Oligonucleotides—Assembled Au Nanorod-Assisted Cancer Photothermal Ablation and Combination Chemotherapy with Targeted Dual-Drug Delivery of Doxorubicin and Cisplatin Prodrug

Abstract

External stimuli responsive dual drugs carrier was synthesized with Au nanorods (NRs) as the platform. On Au NRs, single stranded DNAs were assembled using 5' thiol end. Following this, complementary DNA (cDNA) strands were hybridized. This hybridized double stranded DNA facilitated doxorubicin (Dox) intercalation into the duplexes. The cDNA designed with the 5' amine functional group assisted to tether platinum [Pt(IV)] prodrugs by establishing amide bond with the acid group at the axial ligand. The other axial acid group in Pt(IV) prodrugs was conjugated with the folic acid (FA) to target folate receptors overexpressed in the cancer cells. This targeting vehicle provided remote-controlled delivery of this high toxic cargo cocktail at the tumor site, ensuring extra specificity that can avoid acute toxicity, where release of Dox and Pt(IV) was achieved upon NIR 808 nm diode laser irradiation. The dehybridization set the Dox free to bind the cell nucleus and cellular reductants reduced Pt(IV) to yield toxic Pt(II), becoming an active drug. The in vitro and in vivo studies revealed that this external stimulus responsive combination drug delivery was significantly effective.

End-to-end self-assembly of gold nanorods in isopropanol solution: experimental and theoretical studies

“…So far, there have been well-described biological molecule-based pathways of assembling NRs where the process took place in water. The linking schemes involved proteins (Hamon et al 2014 ; Wang and Tang 2014 ), streptavidin–biotin interactions (Caswell et al 2003 ; Gole and Murphy 2005 ), DNA with thiol groups (Dujardin et al 2001 ; Shanmugam et al 2014 ; Thomas et al 2004 ), or co-operative hydrogen-bonding schemes based on thiolated molecules (Thomas et al 2004 ). However, all these procedures require additional stages of time-consuming functionalization as well as careful control of pH and salt concentration.…”

Multifunctional platinum‐based nanoparticles for biomedical applications

“…Indeed, co‐administration of cisplatin with TOP2‐inhibitors has shown greatly enhanced activity in cancer cells, in vivo murine models, and also in a phase III clinical trial in endometrial carcinoma. Nanoparticle‐based delivery platform can further improve the therapeutic efficacy and reduce side effects of the combination therapy regiment . Nguyen and coworkers developed a polymer‐caged nanobin encapsulating cisplatin and doxorubicin (Pt‐PCN DXR ) .…”

“…In a nanoporous particle‐supported lipid bilayer system, the combination of therapeutic agents (e.g., drugs, small interfering RNA, and toxins) and diagnostic agents (e.g., quantum dots) and simultaneous tumor targeting, endosomal escape and nuclear accumulation of selected cargos were achieved synergistically . Similar multifunctional nanoparticles have been used in a number of platinum drug delivery systems for great efficacy and reduced side effects (Figure ) …”

Novel delivery approaches for cancer therapeutics

“…Several enzyme cleavable peptide prodrug conjugates and formulations of DOX have been recently developed to increase the specificity and tolerability of chemotherapeutic agents [197–205]. Selective DOX prodrug activation using photoirradiation [206], pH active linkages [176, 207–209], photothermal linkages [210], and reduction [211] have paved the way for the development of new selective chemotherapeutic agents.…”