Magnetic resonance imaging (MRI) is one of the most widely used diagnostic tools in the clinic. To improve imaging quality, MRI contrast agents, which can modulate local T1 and T2 relaxation times, are often injected prior to or during MRI scans. However, clinically used contrast agents, including Gd3+-based chelates and iron oxide nanoparticles (IONPs), afford mediocre contrast abilities. To address this issue, there has been extensive research on developing alternative MRI contrast agents with superior r1 and r2 relaxivities. These efforts are facilitated by the fast progress in nanotechnology, which allows for preparation of magnetic nanoparticles (NPs) with varied size, shape, crystallinity, and composition. Studies suggest that surface coatings can also largely affect T1 and T2 relaxations and can be tailored in favor of a high r1 or r2. However, the surface impact of NPs has been less emphasized. Herein, we review recent progress on developing NP-based T1 and T2 contrast agents, with a focus on the surface impact.

A promising theranostic platform for solid tumors would deliver and release anticancer nanomedicine effectively in tumor cells. However, diverse biological barriers, especially related to the tumor microenvironment, impede these theranostic agents from reaching the tumor cell. Herein, a sequential pH and reduction-responsive polymer and gold nanorod (AuNR) core-shell assembly to overcome these barriers via a two-stage size decrease and disassembly of the nano platform responding to the specified tumor microenvironment are reported. The tumor uptake of the hybrid nanoparticle (NP) is 14.2% ID g −1 , which is two and four times higher than the noneresponsive hybrid NPs and small AuNR@PEG, respectively. After tumor uptake of the hybrid NPs, the disassembled ultrasmall AuNRs coated with a polymer of polymerized reduction-responsive doxorubicin (DOX) prodrug monomers penetrate into the solid tumor and lead to localized DOX release in the tumor cell. A linear increase in photoacustic (PA) effects from the PA activating polymer on an AuNR cluster surface indicates a critical role of electromagnetic fields in the AuNR assembly, which is consistent with the theoretical calculation results. Furthermore, the hybrid NP can serve as a promising deep-tissue PA and surfaceenhanced Raman scattering imaging agent for real-time in vivo investigation of physiological behaviors and deep tumor penetrating nanotherapy effects.

Fluorescence (FL) imaging in the second near-infrared window (NIR-II, 1000–1700 nm) has emerged as a promising bioimaging modality that enables noninvasive visualization of deep tissue with an unprecedented resolution. However, there is a paucity of studies on high-quality responsive NIR-II FL molecules. Herein we report a novel activated NIR-II FL molecule, 4,7-bis­(5-(4-(diphenylamine)­phenyl)-2-thiophene) [1,2,5]­selenadiazolo­[3,4-f]­benzo­[c]­[1,2,5]­thiadiazole (SeTT), which exhibits fast and specific responsive capability to hypochlorous acid (HClO). To obtain the NIR-II ratiometric nanoprobe, SeTT was encapsulated on the surface of Er3+-doped down-conversion nanoparticles (DCNP), achieving the DCNP@SeTT nanoprobe. With a single 980 nm laser excitation, the ratiometric FL signal of SeTT at 1150 nm and DCNP at 1550 nm (I 1150 nm/I 1550 nm) was linearly correlated with the concentration of HClO with a detection limit of 0.4 μM. The ratiometric nanoprobe was successfully investigated for variations in HClO concentration in the tumor progression, visualization of anatomical structures of the peritoneal cavity in the mice model with inflammation, and quantitative detection of the HClO concentration in a rabbit model of osteoarthritis, achieving a fast response and high selectivity for the detection of HClO. The NIR-II-responsive nanoprobe can serve as a promising and effective tool for highly sensitive monitoring and imaging of HClO in living systems.

Radiotherapy remains a major treatment modality for cancer types such as non-small cell lung carcinoma (or NSCLC). To enhance treatment efficacy at a given radiation dose, radiosensitizers are often used during radiotherapy. Herein, we report a nanoparticle agent that can selectively sensitize cancer cells to radiotherapy. Specifically, we nitrosylated maytansinoid DM1 and then loaded the resulting prodrug, DM1-NO, onto poly­(lactide-co-glycolic)-block-poly­(ethylene glycol) (PLGA-b-PEG) nanoparticles. The toxicity of DM1 is suppressed by nanoparticle encapsulation and nitrosylation, allowing the drug to be delivered to tumors through the enhanced permeability and retention effect. Under irradiation to tumors, the oxidative stress is elevated, leading to the cleavage of the S–N bond and the release of DM1 and nitric oxide (NO). DM1 inhibits microtubule polymerization and enriches cells at the G2/M phase, which is more radiosensitive. NO under irradiation forms highly toxic radicals such as peroxynitrites, which also contribute to tumor suppression. The two components work synergistically to enhance radiotherapy outcomes, which was confirmed in vitro by clonogenic assays and in vivo with H1299 tumor-bearing mice. Our studies suggest the great promise of DM1-NO PLGA nanoparticles in enhancing radiotherapy against NSCLC and potentially other tumor types.

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In the treatment of type 2 diabetes mellitus, it is very important to develop therapeutics with prolonged circulation half-life. Exendin-4 is a glucagon like peptide-1 receptor (GLP-1R) agonist that has been modified in different ways for imaging insulinoma and for treating type-2 diabetes. In this work, we synthesized a maleimide derivative of truncated Evans blue dye (MEB-C3-Mal) to conjugate with (Cys40)exendin-4 to obtain a highly stable MEB-C3-(Cys40)exendin-4 (denoted as Abextide II). Through in situ binding with endogenous albumin, Abextide II lowers blood glucose level and prolongs the hypoglycemic effect in a type 2 diabetes mouse model more than the FDA approved Albiglutide.

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Bioimaging guided photothermal therapy possesses great promise for lesion diagnosis and effective treatment. However, distinguishing lesion from normal tissues for precise cancer therapy remains a great challenge. Herein, a stimulation‐responsive assembled Ag2S vesicle (Ag2S Ve) is proposed by self‐assembly of Ag2S quantum dots (QDs) coated with pH‐sensitive copolymer thiolated polystyrene‐co‐poly(4‐vinylpyridine). The Ag2S Ve shows significant absorption enhancement in the near‐infrared (NIR) region and strong fluorescence inhibition in the second near infrared (NIR‐II) region. Triggered by the acidic environment, the release of Ag2S QDs promptly mediates the quenched NIR‐II fluorescence from “off” to “on.” In vivo studies reveal that the theranostic Ag2S Ve can be specifically activated in acidic tumor tissues, whereas it exhibits nonfunctional in normal tissues. Larger sizes endow vesicles a higher tumor accumulation efficiency and controllable disassembly shows illuminating characteristics toward lesion tissues, which provides an innovative therapeutic strategy for activated NIR‐II fluorescence imaging guided cancer therapy.