Folic acid-mediated hollow Mn 3 O 4 nanocomposites for in vivo MRI/FLI monitoring the metastasis of gastric cancer.

BACKGROUND: Metastasis is one of the main factors leading to the high mortality rate of gastric cancer. The current monitoring methods are not able to accurately monitor gastric cancer metastasis. METHODS: In this paper, we constructed a new type of hollow Mn 3 O 4 nanocomposites, Mn 3 O 4 @HMSN-Cy7.5-FA, which had a size distribution of approximately 100 nm and showed good stability in different liquid environments. The in vitro magnetic resonance imaging (MRI) results show that the nanocomposite has good response effects to the acidic microenvironment of tumors. The acidic environment can significantly enhance the contrast of T 1 -weighted MRI. The cellular uptake and endocytosis results show that the nanocomposite has good targeting capabilities and exhibits good biosafety, both in vivo and in vitro. In a gastric cancer nude mouse orthotopic metastatic tumor model, with bioluminescence imaging's tumor location information, we realized in vivo MRI/fluorescence imaging (FLI) guided precise monitoring of the gastric cancer orthotopic and metastatic tumors with this nanocomposite. RESULTS: This report demonstrates that Mn 3 O 4 @HMSN-Cy7.5-FA nanocomposites is a promising nano-diagnostic platform for the precision diagnosis and therapy of gastric cancer metastasis in the future. CONCLUSIONS: In vivo MRI/FLI imaging results show that the nanocomposites can achieve accurate monitoring of gastric cancer tumors in situ and metastases. BLI's tumor location information further supports the good accuracy of MRI/FLI dual-modality imaging. The above results show that the MHCF NPs can serve as a good nano-diagnostic platform for precise in vivo monitoring of tumor metastasis. This nanocomposite provides more possibilities for the diagnosis and therapy of gastric cancer metastases.

Injectable temperature-sensitive hydrogel facilitating endoscopic submucosal dissection.

Purpose: Early gastrointestinal tumors can be removed by endoscopic procedures. Endoscopic mucosal dissection (ESD) requires submucosal fluid injection to provide mucosal elevation and prevent intraoperative perforation. However, the clinically applied normal saline mucosal elevation height is low for a short time, which often requires multiple intraoperative injections that increase the inconvenience and procedure time. In addition, recently researched submucosal injection materials (SIM) suffer from complex preparation, poor economy, and poor biocompatibility. Therefore, there is an urgent need for a new type of SIM that can provide long, safe and effective mucosal elevation in support of the endoscopic procedures. Methods: The FS hydrogel is based on polyethylene-polypropylene glycol (F-127) mixed with sodium alginate (SA). The different physicochemical properties of FS hydrogels were characterized through various experiments. Afterward, various biosafety assessments were carried out. Finally, the performance of FS hydrogels was evaluated by in vitro submucosal injection and in vivo swine ESD. Results: The experimental results show that the FS hydrogel is liquid at room temperature, making it easy to inject, and when injected under the mucosa, it undergoes temperature-induced cross-linking, transforming from a liquid to a solid state to provide long-lasting mucosal augmentation. At the same time, the FS hydrogel exhibits controllable gelation, stability, and biocompatibility. The results of in vitro submucosal injections and in vivo ESD procedures showed that FS achieves high mucosal augmentation and provides good submucosal cushioning in the long term. Conclusion: In summary, the F-127/SA hydrogel is simple to synthesize, cost-effective, safe, easy to store, and able to assist ESD well from the perspective of practical clinical problems, indicating that the FS hydrogel can be an ideal potent submucosal injection substitution.

Rational design of NIR-II molecule-engineered nanoplatform for preoperative downstaging and imaging-guided surgery of orthotopic hepatic tumor.

