The abnormal expression of tumor-associated proteases and lowered extracellular pH are important signatures strongly associated with cancer invasion, progression, and metastasis. However, their malignant effects were mainly identified using cell and tissue studies. To noninvasively visualize the heterogeneous distribution of these abnormal indicators in vivo and further disclose their collective behaviors, a target-triggered fluorescent nanoprobe composed of a ratiometric pH-sensitive dye, a near-infrared dye (Cy5.5), and biocompatible FeO nanoparticles was constructed. The pH-sensitive dye was linked through a peptide substrate of matrix metalloprotease-9 (MMP-9) with FeO nanoparticles to establish a Förster resonance energy transfer (FRET) system for sensing the pH of the tumor microenvironment. Cy5.5 served as an internal reference for forming a secondary ratiometric fluorescent system together with the activated pH dye to enable the visualization of protease activities in vivo. Extensive imaging studies using a mouse model of human colon cancer revealed that the overexpression of MMP-9 and abnormal microenvironmental pH quantitatively visualized by this dual-ratiometric probe are spatially heterogeneous and synergistically guide the tumor invasion in vivo.

Many challenges for advanced sensitive and noninvasive clinical diagnostic imaging remain unmatched. In particular, the great potential of magnetic nano-probes is intensively discussed to further improve the performance of magnetic resonance imaging (MRI), especially for cancer diagnosis. Based on recent achievements, here the concepts of magnetic nanoparticle-based MRI contrast agents and tumor-specific imaging probes are critically summarized. Advances in their synthesis, biocompatible chemical and biofunctional surface modifications, and current strategies for further developing them into multimodality imaging probes are discussed. In addition, how engineered versus unintended surface coatings such as protein coronas affect the biocompatibility and performance of MRI nano-probes is also considered. To stimulate progress in the field, future strategies and relevant challenges that still need to be resolved in the field conclude this review.

Exogenous FeIII can be used for cancer magnetic resonance (MR) imaging and potentially for cancer treatment by a ferroptosis pathway or photothermal ablation. To achieve this, effective and accurate delivery of FeIII to cancerous sites is critical, requiring a balance of release kinetics of Fe3+ in tumorous and normal tissues. A nanoprobe is described consisting of upconversion luminescence (UCL) nanoparticles as a core and a coordinatively unsaturated FeIII‐containing Fe3+/gallic acid complex as a shell. Owing to the introduction of an unsaturated coordination structure, FeIII in the nanoprobe can be released only in the tumor microenvironment in response to the lightly acidic pH. The multiple UCLs are used for quantitatively visualizing the release of Fe3+ in vivo, whilst the release resultant serves as a photothermal agent. This nanoprobe exhibited ligand‐free tumor targeting ability, activatable MR imaging performance, and efficacious therapeutic effects against tumors in vivo.

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Nanocellulose, a form of nanostructured cellulose, exists as either cellulose nanocrystal (CNC, also called nanocrystalline cellulose or cellulose nanowhisker), cellulose nanofiber (CNF, also referred to as nanofibrillated cellulose), or bacterial nanocellulose (also referred to as nano-structured cellulose produced by bacteria). [1][2][3][4][5][6] In light of its various and outstanding advantages including high mechanical strength, stiffness, low weight, high specific surface area, recyclability, bioavailability, biocompatibility, surface tunable chemistry, and rheological properties, nanocellulose has been increasingly considered for applications in papermaking, coatings, food, nanocomposite formulations and reinforcement, as well as in the innovative biomedical fields, including used as drug delivery carriers, 3D culture, antimicrobial materials, and tissue repair and regeneration areas. [2,[4][5][6][7][8][9][10][11] The nanocellulose production has a high economic impact and the global nanocellulose market will be projected to grow to approximately $730 million by 2023. [11] This stresses the importance of understanding the toxicity of nanocellulose to generate knowledge that will contribute to predict the health effects from exposure, reduce the risk to humans, or design safer nanocellulose materials for biomedical applications.Although nanocellulose is generally regarded as safe based on its biocompatibility as well as biodegradability and the great majority of studies have pointed to the absence of significant cytotoxic effects by a vast diversity of CNC samples from different origins and with diverse properties in many mammalian cell lines, recent studies have been reported that nanocellulose displayed the adverse effects in vitro and in vivo. [11][12][13][14] For example, the CNCs in the 200-300 nm length scales have been shown to induce significant lysosomal damage, NLRP3 inflammasome activation as well as IL-1β production in the human myeloid cell line, THP-1. [15] Also, Yanamala et al. demonstrated that the generation of oxidative stress, cytotoxicity, and proinflammatory by oropharyngeal aspiration of CNCs in mice. [16] The nanocellulose is beneficial for the design of advanced drug Nanocellulose including cellulose nanocrystal (CNC) and cellulose nanofiber (CNF) has attracted much attention due to its exceptional mechanical, chemical, and rheological properties. Although considered biocompatible, recent reports have demonstrated nanocellulose can be hazardous, including serving as drug carriers that accumulate in the liver. However, the nanocellulose effects on liver cells, including Kupffer cells (KCs) and hepatocytes are unclear. Here, the toxicity of nanocellulose with different lengths is compared, including the shorter CNCs (CNC-1, CNC-2, and CNC-3) and longer CNF (CNF-1 and CNF-2), to liver cells. While all CNCs triggered significant cytotoxicity in KCs and only CNC-2 induced toxicity to hepatocytes, CNFs failed to induce significant cytotoxicity due to their minimal cellular uptake. The phag...

