Fibronectin-targeting and metalloproteinase-activatable smart imaging probe for fluorescence imaging and image-guided surgery of breast cancer.

Residual lesions in the tumor bed have been a challenge for conventional white-light breast-conserving surgery. Meanwhile, lung micro-metastasis also requires improved detection methods. Intraoperative accurate identification and elimination of microscopic cancer can improve surgery prognosis. In this study, a smart fibronectin-targeting and metalloproteinase-activatable imaging probe CREKA-GK8-QC is developed. CREKA-GK8-QC possesses an average diameter of 21.7 ± 2.5 nm, excellent MMP-9 protein responsiveness and no obvious cytotoxicity. In vivo experiments demonstrate that NIR-I fluorescence imaging of CREKA-GK8-QC precisely detects orthotopic breast cancer and micro-metastatic lesions (nearly 1 mm) of lungs with excellent imaging contrast ratio and spatial resolution. More notably, fluorescence image-guided surgery facilitates complete resection and avoids residual lesions in the tumor bed, improving survival outcomes. We envision that our newly developed imaging probe shows superior capacity for specific and sensitive targeted imaging, as well as providing guidance for accurate surgical resection of breast cancer.

Robust ERα-Targeted Near-Infrared Fluorescence Probe for Selective Hydrazine Imaging in Breast Cancer.

Breast cancer is the most common malignancy in women and may become worse when a high concentration of hydrazine is absorbed from the environment or drug metabolite. Therefore, rapid and sensitive detection of hydrazine in vivo is beneficial for people's health. In this work, a novel estrogen receptor α (ERα)-targeted near-infrared fluorescence probe was designed to detect hydrazine levels. The probe showed good ERα affinity and an excellent fluorescence response toward hydrazine. Selectivity experiments demonstrated that the probe had a strong anti-interference ability. Mechanistic studies, including mass spectrometry (MS) and density functional theory (DFT) calculation, indicated that intermolecular charge transfer (ICT) progress was hindered when the probe reacted with hydrazine, resulting in fluorescent quenching. In addition, the probe could selectively bind to MCF-7 breast cancer cells with excellent biocompatibility. The in vivo and ex vivo imaging studies demonstrated that the probe could rapidly visualize hydrazine with high contrast in MCF-7 xenograft tumors. Therefore, this probe can serve as a potential tool to robustly monitor hydrazine levels in vivo.

Yolk-shell shaped Au-Bi2S3heterostructure nanoparticles for controlled drug release and combined tumor therapy.

To fabricate a novel stimuli-responsive system enabling controlled drug release and synergistic therapy, yolk-shell shaped bismuth sulfide modified with Au nanoparticles (Au-Bi2S3) was prepared. The Au-Bi2S3nanomaterial with heterojunction structure exhibited excellent photothermal conversion efficiency and considerable free radicals yield under laser irradiation. The drug delivery capacity was confirmed by co-loading Berberine hydrochloride (BBR) and a phase change material 1-tetradecanol (PCM), which could be responsible for NIR light induced thermal controlled drug release.In vitroinvestigation demonstrated that Au-Bi2S3has cell selectivity, and with the assistance of the properties of Au-Bi2S3, the loaded drug could give full play to their cancer cell inhibition ability. Our work highlights the great potential of this nanoplatform which could deliver and control Berberine hydrochloride release as well as realize the synergistic anti-tumor strategy of photothermal therapy, photodynamic therapy and chemotherapy for tumor therapy.

Integration of TaOx with Bi2S3 for Targeted Multimodality Breast Cancer Theranostics.

Early identification and treatment of breast cancer is very important for breast conserving therapy and to improve the prognosis and survival rates of patients. Multifunctional nanotheranostic agents are of particular importance in the field of precise nanomedicine, since they can augment the visualization and treatment of cancer. We developed a novel Bi2S3 nanoparticle coated with a hyaluronic acid (HA)-modified tantalum oxide (TaOx) nanoshell (Bi2S3@TaOx-HA). The as-prepared core/shell nanoparticles exhibited a high Bi2S3 nanoparticle loading efficiency of (67 wt %). The TaOx nanoshell exhibited excellent biocompatibility and computed tomography imaging capacity, and the Bi2S3 nanoparticles exhibited an excellent photothermal transducing performance and computed tomography (CT) and photoacoustic imaging capacity. As a result of these merits, the Bi2S3@TaOx core-shell nanoparticles can act as a theranostic agent for CT/photoacoustically monitored enhanced photothermal therapy. These findings will evoke new interest in future cancer therapeutic strategies based on biocompatible functional nanomaterials.