Orthotopic advanced hepatic tumor resection without precise location and preoperative downstaging may cause clinical postoperative recurrence and metastasis. Early accurate monitoring and tumor size reduction based on the multifunctional diagnostic-therapeutic integration platform could improve real-time imaging-guided resection efficacy. Here, a Near-Infrared II/Photoacoustic Imaging/Magnetic Resonance Imaging (NIR-II/PAI/MRI) organic nanoplatform IRFEP-FA-DOTA-Gd (IFDG) is developed for integrated diagnosis and treatment of orthotopic hepatic tumor. The IFDG is designed rationally based on the core "S-D-A-D-S" NIR-II probe IRFEP modified with folic acid (FA) for active tumor targeting and Gd-DOTA agent for MR imaging. The IFDG exhibits several advantages, including efficient tumor tissue accumulation, good tumor margin imaging effect, and excellent photothermal conversion effect. Therefore, the IFDG could realize accurate long-term monitoring and photothermal therapy non-invasively of the hepatic tumor to reduce its size. Next, the complete resection of the hepatic tumor in situ lesions could be realized by the intraoperative real-time NIR-II imaging guidance. Notably, the preoperative downstaging strategy is confirmed to lower the postoperative recurrence rate of the liver cancer patients under middle and advanced stage effectively with fewer side effects. Overall, the designed nanoplatform demonstrates great potential as a diagnostic-therapeutic integration platform for precise imaging-guided surgical navigation of orthotopic hepatic tumors with a low recurrence rate after surgery, providing a paradigm for diagnosing and treating the advanced tumors in the future clinical translation application.

Indocyanine green-based fluorescence imaging improved by deep learning.

Intraoperative identification of malignancies using indocyanine green (ICG)-based fluorescence imaging could provide real-time guidance for surgeons. Existing ICG-based fluorescence imaging mostly operates in the near-infrared (NIR)-I (700-1000 nm) or the NIR-IIa' windows (1000-1300 nm), which is not optimal in terms of spatial resolution and contrast as their light scattering is higher than the NIR-IIb window (1500-1700 nm). It is highly desired to achieve ICG-based fluorescence imaging in the NIR-IIb window, but it is hindered by its ultra-low NIR-IIb emission tail of ICG. Herein, we employ a generative adversarial network to generate NIR-IIb ICG images directly from the acquired NIR-I ICG images. This approach was investigated by in vivo imaging of sub-surface vascular, intestine structure, and tumors, and their results demonstrated significant improvement in spatial resolution and contrast for ICG-based fluorescence imaging. It is potential for deep learning to improve ICG-based fluorescence imaging in clinical diagnostics and image-guided surgery in clinics.

Cobalt Ferrite-Gossypol Coordination Nanoagents with High Photothermal Conversion Efficiency Sensitizing Chemotherapy against Bcl-2 to Induce Tumor Apoptosis.

Gossypol is a chemotherapeutic drug that can inhibit the anti-apoptotic protein Bcl-2, but the existing gossypol-related nanocarriers cannot well solve the problem of chemotherapy resistance. Based on the observation that gossypol becomes black upon Fe3+ coordination, it is hypothesized that encasing gossypol in glyceryl monooleate (GMO) and making it coordinate cobalt ferrite will not only improve its photothermal conversion efficiency (PCE) but also help it enter tumor cells. As the drug loading content and drug encapsulation efficiency of gossypol are 10.67% (w/w) and 96.20%, the PCE of cobalt ferrite rises from 14.71% to 36.00%. The synergistic therapeutic effect finally induces tumor apoptosis with a tumor inhibition rate of 96.56%, which is 2.99 and 1.47 times higher than chemotherapy or photothermal therapy (PTT) alone. PTT generated by the GMO nanocarriers under the irradiation of 808 nm laser can weaken tumor hypoxia, thereby assisting gossypol to inhibit Bcl-2. In addition, the efficacy of nanocarriers is also evaluated through T2 -weighted magnetic resonance imaging. Observations of gossypol-induced apoptosis in tissue slices provide definitive proof of chemotherapy sensitization, indicating that such coordination nanocarriers can be used as an effective preclinical agent to enhance chemotherapy.

Cone-beam X-ray luminescence computed tomography based on MLEM with adaptive FISTA initial image.

