Unprecedented “All‐in‐One” Lanthanide‐Doped Mesoporous Silica Frameworks for Fluorescence/MR Imaging and Combination of NIR Light Triggered Chemo‐Photodynamic Therapy of Tumors

Abstract

Designing a single multifunctional nanoparticle that can simultaneously impart both diagnostic and therapeutic functions is considered to be a long‐lasting hurdle for biomedical researchers. Conventionally, a multifunctional nanoparticle can be constructed by integrating organic dyes/magnetic nanoparticles to impart diagnostic functions and anticancer drugs/photosensitizers to achieve therapeutic outcomes. These multicomponents systems usually suffer from severe photobleaching problems and cannot be activated by near‐infrared (NIR) light. Here, it is demonstrated that all‐in‐one lanthanide‐doped mesoporous silica frameworks (EuGdOx@MSF) loaded with an anticancer drug, doxorubicin (DOX) can facilitate simultaneous bimodal magnetic resonance (MR) imaging with approximately twofold higher T1‐MR contrast as compared to the commercial Gd(III)‐DTPA complex and fluorescence imaging with excellent photostability. Upon a very low dose (130 mW cm−2) of NIR light (980 nm) irradiation, the EuGdOx@MSF not only can sensitize formation of singlet oxygen (1O2) by itself but also can phototrigger the release of the DOX payload effectively to exert combined chemo‐photodynamic therapeutic (PDT) effects and destroy solid tumors in mice completely. It is also discovered for the first time that the EuGdOx@MSF‐mediated PDT effect can suppress the level of the key drug resistant protein, i.e., p‐glycoprotein (p‐gp) and help alleviate the drug resistant problem commonly associated with many cancers.

Near‐Infrared‐Light‐Activatable Nanomaterial‐Mediated Phototheranostic Nanomedicines: An Emerging Paradigm for Cancer Treatment

“…These EuGdOx@MSF nanostructures were used as intrinsic fluorescence cellular markers, MR contrast reagents, drug delivery reagents, and NIR‐light‐activatable NmPDT reagents for complete destruction of tumors under ultralow laser doses (980 nm; 130 mW cm −2 ) of NIR light irradiation. The ability of EuGdOx@MSF nanostructures activated using 980 nm NIR light offers an effective therapeutic treatment option for treating deeply seated tumors along with their inherent dual modal imaging capabilities as diagnostic options simultaneously ( Figure ) . Overall, most of the inorganic nanomaterials discussed in this section show excellent NmPDT capabilities in achieving complete destruction of tumors operated using ultralow doses of NIR light with low/negligible short‐term cytotoxicities.…”

“…Besides liposomes, many other NIR light absorbing nanocarriers were also reported, including PEGylated hollow gold nanospheres (800 nm, 1.0–5.0 W cm −2 , 5 min irradiation, DOX release), Aptamer gated‐Au NR@porous SiO 2 shell (808 nm, 0.6–1.2 W cm −2 , 10 min, DOX release), hybridized UCNP‐hydrogel (980 nm, 3.1–5 W, 0–3 h, proteins/enzyme release), etc. The advantages to use light‐absorbing nanomaterials/nanocarriers to absorb NIR light and trigger drug release include large extinction coefficients, and abilities to achieve high local temperature rise or generation of ROS to achieve combined chemo‐photothermal or chemo‐photodyanmic therapies for successful eradication of solid tumors in in vivo mice experiments . The effect of NIR‐light‐triggered drug release is similar to temperature‐induced drug release except that the local temperature rise was achieved via the utilization of NIR light absorbing nanospecies in a spatial‐temporally controlled manner.…”

“…Schematic representation of the multifunctional lanthanide doped mesoporous silica (EuGdOx@MSF‐DOX)‐ based theranostic platform for multimodal imaging and near infrared‐light‐triggered combination of chemo‐photodynamic therapy. Reproduced with permission . Copyright 2016, Wiley‐VCH.…”

Recent Progress in Near Infrared Light Triggered Photodynamic Therapy

“…Other emerging inorganic nanoparticles exploited for NIR light activated PDT, such as lanthanide‐doped mesoporous silica frameworks (EuGdO x @MSF), NaYbF 4 NPs, Cs x WO 3 nanorods, and Cu 2 (OH)PO 4 quantum dots (QDs), have been brought to the light. Table 2 shows recent examples of inorganic nanoparticles applicable for NIR light activated PDT.…”

Cascade‐amplification of therapeutic efficacy: An emerging opportunity in cancer treatment

“…In addition to the direct damage to tumor cells, the generated ROS could also destroy those key proteins that are related to the development of drug resistance, such as p‐glycoprotein (p‐gp) (Fan, Huang, & Chen, ; He, Liu, & Lin, ). A good example in this regard was published by Kalluru et al (), in which the authors loaded doxorubicin into lanthanide‐doped mesoporous silica frameworks (EuGdOx@MSF) (Figure ). Under NIR laser with low power density, the EuGdOx@MSF could generate ROS and reduce the amount of p‐glycoprotein on the tumor cell membrane, in addition to the usual PDT damage to the tumor cells.…”