TiO₂-Capped Gold Nanorods for Plasmon-Enhanced Production of Reactive Oxygen Species and Photothermal Delivery of Chemotherapeutic Agents

Abstract

Near infrared (NIR)-absorbing noble metal nanostructures are being extensively studied as theranostic agents, in particular for photoacoustic imaging and photothermal therapy. Because of the electric field enhancement at the tips of anisotropic metal nanostructures, positioning photoactive species at these sites can lead to increased energy absorption. Herein, we show the site-specific placement of NIR-active photosensitizers at the ends of gold nanorods (AuNRs) by growing porous TiO caps. The surface plasmon resonance of the AuNRs was carefully tuned to overlap with the exciton absorption of indocyanine green (ICG), a NIR photosensitizer with low quantum yields and poor photostability. In conjugating high amounts of ICG to the TiO caps, increased amounts of singlet oxygen (O) were generated as compared to when ICG was attached to sidewalls of the AuNRs. Because the AuNRs also cause local increases in temperature upon NIR excitation, DNA strands were next attached to the AuNRs sidewalls and loaded with doxorubicin (DOX). We found that the synergistic effect of increased O and photothermal-induced drug delivery led to significant improvements in tumor cell killing. This work demonstrates that with careful design over hybrid nanostructure synthesis, higher levels of tumor therapy may be achieved.

<p>Pathological Mechanism of Photodynamic Therapy and Photothermal Therapy Based on Nanoparticles</p>

“…By connecting the photosensitizer with the cell’s AuNRs uptake, stimulating the irradiation of the photosensitizer can produce PDT effect, so different effects can be selectively controlled by controlling the intensity of the light source. 39 If we choose the excitation wavelength that can excite the photosensitizer and LSP resonance at the same time, the PTT and PDT effects will be produced synchronously, thus further destroying the target cells. 40 Ding et al designed Au-Cu9S5, an LSP-enhanced light absorption cross section, applicating of PTT principle, has the thermosensitive nanomaterial potential and imaging ability of X-ray CT. 41 …”

TiO2‐Based Photocatalysis at the Interface with Biology and Biomedicine

“…The gold‐plasmonic photogenerated heat can also be used synergistically with the production of ROS in the cancer‐cell‐killing activity of Au−TiO 2 nanocomposites . For instance, a novel plasmon‐enhanced PDT‐ and photothermal therapy (PTT)‐controlled drug‐release system for cancer cell therapy has been recently presented . Indocyanine green (ICG) has been used as the NIR PS conjugated site‐specifically at the ends of AuNRs.…”

“…[88] For instance, a novel plasmon-enhanced PDT-a nd photothermalt herapy (PTT)-controlled drug-releases ystem for cancerc ell therapy has been recently presented. [89] Indocyanineg reen (ICG) has been used as the NIR PS conjugated site-specifically at the ends of AuNRs. The SPR of the AuNRs is carefullyt uned to overlap with the excitona bsorption of ICG.…”

“…Next, ICG was sitespecifically attached to TiO 2 by first reacting with dopaminefollowed by NHS-DBCO (NHS: N-hydroxysuccinimide, DBCO: dibenzocyclooctyne) and azide-functionalized ICG. ICG-conjugatedAuNR@TiO 2 was next reacted with thiolated ICG-containing DNA strands thatw ere then loaded with DOX.R eprinted with permission from ref [89]. Copyright:2018, American Chemical Society.…”

3D Lattice Engineering of Nanoparticles by DNA Shells

“…According to the position of “DNA patches”, different lattices could be designed accordingly. He et al successfully obtained patchy nanorods with DNA only in the middle of the rods while the two ends were blocked . Chao and co‐workers could functionalize different DNA sequences on designed positions on the gold nanorod with the help of DNA origami structures .…”