BACKGROUND AND OBJECTIVE: As an emerging dual-mode optical molecular imaging, cone-beam X-ray luminescence computed tomography (CB-XLCT) has shown potential in early tumor diagnosis and other applications with increased depth and little autofluorescence. However, due to the low transfer efficiency of PNPs to convert X-ray energy to visible or near-infrared (NIR) light and X-ray dose limitation, the signal to noise ratio of projections is quite low, making the quality of CB-XLCT relatively poor. METHODS: To improve the reconstruction quality of low-counts CB-XLCT imaging, an adaptive reconstruction algorithm (named ADFISTA-MLEM) based on the maximum likelihood expectation estimation (MLEM) framework is proposed for CB-XLCT reconstruction from Poisson distributed projections. In the proposed framework, the image reconstructed by fast iterative shrinkage-thresholding algorithm (FISTA) is used as the initial image for MLEM iterations to improve reconstruction accuracy, in which both the projection noise model and the sparsity constraint of the image could be considered. For relative quantitative imaging, a specific normalization is applied to the projection data and system matrix. To determine the hyperparameter of FISTA, which may be different for different projections, an adaptive strategy (ADFISTA) is then designed for adaptive update of the hyperparameter with reconstructed image in each iteration. RESULTS AND CONCLUSIONS: Results from numerical simulations and phantom experiments indicate that the proposed framework can obtain superior reconstruction accuracy in terms of contrast to noise ratio and shape similarity. In addition, high intensity-concentration linearity between different probe targets indicates its potential for quantitative CB-XLCT imaging.

Application of radiomics in precision prediction of diagnosis and treatment of gastric cancer.

Gastric cancer is one of the most common malignant tumors. Although some progress has been made in chemotherapy and surgery, it is still one of the highest mortalities in the world. Therefore, early detection, diagnosis and treatment are very important to improve the prognosis of patients. In recent years, with the proposal of the concept of radiomics, it has been gradually applied to histopathological grading, differential diagnosis, therapeutic efficacy and prognosis evaluation of gastric cancer, whose advantage is to comprehensively quantify the tumor phenotype using a large number of quantitative image features, so as to predict and diagnose the lesion area of gastric cancer early. The purpose of this review is to evaluate the research status and progress of radiomics in gastric cancer, and reviewed the workflow and clinical application of radiomics. The 27 original studies on the application of radiomics in gastric cancer were included from web of science database search results from 2017 to 2021, the number of patients included ranged from 30 to 1680, and the models used were based on the combination of radiomics signature and clinical factors. Most of these studies showed positive results, the median radiomics quality score (RQS) for all studies was 36.1%, and the development prospect and challenges of radiomics development were prospected. In general, radiomics has great potential in improving the early prediction and diagnosis of gastric cancer, and provides an unprecedented opportunity for clinical practice to improve the decision support of gastric cancer treatment at a low cost.

Tumor microenvironment responsive Mn3O4 nanoplatform for in vivo real-time monitoring of drug resistance and photothermal/chemodynamic synergistic therapy of gastric cancer.

BACKGROUND: Postoperative chemotherapy for gastric cancer often causes multidrug resistance (MDR), which has serious consequences for therapeutic effects. Individualized treatment based on accurate monitoring of MDR will greatly improve patient survival. RESULTS: In this article, a self-enhanced Mn3O4 nanoplatform (MPG NPs) was established, which can react with glutathione to produce Mn2+ to enhance T1-weighted magnetic resonance imaging (MRI) and mediate in vivo real-time MDR monitoring. In vitro MRI results showed that MRI signals could be enhanced in the presence of hydrogen peroxide and glutathione and at acidic pH. In vivo MRI results indicated that MPG NPs could specifically target MDR cells, thereby realizing real-time monitoring of MDR in gastric cancer. Furthermore, MPG NPs have good chemodynamic activity, which can convert the endogenous hydrogen peroxide of tumor cells into highly toxic hydroxyl radical through Fenton-like reaction at acidic pH to play the role of chemodynamic therapy. In addition, Mn3O4 can significantly enhance the chemodynamic therapy effect because of its good photothermal conversion effect. Furthermore, in situ photothermal/chemodynamic synergistic therapy obtained remarkable results, the tumors of the mice in the synergistic therapy group gradually became smaller or even disappeared. CONCLUSIONS: MPG NPs have good biocompatibility, providing a good nanoplatform for real-time monitoring and precise diagnosis and treatment of MDR in gastric cancer.

