Computer Simulation of DNA Condensation by PAMAM Dendrimer

Abstract

In this study, dissipative particle dynamics is employed to investigate the complexation of poly(amido amine) dendrimer and single‐stranded DNA (ssDNA). A coarse‐grained model for ssDNA is constructed, which reproduces correctly the conformational behavior of the ssDNA molecules. The effects of pH, dendrimer generation, ionic strength, and dendrimer/ssDNA charge ratio on DNA–dendrimer complexes are explored. Simulation results show that ssDNA molecules can be significantly condensed by dendrimers and stable complexes are obtained by regulating the pH value. The ssDNA chain penetration would complicate its release from dendrimer, while this can be tuned by different generations of dendrimer. Salt concentration affects the size and stability of the complexes through ion screening effect. Dendrimer/ssDNA charge ratio can be used to control the size and morphology of the complex. This work can help design dendrimer‐based gene vectors.

PAMAM dendrimers as efficient drug and gene delivery nanosystems for cancer therapy

“…One well-known example is the Arg-Gly-Asp (RGD) peptide, which has a strong affinity to αvβ3 integrin, which is expressed at high levels on the surface of tumor microvasculature as well as some cancer cells [85]. In 2016 [86], Ma and co-workers investigated a peptide called RGD-TAT (RGD attached to amino acids 49–57 of the HIV TAT protein that functions as a “cell penetrating peptide”) and attached it to G4 PAMAM to produce a new RGD-TAT-PEG-PAMAM (RTPP) nanocarrier that could encapsulate methotrexate (MTX) as a model drug. In vitro targeting ability of the complexes was studied in HepG2 and MCF7 cells (expressing αvβ3 integrin at high and low levels respectively) was studied using a fluorescent indicator.…”

“…In vitro targeting ability of the complexes was studied in HepG2 and MCF7 cells (expressing αvβ3 integrin at high and low levels respectively) was studied using a fluorescent indicator. Their results showed that HepG2 cells (over-expressing αvβ3 compared to MCF7cells) showed higher cytotoxicity due to a combination of RGD recognition and the TAT cell-penetrating ability [86]. Effective delivery of anticancer drugs to brain tumors is difficult because of limited penetration through the “blood-brain-barrier” (BBB).…”

“…Furthermore, it is proposed that the positively charged amine groups on the dendrimer and phosphate groups of the DNA play the main role in these interactions. Since PAMAM dendrimers is responsible for inducing DNA condensation and different wrapping around, it needs further investigation for gene delivery purposes [86–88]. To address this phenomenon, different structural techniques including circular dichroism (CD), Fourier transform infrared (FTIR), UV–visible spectroscopic methods and atomic force microscopy (AFM) were used by Froehlich and coworkers to analyze the binding site between calf-thymus DNA and mPEG-PAMAM-G3, mPEG-PAMAM-G4 and PAMAM-G4 dendrimers as the models.…”

Multiscale Modeling and Simulation of Nano‐Carriers Delivery through Biological Barriers—A Review

“…In addition to biopolymers, some other nanomaterials have been proposed as the drug carriers with controllable release efficiency and high loading capability. For example, Su et al . pointed that as gene delivery carriers, PAMAM dendrimers can compact the single‐stranded DNA (ssDNA) significantly at neutral or low pH value.…”

“…The interaction between NCs and drug molecules, which determines the containment and release of drugs, becomes a key in drug delivery technique. Generally, in order to enhance the loading content and release efficiency, the drug molecules are loaded into carriers via hydrophobic interactions, electrostatic interactions, hydrogen bonding, π–π stacking, and covalent interactions . By engineering hydrophobic interaction between protein‐based NCs and small guest molecules, Ren et al .…”