Preoperative Examination and Intraoperative Identification of Hepatocellular Carcinoma Using a Targeted Bimodal Imaging Probe.

In clinical imaging modalities, MRI is suitable for preoperative examination. Fluorescence imaging has been proposed to improve the detectability of cancer lesions during the operation. However, the specificity and accuracy of the two imaging modalities is limited. To improve the prognosis and survival rate of the patient suffering from hepatocellular carcinoma (HCC), it is very important to develop a specific probe to achieve early detection and precise resection of HCC. We selected HCC targeting peptide SP94 to conjugate with a NIR dye and Gd chelated DOTA to enhance the specificity of different imaging modalities. MRI and fluorescence imaging were used for preoperative examination of the cancer and detecting the tumor in the operation, respectively. MRI and fluorescence signals significantly increased when HCC occurs and the obtained probe shows high uptake in HCC but negligible uptake in the normal liver tissues. The signal-to-background ratio is higher than 2.23 (MRI) and 2.0 (fluorescence imaging) with noninvasive imaging modalities. After the intraperitoneal cavity was surgically exposed, the signal-to-background ratio is higher than 4.6. By combining the high specificity of our probe with the high sensitivity of fluorescence imaging, the microprimary malignancy and micrometastasis foci (diameter <1 mm) can be easily detected after the intraperitoneal cavity is exposed. These results indicated that our probe is conductive to the early detection and precise resection of the HCC and has the potential to improve the diagnosis and treatment of patients with HCC.

Microwave-Triggered Smart Drug Release from Liposomes Co-encapsulating Doxorubicin and Salt for Local Combined Hyperthermia and Chemotherapy of Cancer.

The microwave and temperature sensitive liposomes were fabricated successfully from 1,2-dipalmityol-sn-glycero-3-phosphocholine (DPPC), cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000 (DSPE-PEG2000) with a molar ratio of 4:1:0.26 by co-encapsulating NaCl and doxorubicin (DOX) through the thin-film hydration method to externally manipulate drug release at a predetermined location in the body at a desired time in the right dosage for combination microwave hyperthermia and chemotherapy of cancer to afford a synergistic therapeutic effect. It was found that the confinement of the high concentration of NaCl ions inside the small size of the liposomes led to a more-rapid temperature elevation than the dissociative ions upon microwave treatment. More than 67.6% doxorubicin was released from the DOX and NaCl co-loaded liposomes (DOX&NaCl@liposomes) upon microwave irradiation for 2 min. After incubation with 2 mg/mL DOX&NaCl@liposomes for 4 h followed by treatment with microwave for 2 min, the inhibition rate of human breast cancer cell MDA-MB-231 was evaluated as 76.1%, much higher than that for NaCl@liposomes (29.8%) and DOX@liposomes (40.2%). The tumor growth inhibition was evaluated to be 73.4% after intravenous injection of DOX&NaCl@liposomes followed by microwave irradiation, much higher than that with only NaCl@liposomes (41.5%) or DOX@liposomes (45.5%) combined with microwave irradiation. Therefore, DOX&NaCl@liposomes could serve as a promising thermochemotherapy nanomedicine for cancer treatment because of its excellent microwave susceptible property and good biocompatibility.

Hyaluronic Acid Modified Tantalum Oxide Nanoparticles Conjugating Doxorubicin for Targeted Cancer Theranostics.

Theranostic tantalum oxide nanoparticles (TaOxNPs) of about 40 nm were successfully developed by conjugating functional molecules including polyethylene glycol (PEG), near-infrared (NIR) fluorescent dye, doxorubicin (DOX), and hyaluronic acid (HA) onto the surface of the nanoparticles (TaOx@Cy7-DOX-PEG-HA NPs) for actively targeting delivery, pH-responsive drug release, and NIR fluorescence/X-ray CT bimodal imaging. The obtained nanoagent exhibits good biocompatibility, high cumulative release rate in the acidic microenvironments, long blood circulation time, and superior tumor-targeting ability. Both in vitro and in vivo experiments show that it can serve as an excellent contrast agent to simultaneously enhance fluorescence imaging and CT imaging greatly. Most importantly, such a nanoagent could enhance the therapeutic efficacy of the tumor greatly and the tumor growth inhibition was evaluated to be 87.5%. In a word, multifunctional TaOx@Cy7-DOX-PEG-HA NPs can serve as a theranostic nanomedicine for fluorescence/X-ray CT bimodal imaging, remote-controlled therapeutics, enabling personalized detection, and treatment of cancer with high efficacy.