DNA Origami-Anthraquinone Hybrid Nanostructures for In Vivo Quantitative Monitoring of the Progression of Tumor Hypoxia Affected by Chemotherapy.

Hypoxia is a well-known feature of malignant solid tumors. To explain the misinterpretation of tumor hypoxia variation during chemotherapy, we developed a DNA origami-based theranostic nanoplatform with an intercalated anticancer anthraquinone as both the chemotherapeutic drug and the photoacoustic contrast agent. The size distribution of the DNA origami nanostructure is 44.5 ± 2.3 nm, whereas the encapsulation efficiency of the drug is 90.7 ± 1.0%, and the drug loading content is 92.2 ± 0.1%. The controlled cumulative release rates were measured in vitro, showing an acidic environment induced rapid drug release. The values of free energy of binding between the drugs and the DNA double helix were calculated through molecular simulations. The cell viability assay was used to characterize cytotoxicity, and fluorescence confocal cell imaging illustrates the biodistribution of the probe in vitro. Photoacoustic and fluorescence imaging were used to indicate drug delivery, release, and biodistribution to predict the drug's chemotherapeutic effect in vivo, whereas the photoacoustic signals were compared with those of deoxygenated/oxygenated hemoglobin to represent the tissue hypoxia/normoxia maps during the chemotherapeutic process and indicate alleviated tumor hypoxia. Staining of tissue sections taken from organs and tumors was used to verify the results of photoacoustic imaging. Our results suggest that photoacoustic imaging can visualize this DNA origami-based theranostic nanoplatform and reveal the mechanisms of chemotherapy on tumor hypoxia.

Britanin Exhibits Potential Inhibitory Activity on Human Prostate Cancer Cell Lines Through PI3K/Akt/NF-κB Signaling Pathways.

Britanin, a natural pseudoguaiacane sesquiterpene lactone, has significant antioxidant and anti-inflammatory activity, but little is known about its tumor inhibitory activity and the underlying mechanism. Here, we demonstrated in vitro and in vivo that britanin inhibited the growth of human prostate cancer cell lines (PC-3, PC-3-LUC, and DU-145). Through in vitro study, the results showed that britanin significantly decreased cell proliferation, migration, and motility. The moderate toxicity of britanin was determined with an acute toxicity study. A luciferase-labeled animal tumor xenograft model and bioluminescence imaging were applied, combining with biological validation for assessing the tumor progression. In vivo results demonstrated that britanin inhibited the growth of PC-3-LUC. The interleukin-2 level in mice was upregulated by britanin, which indicated that britanin induced antitumor immune activation. In addition, britanin downregulated the expression of nuclear factor (NF)-κB p105/p50, pp65, IκBα, pIκBα, phosphoinositide 3-kinase, pPI3k, Akt (protein kinase B, PKB), and pAkt proteins and upregulated expression of Bax. We discovered that britanin inhibits the growth of prostate cancer cells both in vitro and in vivo by regulating PI3K/Akt/NF-κB-related proteins and activating immunity. These findings shed light on the development of britanin as a promising agent for prostate cancer therapy.

Kinetic modeling and analysis of dynamic bioluminescence imaging of substrates administered by intraperitoneal injection.

