Biodegradable Silica‐Based Nanotheranostics for Precise MRI/NIR‐II Fluorescence Imaging and Self‐Reinforcing Antitumor Therapy

Abstract

cancer diagnosis including higher spatial and temporal resolution than the conventional NIR-I window fluorescence imaging (650-900 nm), mainly benefiting from the simultaneously suppressed tissue auto-fluorescence, photon scattering, and background interference. [3-5] In spite of significant improvements in NIR-II FL for imaging performance, accurate and wealthy information at different tissue penetration depths and scales cannot be effectively provided by a single imaging technology. [6,7] Magnetic resonance imaging (MRI) has outstanding performance in modern clinical medicine, offering higher spatial resolution than that of NIR-II FL. [8,9] Considering the desirable features of each imaging modality, integration of NIR-II FL and MRI may accurately delineate tumor by compensating their inherent limitations. Therefore, there is an urgent demand for an efficient imaging tool to achieve precise MRI/NIR-II FL dual-modal imaging of tumors. With the rapid development of biomedical engineering and nanotechnology, a variety of multimodal nanoprobes have been developed and provide accurate location and therapeutic improvement of tumor. [10-12] To date, most research has been focused on the rational design and fabrication of an all-in-one nanotheranostic as an extremely valuable strategy with multifunctional theranostic performance. [13,14] Wang and co-workers designed a novel small-molecule dye DPP-BT, which showed a single NIR laser triggered multifunctional properties for NIR-II fluorescence/photoacoustic (PA) Multi-modality cancer diagnosis techniques based on the second near-infrared window fluorescence (NIR-II FL, 1000-1700 nm) imaging have become the focus of research attention. For such multimodality probes, how to take advantage of the tumor microenvironments (TME) characteristics to better image diseases and combine efficient therapeutics to achieve theranostics is still a big challenge. Herein, a novel TME-activated nanosystem (FMSN-MnO 2-BCQ) employing degradable silica-based nanoplatform is designed, adjusting the ratio of intratumoral hydrogen peroxide (H 2 O 2)/glutathione (GSH) for magnetic resonance imaging (MRI)/NIR-II FL imaging and selfreinforcing chemodynamic therapy (CDT). Innovative bovine serum albumin (BSA)-modified fusiform-like mesoporous silica nanoparticles (FMSN) is fabricated as a carrier for NIR-II small molecule (CQ4T) and MRI reporter MnO 2. Remarkably, the BSA modification helped to achieve the dual-functions of high biocompatibility and enhance NIR-II fluorescence. The FMSN-MnO 2-BCQ with FMSN framework featuring a stepwise degradability in tumor interior released MnO 2 and BCQ nanoparticles. Through the specific degradation of MnO 2 by the TME, the produced Mn 2+ ions are effectively exerted Fenton-like activity to generate hydroxyl radical (•OH) from endogenous H 2 O 2 to eradicate tumor cells. More importantly, the GSH depletion due to the synergistic effect of tetrasulfide bond and MnO 2 in turn induced the oxidative cytotoxicity for self-reinforcing CDT.

Chemodynamic Therapy via Fenton and Fenton‐Like Nanomaterials: Strategies and Recent Advances

“…Effective introduction of HCO 3 − in the nanosystems should be one of the ways to improve the Mn‐involved CDT effects. Besides, the Mn 2+ generated in the above process is generally regarded as an MRI reagent, [ 276 ] which makes Mn‐containing CDT nanomaterials potential theranostic platforms.…”

“…[ 205,274 ] Importantly, manganese oxides can provide many advantages for tumor therapy, including optimal performance in near‐neutral conditions and selective production of ROS. [ 205 ] Thus, Mn‐based nanomaterials have been used for CDT, [ 275–279 ] some of which are listed in Table 2. For example, Cao et al.…”

“…designed a nanosystem for MRI/NIR‐II FL imaging and self‐reinforced CDT. [ 276 ] The fusiform‐like mesoporous silica NPs (FMSN) with a hierarchical pore structure were prepared through a dual‐template (BSA and cetyltrimethylammonium bromide, CTAB) mediated strategy based on a sol–gel method. Then MnO 2 was formed in the FMSN via a redox reaction of KMnO 4 to generate FMSN‐MnO 2 .…”

Near-Infrared Inorganic Nanomaterials for Precise Diagnosis and Therapy

“…How to take advantage of the tumor microenvironments characteristics to better image diseases and combine efficient therapeutics is still a challenge. To solve this problem, Zheng et al (2021) have developed the FMSN-MnO 2 -BCQ biodegradable nanoplatforms, with TME-activated tumor-deep delivery performance for accurate imaging and self-reinforcing CDT ( Figure 9Ai ) . In 2020, Chen et al (2020c) have successfully prepared a NIR-light triggered ratio metric fluorescent nanoplatform composed of UCNPs, DOX, and photosensitive block copolymer PEG-b-P(NBA-co-NBANA) ( Figure 9Aii ) .…”

“… An illustrated summary of significant CDT, PDT, PTT (A) (i) Schematic illustration of FMSN-MnO 2 -BCQ for dual-mode imaging and self-reinforcing CDT ( Zheng et al, 2021 ). Reproduced with permission from Zheng et al (2021) . (ii) NIR-light-regulated fluorescence imaging and chemotherapy ( Chen et al, 2020a ).…”