Gold nanoshelled liquid perfluorocarbon nanocapsules for combined dual modal ultrasound/CT imaging and photothermal therapy of cancer.

The integration of multimodal contrast-enhanced diagnostic imaging and therapeutic capabilities could utilize imaging guided therapy to plan the treatment strategy based on the diagnostic results and to guide/monitor the therapeutic procedures. Herein, gold nanoshelled perfluorooctylbromide (PFOB) nanocapsules with PEGylation (PGsP NCs) are constructed by oil-in-water emulsion method to form polymeric PFOB nanocapsules, followed by the formation of PEGylated gold nanoshell on the surface. PGsP NCs could not only provide excellent contrast enhancement for dual modal ultrasound and CT imaging in vitro and in vivo, but also serve as efficient photoabsorbers for photothermal ablation of tumors on xenografted nude mouse model. To our best knowledge, this is the first report of gold nanoshell serving as both CT contrast agents and photoabsorbers for photothermal therapy. The novel multifunctional nanomedicine would be of great value to offer more comprehensive diagnostic information to guide more accurate and effective cancer therapy.

Multifunctional ultrasound contrast agents for imaging guided photothermal therapy.

Among all the imaging techniques, ultrasound imaging has a unique advantage due to its features of real-time, low cost, high safety, and portability. Ultrasound contrast agents (UCAs) have been widely used to enhance ultrasonic signals. One of the most exciting features of UCAs for use in biomedicine is the possibility of easily putting new combinations of functional molecules into microbubbles (MBs), which are the most routinely used UCAs. Various therapeutic agents and medical nanoparticles (quantum dots, gold, Fe3O4, etc.) can be loaded into ultrasound-responsive MBs. Hence, UCAs can be developed as multifunctional agents that integrate capabilities for early detection and diagnosis and for imaging guided therapy of various diseases. The current review will focus on such state-of-the-art UCA platforms that have been exploited for multimodal imaging and for imaging guided photothermal therapy.

Magnetic Prussian blue nanoparticles for targeted photothermal therapy under magnetic resonance imaging guidance.

This paper reported a core-shell nanotheranostic agent by growing Prussian blue (PB) nanoshells of 3-6 nm around superparamagnetic Fe3O4 nanocores for targeted photothermal therapy of cancer under magnetic resonance imaging (MRI) guidance. Both in vitro and in vivo experiments proved that the Fe3O4@PB core-shell nanoparticles showed significant contrast enhancement for T2-weighted MRI with the relaxivity value of 58.9 mM(-1)·s(-1). Simultaneously, the composite nanoparticles exhibited a high photothermal effect under irradiation of a near-infrared laser due to the strong absorption of PB nanoshells, which led to more than 80% death of HeLa cells with only 0.016 mg·mL(-1) of the nanoparticles with the aid of the magnetic targeting effect. Using tumor-bearing nude mice as the model, the near-infrared laser light ablated the tumor effectively in the presence of the Fe3O4@PB nanoparticles and the tumor growth inhibition was evaluated to be 87.2%. Capabilities of MRI, magnetic targeting, and photothermal therapy were thus integrated into a single agent to allow efficient MRI-guided targeted photothermal therapy. Most importantly, both PB and Fe3O4 nanoparticles were already clinically approved drugs, so the Fe3O4@PB nanoparticles as a theranostic nanomedicine would be particularly promising for clinical applications in the human body due to the reliable biosafety.

Doping hydroxylated cationic lipid into PEGylated cerasome boosts in vivo siRNA transfection efficacy.

