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.

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Ultrasound techniques have been extensively employed for diagnostic purposes. Because of its features of low cost, easy access, and noninvasive real-time imaging, toward clinical practice it is highly anticipated to simply use diagnostic ultrasound to concurrently perform imaging and therapy. We report a H2O2-filled polymersome to display echogenic reflectivity and reactive oxygen species-mediated cancer therapy simply triggered by the microultrasound diagnostic system accompanied by MR imaging. Instead of filling common perfluorocarbons, the encapsulation of H2O2 in H2O2/Fe3O4-PLGA polymersome provides O2 as the echogenic source and (•)OH as the therapeutic element. On exposure to ultrasound, the polymersome can be easily disrupted to yield (•)OH through the Fenton reaction by reaction of H2O2 and Fe3O4. We showed that malignant tumors can be completely removed in a nonthermal process.

The major challenge in current chemotherapy is to increase local effective therapeutic concentration of drugs as well as to minimize toxicity and side effects for patients. The targeted delivery of drugs to their desired site of action in a controlled manner plays an essential role in the development of drug formulations. A photocage refers to a caged molecule rendered biologically inert by a photolabile protecting group. Molecules are illuminated with light to liberate the caged group and then become active forms. In this study, we formulate upconversion nanoparticles (UCNPs) as the NIR-triggered targeting and drug delivery vehicles that successfully deliver in vitro and in vivo for near-infrared light photocontrolled targeting, bioimaging, and chemotherapy. It is noted that there has been no report on the systemic administration UCNP-based drug delivery agents for evaluation of bioimaging and chemotherapy. To achieve phototargeting, the tumor-homing agent (i.e., folic acid) has been constructed as a photoresponsive molecule. For the chemotherapeutic effect, the antitumor drug doxorubicin is thiolated on the surface of UCNPs, forming a disulfide bond that can be cleaved by lysosomal enzymes within the cells. The caged UNCPs can serve as a platform for the improvement of selective targeting and possible reduction of adverse side effects from chemotherapy.

The hypoxia region in a solid tumor has been recognized as a complex microenvironment revealing very low oxygen concentration and deficient nutrients. The hypoxic environment reduces the susceptibility of the cancer cells to anticancer drugs, low response of free radicals, and less proliferation of cancer cells in the center of the solid tumors. However, the reduced oxygen surroundings provide an appreciable habitat for anaerobic bacteria to colonize. Here, we present the bacteria-mediated targeting hypoxia to offer the expandable spectra for diagnosis and therapy in cancer diseases. Two delivery approaches involving a cargo-carrying method and an antibody-directed method were designed to deliver upconversion nanorods for imaging and Au nanorods for photothermal ablation upon near-infrared light excitation for two forms of the anaerobic Bifidobacterium breve and Clostridium difficile. The antibody-directed strategy shows the most effective treatment giving stronger imaging and longer retention period and effective therapy to completely remove tumors.