BACKGROUND: Bioluminescence imaging (BLI) has been found to have diverse applications in the life sciences and medical research due to its ease of use and high sensitivity. From kinetics analysis, dynamic imaging studies have significant advantages for diagnosis when compared to traditional static imaging studies. This work focuses on modeling and quantitatively analyzing the dynamic data produced from the intraperitoneal (IP) injection of D-luciferin in longitudinal BLI, aiming to provide a powerful tool for monitoring the growth of tumors. METHODS: We constructed a three-compartment pharmacokinetic (PK) model and employed the standard Michaelis-Menten (M-M) kinetics to investigate the dynamic BLI data produced from the IP injection of D-luciferin. The 3 compartments were the plasma compartment, the non-specific compartment, and the specific compartment. The validity of this PK model was tested by the dynamic BLI data of MKN28M-luc xenograft mice, along with the published longitudinal dynamic BLI data of B16F10-luc xenograft mice. RESULTS: The R-squares between the simulated lines and the measurement were 1 and 0.99, respectively, for the mice data and the published data. In addition, the 2 kinetic macroparameters obtained reflected the rate of tumor growth in vivo. In particular, the values of macroparameters A showed a significant dependence on tumor surface area. CONCLUSIONS: The proposed PK model may be an effective tool for use in drug development programs and for monitoring the response of tumors to treatment.

The Antitumor Effects of Britanin on Hepatocellular Carcinoma Cells and its Real-Time Evaluation by In Vivo Bioluminescence Imaging.

BACKGROUND: Hepatocellular carcinoma is cancer with many new cases and the highest mortality rate. Chemotherapy is the most commonly used method for the clinical treatment of hepatocellular carcinoma. Natural products have become clinically important chemotherapeutic drugs due to their great potential for pharmacological development. Many sesquiterpene lactone compounds have been proven to have antitumor effects on hepatocellular carcinoma. OBJECTIVE: Britanin is a sesquiterpene lactone compound that can be considered for the treatment of hepatocellular carcinoma. The present study aimed to investigate the antitumor effect of britanin. METHODS: BEL 7402 and HepG2 cells were used to study the cytotoxicity and antitumor effects of britanin. Preliminary studies on the nuclear factor kappa B pathway were conducted by western blot analysis. A BEL 7402-luc subcutaneous tumor model was established for the in vivo antitumor studies of britanin. In vivo bioluminescence imaging was conducted to monitor changes in tumor size. RESULTS: The results of the cytotoxicity analysis showed that the IC50 values for britanin in BEL 7402 and HepG2 cells were 2.702µM and 6.006µM, respectively. The results of the colony formation demonstrated that the number of cells in a colony was reduced significantly after britanin treatment. And the results of transwell migration assays showed that the migration ability of tumor cells was significantly weakened after treatment with britanin. Tumor size measurements and staining results showed that tumor size was inhibited after britanin treatment. The western blot analysis results showed the inhibition of p65 protein expression and reduced the ratio of Bcl-2/Bax after treatment. CONCLUSION: A series of in vitro and in vivo experiments demonstrated that britanin had good antitumor effects and provided an option for hepatocellular carcinoma treatment.

In vivo antitumour activity of Britanin against gastric cancer through nuclear factor-κB-mediated immune response.

OBJECTIVES: Britanin was explored for the antitumour effect on gastric cancer, which is a sesquiterpene lactone (SL) extracted from Inula japonica. METHODS: In the present study, cell viability assays were performed to evaluate the antiproliferation effect of Britanin on gastric cancer cells. Tumour development in BGC-823 cell-bearing nude mice was monitored in real-time after Britanin treatment via a bioluminescent imaging method. Western blotting analysis and enzyme-linked immunosorbent assays detected proteins associated with the nuclear factor (NF)-κB signalling pathway. KEY FINDINGS: Britanin can suppress the proliferation of gastric cancer cells in vitro and the growth of tumours in vivo. In the treatment group, decreased levels of p65 and phosphorylated (p)-p65 were observed. This indicated that NF-κB plays an important role in the antitumour effect of Britanin. Furthermore, considering the additional role of NF-κB in the immune system, the levels of the downstream molecules interleukin (IL)-2 and the cytokine IL-10 were subsequently determined in vivo. An increase in the IL-2 level and a decrease in the IL-10 level indicated that Britanin elicited an enhanced immune response. CONCLUSIONS: Britanin may be a promising candidate for gastric cancer chemotherapy, and its anticancer effect likely depends on an NF-κB-mediated immune response.

Manganese Oxide Nanoparticles As MRI Contrast Agents In Tumor Multimodal Imaging And Therapy.