The therapeutic application of small interfering RNA (siRNA) requires safe nanocarriers for specific and efficient delivery in vivo. Herein, PEGylated cationic cerasomes (PCCs) were fabricated by doping a cationic lipid with a hydroxyl group into nanohybrid cerasomes. Multiple properties of PCCs provide a solution to many of the limitations associated with current platforms for the delivery of siRNA. The polyorganosiloxane surface imparts PCCs with higher morphological stability than conventional liposomes. The PEGylation of the cationic cerasome could protect the cerasome nanoparticles from agglomeration and macrophage capture, reduce protein absorption, and consequently prolong the blood circulating time and enhance the siRNA delivery efficiency. In addition, incorporation of the lipid containing a hydroxyl group further facilitates endosome release. Moreover, PCCs were further used to transport siRNA into the cytosol primarily via endocytosis. When applied to systemic administration, PCCs have demonstrated effective delivery into the liver and preferential uptake by hepatocytes in mice, thereby leading to high siRNA gene-silencing activity. All these results show potential therapeutic applications of PCCs-mediated delivery of siRNA for liver diseases.

Glucose-Regulated Protein 78 Targeting ICG and DOX Loaded Hollow Fe3O4 Nanoparticles for Hepatocellular Carcinoma Diagnosis and Therapy.

Purpose: Liver cancer is considered as the third leading cause of cancer-related deaths, with hepatocellular carcinoma (HCC) accounting for approximately 90% of liver cancers. Improving the treatment of HCC is a serious challenge today. The primary objective of this study was to construct SP94-Fe3O4@ICG&DOX nanoparticles and investigate their potential diagnosis and treatment effect benefits on HCC. Methods: Firstly, we synthesized and characterized SP94-Fe3O4@ICG&DOX nanoparticles and confirmed their in vitro release behavior, photothermal and photodynamic performance. Moreover, the in vivo imaging capability was also observed. Finally, the inhibitory effects on Hepa1-6 in vitro and in vivo were observed as well as biosafety. Results: SP94-Fe3O4@ICG&DOX nanoparticles have a size of ~22.1 nm, with an encapsulation efficiency of 45.2% for ICG and 42.7% for DOX, showing excellent in vivo MPI and fluorescence imaging capabilities for precise tumor localization, and synergistic photo-chemotherapy (pH- and thermal-sensitive drug release) against tumors under irradiation. With the assistance of a fluorescence molecular imaging system or MPI scanner, the location and contours of the tumor were clearly visible. Under a constant laser irradiation (808 nm, 0.6 W/cm2) and a set concentration (50 µg/mL), the temperature of the solution could rapidly increase to ~45 °C, which could effectively kill the tumor cells. It could be effectively uptaken by HCC cells and significantly inhibit their proliferation under the laser irradiation (100% inhibition rate for HCC tumors). And most importantly, our nanoparticles exhibited favorable biocompatibility with normal tissues and cells. Conclusion: This versatile agent can serve as an intelligent and promising nanoplatform that integrates multiple accurate diagnoses, precise positioning of cancer tissue, and effective coordination with synergistic tumor photodynamic therapy.

Enhancing enzymatic digestibility of bamboo residues using a combined low severity steam explosion and green liquor-sulfite pretreatment.

In this study, the effect of the green liquor (GL)-sulfite pretreatment on bamboo for enzymatic hydrolysis was investigated. The performance characterization of the pretreated bamboo substrates, including the chemical composition, and the structural characteristics was carried out. The results showed that 91.3% of lignin removal was achieved when the sample was treated with a GL loading of 12.0 mL per g-DS at 120 °C for 1 h. After 120 h hydrolysis with 18 FPU per g-cellulose for cellulase and 27 CBU per g-cellulose for glucosidase, the glucose yield increased from 54.6% to 89.6%. The SE-treated bamboo could bind more easily to cellulase than GL-sulfite treated bamboo could. The structural changes on the surface of the samples were characterized by SEM. The results indicated that the surface lignin could be effectively removed during pretreatment, thereby decreasing the enzyme-lignin binding activity.

A SILAC-based accurate quantification of shrimp allergen tropomyosin in complex food matrices using UPLC-MS/MS.