Physiological parameters in tumor microenvironments, including hypoxia, low extracellular pH, enzymes, reducing conditions, and so on, are closely associated with the proliferation, angiogenesis, invasion, and metastasis of cancer, and impact the therapeutic administrations. Therefore, monitoring the tumor microenvironment is significant for diagnosing tumors, predicting the invasion potential, evaluating therapeutic efficacy, planning the treatment, and cancer prognostics. Noninvasive molecular imaging technologies combined with novel "smart" nanoparticle-based activatable probes provide a feasible approach to visualize tumor-associated microenvironment factors. This review summarizes recent achievements in the designs of "smart" molecular imaging nanoprobes responding to the tumor microenvironment-related features, and highlights the state of the art in tumor heterogeneity imaging.

Ischemic stroke is one of the major leading causes for long-term disability and mortality. Collateral vessels provide an alternative pathway to protect the brain against ischemic injury after arterial occlusion. Aiming at visualizing the collaterals occurring during acute ischemic stroke, an integrin α β -specific Fe O -Arg-Gly-Asp (RGD) nanoprobe is prepared for magnetic resonance imaging (MRI) of the collaterals. Rat models are constructed by occluding the middle cerebral artery for imaging studies of cerebral ischemia and ischemia-reperfusion on 7.0 Tesla MRI using susceptibility-weighted imaging sequence. To show the binding specificity to the collaterals, the imaging results acquired with the Fe O -RGD nanoprobe and the Fe O mother nanoparticles, respectively, are carefully compared. In addition, an RGD blocking experiment is also carried out to support the excellent binding specificity of the Fe O -RGD nanoprobe. Following the above experiments, cerebral ischemia-reperfusion studies show the collateral dynamics upon reperfusion, which is very important for the prognosis of various revascularization therapies in the clinic. The current study has, for the first time, enabled the direct observation of collaterals in a quasi-real time fashion and further disclosed that the antegrade flow upon reperfusion dominates the blood supply of primary ischemic tissue during the early stage of infarction, which is significantly meaningful for clinical treatment of stroke.

2D boron nitride (BN) and molybdenum disulfide (MoS2) materials are increasingly being used for applications due to novel chemical, electronic, and optical properties. Although generally considered biocompatible, recent data have shown that BN and MoS2 could potentially be hazardous under some biological conditions, for example, during, biodistribution of drug carriers or imaging agents to the liver. However, the effects of these 2D materials on liver cells such as Kupffer cells (KCs), liver sinusoidal endothelial cells, and hepatocytes, are unknown. Here, the toxicity of BN and MoS2, dispersed in Pluronic F87 (designated BN‐PF and MoS2‐PF) is compared with aggregated forms of these materials (BN‐Agg and MoS2‐Agg) in liver cells. MoS2 induces dose‐dependent cytotoxicity in KCs, but not other cell types, while the BN derivatives are non‐toxic. The effect of MoS2 could be ascribed to nanosheet dissolution and the release of hexavalent Mo, capable of inducing mitochondrial reactive oxygen species generation and caspases 3/7‐mediated apoptosis in KUP5 cells. In addition, the phagocytosis of MoS2‐Agg triggers an independent response pathway involving lysosomal damage, NLRP3 inflammasome activation, caspase‐1 activation, IL‐1β, and IL‐18 production. These findings demonstrate the importance of Mo release and the state of dispersion of MoS2 in impacting KC viability.