Tumor-Homing, Size-Tunable Clustered Nanoparticles for Anticancer Therapeutics

Abstract

We present herein a pH-responsive dynamic DNA nanocluster based on gold nanoparticles with highly packed nucleic acid assembly and evaluate its potential as a drug delivery vehicle with tumor-specific accumulation. Each gold nanoparticle was readily functionalized with various functional DNA sequences; in particular, we modified the surface of gold nanoparticles with bcl-2 antisense and i-motif binding sequences. Clustering of the gold nanoparticles induced by hybridization of each DNA sequence via i-motif DNA provided tumor targeting and drug loading capabilities. After cellular uptake, the drug was released by disassembly of the gold nanoparticle cluster into single gold nanoparticles in response to the pH decrease in the late endosome. Furthermore, the antiapoptotic Bcl-2 protein was down-regulated by the antisense-modified gold nanoparticles; thus, drug-mediated apoptosis was significantly accelerated by sensitizing the cancer cells to the drug. Our size-tunable clustered nucleic acid-grafted gold nanoparticles provide tumor homing in the blood circulation and are thus a potential multifunctional therapeutic agent in vivo as well as in vitro.

Gold nanoclusters-assisted delivery of NGF siRNA for effective treatment of pancreatic cancer

“…GNCs with sizes smaller than 3 nm are relatively new as a class of gold nanomaterials, which show great promises in biological applications484950. In this study, cationic GNCs were developed with simply one-step reaction; moreover, the GNC–siRNA complexes do not require additional chemical modifications to facilitate entry into cells.…”

Antitumor therapeutic application of self-assembled RNAi-AuNP nanoconstructs: Combination of VEGF-RNAi and photothermal ablation

“…It is well known that AuNPs present different optical and resonance properties depending on their size; larger and bulkier AuNPs absorb at longer wavelengths than smaller or individual AuNPs 31. Therefore, this aspect elicits coupled surface plasmons and strong absorption at far-red and near infrared (NIR) wavelengths with efficient heat conversion 15, 21, 22. More precise observation of AuNPs was carried out through TEM imaging with and without uranyl acetate staining allowing observation of the spherical shape of PEI/RNAi-AuNPs and their precise nanostructure formations.…”

“…One of noticeable examples of these approach is a photothermal therapeutic application by utilizing AuNPs as a heat source as a result of efficient heat generation coming from strong absorption at far-red and near infrared (NIR) wavelengths 21-23. Therefore, more recent efforts have focused on constructing sophisticated AuNP and nucleic acid hybrid nano-assemblies engineered with great precision 15, 22. Most attempts have been concentrated on studying the dynamics or programmed behaviors of nano-assembly itself, especially the transition between two different configurations of the NPs translating into dynamic motion for switching on or off 24, 25.…”

Remission of lymphoblastic leukaemia in an intravascular fluidic environment by pliable drug carrier with a sliding target ligand

“…Different intracellular conditions such as pH1427, reductive potential16, enzymes28, and small molecules29 have been intensively examined as trigger discharging chemotherapeutic agents in programmed environments. We used pH–responsive “i–motif” DNA30 to induce the stimuli–responsive behaviour of the drug carrier3132.…”

“…We used pH–responsive “i–motif” DNA30 to induce the stimuli–responsive behaviour of the drug carrier3132. Unique double–stranded DNA (dsDNA) structure formed by the i–motif DNA and its complementary DNA responds to intracellular acidic environment33 and releases intercalated anti–cancer agent doxorubicin (DOX) by inducing its dissociation from the dsDNA27. By integrating these functions, we have developed an effective lymphocyte targeting drug carrier in circulating bloodstream environment (Fig.…”