Contrast agents (CAs) play a crucial role in high-quality magnetic resonance imaging (MRI) applications. At present, as a result of the Gd-based CAs which are associated with renal fibrosis as well as the inherent dark imaging characteristics of superparamagnetic iron oxide nanoparticles, Mn-based CAs which have a good biocompatibility and bright images are considered ideal for MRI. In addition, manganese oxide nanoparticles (MONs, such as MnO, MnO2, Mn3O4, and MnOx) have attracted attention as T1-weighted magnetic resonance CAs due to the short circulation time of Mn(II) ion chelate and the size-controlled circulation time of colloidal nanoparticles. In this review, recent advances in the use of MONs as MRI contrast agents for tumor detection and diagnosis are reported, as are the advances in in vivo toxicity, distribution and tumor microenvironment-responsive enhanced tumor chemotherapy and radiotherapy as well as photothermal and photodynamic therapies.

A photo-triggered conjugation approach for attaching RGD ligands to biodegradable mesoporous silica nanoparticles for the tumor fluorescent imaging.

Fluorescent probes conjugated to peptide or antibody directing groups, which exhibit high signal to background ratios, have been widely used to image tumors and monitor their growth. A photo-triggered cycloaddition reaction between the arginine-glycine-aspartic acid -N-ɛ-acryllysine (RGD-Acrk) peptides and the tetrazole compounds bound to the surface of biodegradable mesoporous silica nanoparticles (bMSN) has been used to construct a fluorescent nanoprobe (bMSN@T2-RGD-Acrk), which showed fluorescent emission at 550 nm and could selectively image the 4T1 cells and breast cancer. This means that the bMSN@T2-RGD-Acrk nanoprobe made by photo-triggered conjugation approach is a promising fluorescent imaging agent for visualizing tumors. Thus, the photo-triggered one-spot reaction can give a stable crosslinker in a biocompatible manner for bioconjugation with nanoparticles and produce a fluorescent group that is suitable for imaging in vivo.

Novel vinyl-modified RGD conjugated silica nanoparticles based on photo click chemistry for in vivo prostate cancer targeted fluorescence imaging.

Molecular imaging is a powerful tool for non-invasive visualization of tumors that plays an important role in their diagnosis and treatment. The specificity of molecular imaging probes for cancer cells is important for accurate tumor visualization, with antibody and polypeptide nanoprobe conjugates having often been used as targeting agents for tumor detection. However, many traditional chemical conjugation methods employ complex conjugation reactions that result in poor efficiency and poor bioactivity. Herein, we describe the use of photo click methodology for the rapid synthesis of nanoprobes comprised of silica nanoparticles functionalized with RGD targeting units (SiO2@T1-RGDk NPs) (∼80 nm) for in vivo prostate cancer fluorescent imaging applications. These SiO2@T1-RGDk NPs exhibit a maximum absorption wavelength of 380 nm in their UV absorption spectra with a maximum fluorescence emission wavelength of 550 nm. Confocal immunofluorescent imaging reveal that SiO2@T1-RGDk NPs exhibit excellent targeting ability for visualizing cancer cells, with in vivo fluorescence imaging intensity in a subcutaneous tumor model of prostate cancer reaching a maxima after 4 h. Biosafety assessments showed that SiO2@T1-RGDk NPs demonstrate no obvious toxicity in mice, thus demonstrated that these novel NPs may prove to be promising fluorescent imaging agents for the accurate detection and treatment of tumors.

Intravenous Administration-Oriented Pharmacokinetic Model for Dynamic Bioluminescence Imaging.

