an earlier onset of a high-titered protective antibody response to a plasmid-based rabies vaccine. PETIM dendriplexing appears to be an efficacious nonviral delivery strategy to enhance genetic vaccination.

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confidence: 98%

Enhancement of immunogenicity and efficacy of a plasmid DNA rabies vaccine by nanoformulation with a fourth-generation amine-terminated poly(ether imine) dendrimer

Ullas¹,

Madhusudana²,

Desai³

et al. 2014

IJN

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“…To observe the particle morphology and size, the PAMAM G4-RRLR/pDNA polyplexes (24:1, w/v) were observed using transmission electron microscopy. 15,16 As shown in Figure 5, polyplexes were represented round. Although their mean diameter was not similar to those measured using dynamic light scattering, we could elucidate the approximate size of polyplexes and the discrepancy in these results from different methods might be due to condensation between polyplexes during the airdrying process.…”

Section: Resultsmentioning

confidence: 99%

PAMAM Dendrimer Conjugated with N-terminal Oligopeptides of Mouse Fibroblast Growth Factor 3 as a Novel Gene Carrier

Jung¹,

Lee²,

Yang³

et al. 2014

Bulletin of the Korean Chemical Society

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In this study, we introduced the RRLR oligopeptide sequences on the surface of polyamidoamine (PAMAM) dendrimer and characterized the physical properties and gene carrier activity of the novel polymer using HEK 293, NIH3T3, and HeLa cells. The RRLR peptide sequences were derived from a mouse fibroblast growth factor 3 (FGF3) protein containing a bipartite NLS motif. The entire sequence of FGF3 is RLRRDAGGRGGVYEHLGGAPRRRK and it has two functional sequences RLRR and RRRK at Nterminus and C-terminus, respectively. In particular, PAMAM G4-RRLR conferred enhanced transfection efficiency and lower cytotoxicity compared with those of PEI 25 kDa, PAMAM G4-R, and PAMAM G4 in various cell lines. These results suggest that the introduction of N-terminal oligopeptides of FGF3 on the surface of PAMAM holds promise as an effective non-viral gene delivery carrier for gene therapy.

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“…There are many reports presenting promising results in the topic of nucleic acids delivery using complexes called 'dendriplexes' [93][94][95]. Among variety of proposed candidates, PAMAM dendrimers are the most explored dendrimers type, followed by poly(propylene imine) (PPI) dendrimers, poly(l-lysine) (PLL) dendrimers, and some others [96].…”

Section: Clinical Studies Of Dendrimers For Targeted Cancer Therapymentioning

confidence: 99%

Dendrimers as Drug Nanocarriers: The Future of Gene Therapy and Targeted Therapies in Cancer

Franiak-Pietryga¹,

Ziemba²,

Messmer³

et al. 2018

Dendrimers - Fundamentals and Applications

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Synthetic polymers, such as dendrimers, play a critical role in pharmaceutical discovery and development. Advances in the application of nanotechnology in medicine have given rise to multifunctional "smart" nanocarriers that can deliver one or more therapeutic agents safely and selectively to cancer cells, including intracellular gene-specific targeting. Dendrimers with their 3D nanopolymeric architectures are highly attractive class of drug and gene delivery vector. Advances in understanding and manipulating genes gave scientists a tool to make changes in people DNA to prevent or treat diseases. Over the past decade, gene therapy has been in use in clinical trials. The inactivation of the tumor suppressor genes is the main idea of the development of gene therapy in the cancer treatment. Broad spectrum of delivery concepts, including viral vectors, liposomes, cationic polymers and dendrimers, cell-penetrating peptides and gold and magnetic nanoparticles have been investigated. A well-designed vector is the most desirable approach to increase the safety of gene therapy, which is still in its infancy stages in cancer research. More experimental and clinical trials are focused on well-designed and effective doses of vectors that are essential for therapeutic efficacy of gene therapy for its potential in clinical use against a wide variety of cancers.

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How to study dendriplexes I: Characterization

Cited by 79 publications

References 83 publications

Enhancement of immunogenicity and efficacy of a plasmid DNA rabies vaccine by nanoformulation with a fourth-generation amine-terminated poly(ether imine) dendrimer

Enhancement of immunogenicity and efficacy of a plasmid DNA rabies vaccine by nanoformulation with a fourth-generation amine-terminated poly(ether imine) dendrimer

PAMAM Dendrimer Conjugated with N-terminal Oligopeptides of Mouse Fibroblast Growth Factor 3 as a Novel Gene Carrier

Dendrimers as Drug Nanocarriers: The Future of Gene Therapy and Targeted Therapies in Cancer

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