Photothermal cancer therapy using near-infrared (NIR) laser radiation is an emerging treatment. In the NIR region, two biological transparency windows are located in 650-950 nm (first NIR window) and 1000-1350 nm (second NIR window) with optimal tissue transmission obtained from low scattering and energy absorption, thus providing maximum radiation penetration through tissue and minimizing autofluorescence. To date, intensive effort has resulted in the generation of various methods that can be used to shift the absorbance of nanomaterials to the 650-950 nm NIR regions for studying photoinduced therapy. However, NIR light absorbers smaller than 100 nm in the second NIR region have been scant. We report that a Au nanorod (NR) can be designed with a rod-in-shell (rattle-like) structure smaller than 100 nm that is tailored to be responsive to the first and second NIR windows, in which we can perform hyperthermia-based therapy. In vitro performance clearly displays high efficacy in the NIR photothermal destruction of cancer cells, showing large cell-damaged area beyond the laser-irradiated area. This marked phenomenon has made the rod-in-shell structure a promising hyperthermia agent for the in vivo photothermal ablation of solid tumors when activated using a continuous-wave 808 m (first NIR window) or a 1064 nm (second NIR window) diode laser. We tailored the UV-vis-NIR spectrum of the rod-in-shell structure by changing the gap distance between the Au NR core and the AuAg nanoshell, to evaluate the therapeutic effect of using a 1064 nm diode laser. Regarding the first NIR window with the use of an 808 nm diode laser, rod-in-shell particles exhibit a more effective anticancer efficacy in the laser ablation of solid tumors compared to Au NRs.

Construction of multifunctional nanoparticles (NPs) with near-infrared (NIR) plasmonic responses is considered a versatile and multifaceted platform for several biomedical applications. Herein, a double layer of Au/Ag alloy on the surface of truncated octahedral iron oxide NPs (IONPs) was prepared and the distance between the layers was controlled to exhibit broad and strong NIR absorption. The rattle-shaped IONP@shell-in-shell nanostructure showed light-response to the NIR biological window from 650 to 1300 nm for photothermal therapy (PTT) and magnetic guidance for hyperthermia and magnetic resonance imaging (MRI) diagnosis. Exposing the aqueous solution of IONP@shell-in-shell to a 1064 nm diode laser, its heat conversion efficiency was ∼28.3%. The in vitro cell viability at a gold concentration of 100 ppm was ∼85%, and decreased to ∼16% when the cells were treated with the NIR irradiation and magnetic attraction. T-weighted MRI images showed a clear accumulation of IONP@shell-in-shell at the tumor site with magnetic attraction. In vivo luminescence tumor images explained that the IONP@shell-in-shell could reduce the U87MG-luc2 cancer cell proliferation in mice with the NIR irradiation and magnetic attraction. These results indicate the IONP@shell-in-shell as a promising nanomedicine for PTT, magnetic targeting, and magnetic resonance imaging (MRI).

Combining upconversion nanoparticles (UCNPs) and UV-sensitive polymers to form a smart drug delivery system (DDS) is a promising strategy to circumvent drawbacks of direct UV excitation in clinical applications. This study tuned up core–shell UCNPs with a shell thickness of 6 nm and emission wavelength falling in the ultraviolet region at 350 nm under near-infrared (NIR) light irradiation at 980 nm. An amphiphilic block copolymer with UV-responsive o-nitrobenzyl ester (ONB) next to a glutathione (GSH)-responsive disulfide linkage was synthesized and formulated into a polymersome. Core–shell UCNPs and doxorubicin (DOX) were simultaneously encapsulated into the polymersome during double emulsion for DDS. The combination of NIR light-inducing photolysis of the ONB linkage and GSH cleaving the disulfide linkage enhanced DOX release for chemotherapy. From in vitro evaluation, the polymersome alone was nontoxic against three lung cancer cell lines, but the one loaded with core–shell UCNPs and DOX showed severe cell-killing effect under the assistance of a 980 nm diode laser. In vivo study in A549 tumor-bearing mice verified significant inhibition of tumor growth in mice treated with the polymersome containing core–shell UCNPs and DOX under 980 nm diode laser irradiation as compared with those without laser irradiation and those treated with free DOX. This intriguing nanomedicine of well-defined structures responsive to NIR light and reducing agents offers potential for smart DDS applications.

A novel dual-stimuli cleavable linker containing adjacent UV light-sensitive o-nitrobenzyl ester and GSH-responsive disulfide bonds was first designed and synthesized to increase the responsivity to external stimuli. The functionalized linker was then utilized to prepare a dual-responsive amphiphilic block copolymer using ring-opening polymerization and atom transfer radical polymerization. The copolymer formed a micelle in an aqueous solution and showed dual-stimuli responses including photo-mediated cleavage under UV light irradiation at 365 nm as well as reduction-responsive degradation in the presence of a reducing agent. The micelle was nontoxic against three cell lines and majorly internalized via clathrin-mediated endocytosis. Doxorubicin (Dox) was loaded in the hydrophobic core of the micelle. Enhancement of a cell-killing effect against A549 cells was clearly observed in the Dox-encapsulated micelle when exposed to UV light.

Background To improve responses to tumor microenvironments for achieving a better therapeutic outcome in combination cancer therapy, poly(ε-caprolactone)-SS-poly(methacrylic acid) diblock copolymer (PCL-SS-PMAA) with a disulfide linkage between the hydrophobic and hydrophilic junctions was synthesized. Materials and Methods Repeating units of PCL and PMAA in PCL-SS-PMAA were controlled and formulated into polymersomes (PSPps). Truncated octahedral Fe 3 O 4 nanoparticles (IONPs) were synthesized and encapsulated to produce IONPs-PSPps NPs and doxorubicin (DOX) was further loaded to produce IONPs-PSPps@DOX NPs for theranostic applications. Results IONPs-PSPps NPs remained a superparamagnetic property with a saturation magnetization value of 85 emu⋅g Fe3O4 −1 and a relaxivity value of 180 mM −1 ⋅s −1 . Upon exposure to an alternating magnetic field (AMF), IONPs-PSPps NPs increased temperature from 25°C to 54°C within 15 min. Among test groups, the cell apoptosis was greatest in the group exposed to IONPs-PSPps@DOX NPs with AMF and magnet assistance. In vivo T 2 -weighted magnetic resonance images of A549 tumor-bearing mice also showed highest contrast and greatest tumor suppression in the tumor with AMF and magnet assistance. Conclusion IONPs-PSPps@DOX NPs are a potential theranostic agent having multifaceted applications involving magnetic targeting, MRI diagnosis, hyperthermia and chemotherapy.