OBJECTIVE: In vivo bioluminescence imaging (BLI) is a promising tool for monitoring the growth and metastasis of tumors. However, quantitative BLI research based on intravenous (IV) injection is limited, which greatly restricts its further application. To address this problem, we designed a pharmacokinetic (PK) model which is suitable for applying on IV administration of small amounts of D-Luciferin. METHODS: After three weeks of postimplantation, mkn28-luc xenografted mice were subjected to 40-min dynamic BLI immediately following D-Luciferin intravenous injection on days 1, 3, 5, 7, and 9. Furthermore, the PK model was applied on dynamic BLI data to obtain the sum of kinetic rate constants (SKRC). RESULTS: Results showed that the SKRC values decreased rapidly with the growth of the tumor. There was a statistical difference between the SKRC values measured at different time points, while the time point of luminous intensity peak was unaffected by the growth of the tumor. CONCLUSION: In short, our results imply that dynamic BLI combined with our PK model can predict tumor growth earlier and with higher sensitivity compared to the conventional method, which is crucial for improving drug evaluation efficacy. In addition, the dynamic BLI may provide a valuable reference for the noninvasive acquiring arterial input function, which may also provide a new application prospect for hybrid PET-optical imaging.

Hypoxia-activated prodrugs and redox-responsive nanocarriers.

Hypoxia is one of the marked features of malignant tumors, which is associated with several adaptation changes in the microenvironment of tumor cells. Therefore, targeting tumor hypoxia is a research hotspot for cancer therapy. In this review, we summarize the developing chemotherapeutic drugs for targeting hypoxia, including quinones, nitroaromatic/nitroimidazole, N-oxides, and transition metal complexes. In addition, redox-responsive bonds, such as nitroimidazole groups, azogroups, and disulfide bonds, are frequently used in drug delivery systems for targeting the redox environment of tumors. Both hypoxia-activated prodrugs and redox-responsive drug delivery nanocarriers have significant effects on targeting tumor hypoxia for cancer therapy. Hypoxia-activated prodrugs are commonly used in clinical trials with favorable prospects, while redox-responsive nanocarriers are currently at the experimental stage.

Intrinsically Zirconium-89-Labeled Manganese Oxide Nanoparticles for In Vivo Dual-Modality Positron Emission Tomography and Magnetic Resonance Imaging.

Manganese-based nanoparticles (NPs) have recently attracted much attention in the field of biomedical imaging due to their impressive enhanced T1 contrast ability. Although the reported manganese-based NPs have exhibited good imaging capabilities as contrast agents, it is still urgent to develop novel multifunctional manganese-based imaging probes for future biomedical imaging, especially PET/MRI probes. Herein, we present chelator-free zirconium-89 (89Zr, t1/2: 78.4 h) labeling of manganese oxide NPs (Mn3O4@PEG) with ∼78% labeling yield and good stability. Serial positron emission tomography (PET) and magnetic resonance imaging (MRI) studies non-invasively assessed the biodistribution patterns of the NPs and the feasibility of in vivo dual-modality imaging and lymph-node mapping. Since Mn3O4 NPs exhibited desirable properties for enhanced T1 imaging and the simplicity of chelator-free radiolabeling, [89Zr]Mn3O4@PEG NPs offer a novel, simple, safe and accurate nanoplatforms for future precise cancer imaging and diagnosis.

In vivo near infrared fluorescence imaging and dynamic quantification of pancreatic metastatic tumors using folic acid conjugated biodegradable mesoporous silica nanoparticles.

Cancer metastasis is one of the biggest challenges in cancer treatments since it increases the likelihood that a patient will die from the disease. Therefore, the availability of techniques for the early detection and quantification of tumors is very important. We have prepared cyanine 7.5 NHS ester (Cy7.5) and folic acid (FA) conjugated biodegradable mesoporous silica nanoparticles (bMSN@Cy7.5-FA NPs) (~100 nm) for visualizing tumors in vivo. The fluorescence spectra revealed that the emission peak of bMSN@Cy7.5-FA NPs had a red-shift of 1 nm. Confocal immunofluorescent images showed that bMSN@Cy7.5-FA NPs had an excellent targeting ability for visualizing cancer cells. In vivo fluorescence imaging has been conducted using an orthotopic model for pancreatic cancer within 48 h, and the fluorescence intensity reached a maximum at a post injection time-point of 12 h, which demonstrated that the use of bMSN@Cy7.5-FA NPs provides an excellent imaging platform for tumor precision therapy in mice.