The carryover of trace allergens in complex food matrices poses challenges for detection techniques. Here, we demonstrate an accurate UPLC-MS/MS quantification assay for the shrimp allergen tropomyosin with a full-length isotope-labelled recombinant tropomyosin (TM-I) internal standard in complex food matrices. The TM-I, expressed based on the SILAC technique, exhibited a high isotope labelling ratio (>99%), purity, and alignment with the natural sequence. This method determined the tropomyosin ranging from 0.2 to 100 ng/mL. Mean recoveries ranged from 89 to 116%, with intra- and inter-day RSDs below 12%, for three signature peptides across three types of commercially processed food matrices. The limits of quantitation were 1 µg/g in pop food and sauce, and 10 µg/g in surimi product, respectively. This study supports the use of recombinant full-length isotope-labelled proteins rather than stable-isotope labelling peptides as internal standards to achieve more accurate quantitation of food allergens as the digestion error is corrected.

Biotransformation of carbendazim in cowpea pickling process.

Carbendazim, a systemic fungicide, is one of the most commonly detected pesticides in cowpeas. Pickled cowpea is a fermented vegetable product with unique flavor favored in China. The dissipation and degradation of carbendazim were investigated in the pickled process. The degradation rate constant of carbendazim in pickled cowpeas was 0.9945 and the half-life of the carbendazim was 14.06 ± 0.82 d. Seven transformation products (TPs) were identified in the pickled process. Furthermore, the toxicity of some TPs show more harmful to three aquatic organisms (TP134) and rats (all the identified TPs) than carbendazim. And most of the TPs posed more development toxicity and mutagenicity than carbendazim. 4 out of 7 TPs were discovered in the real pickled cowpea samples. These results shed light on the degradation and biotransformation of the carbendazim in the pickled process, to better understand the potential health risk of pickled food and evaluate the environmental pollution.

Magnetic amino-rich hyper-crosslinked polymers for fat-rich foodstuffs pretreatment in nontargeted analysis of chemical hazards.

Nontargeted analysis for chemical hazards is highly desirable in controlling food safety to ensure human health. As the dominating interference in fat-rich foodstuffs, lipids removal is a great challenge in sample pretreatment. Herein, diverse lipids from both animal and vegetable oils are effectively removed and 565 chemical hazards with various physicochemical properties are used for method validation. These benefits are from the designed magnetic amino-rich hyper-crosslinked core-shell polymeric composites (Fe3O4@poly(MAAM-co-EGDMA)) and the application of an auto extraction system. Among them, the amino groups are the key factors for lipid removal. Theoretical calculations, isothermal titration calorimetry (ITC), and functional monomer replacement demonstrated that the mechanisms to universally capture free fatty acids (FFAs) and triglycerides (TGs) are electrostatic interaction and supplemented by hydrogen bonding. Overall, this work highlights the great application potentials of polymeric adsorbents as sample pretreatment materials for nontargeted analysis in food safety.

Recent advances in HDAC-targeted imaging probes for cancer detection.

Histone Deacetylases (HDACs) are abnormally high expressed in various cancers and play a crucial role in regulating gene expression. While HDAC-targeted inhibitors have been rapidly developed and approved in the last twenty years, noninvasive monitoring and visualizing the expression levels of HDACs in tumor tissues might help to early diagnosis in cancer and predict the response to HDAC-targeted cancer therapy. In this review, we summarize the recent advancements in the development of HDAC-targeted probes and their applications in cancer imaging and image-guided surgery. We also discuss the design strategies, advantages and disadvantages of these probes. We hope that this review will provide guidance for the design of HDAC-targeted imaging probes and clinical applications in future.

A Hepatocellular Carcinoma Targeting Nanostrategy with Hypoxia-Ameliorating and Photothermal Abilities that, Combined with Immunotherapy, Inhibits Metastasis and Recurrence.

Hepatocellular carcinoma (HCC) is a common and highly malignant tumor that is prone to recurrence and metastasis and has no effective treatment. Unsurprisingly, its prognosis is quite poor; early detection methods and effective low-toxicity treatments are urgently needed. To achieve these goals, we designed a multifunctional, U.S. Food and Drug Administration-approved Prussian blue (PB) nanoparticle (NP) with a porous metal organic frame loaded with sorafenib (SF), conjugated with HCC-specific targeting peptide SP94 and the near-infrared dye cyanine (Cy)5.5. These NPs are amenable to multimodal imaging for dynamic monitoring of their biodistribution and tumor-targeting effects. The SP94-PB-SF-Cy5.5 NPs achieved targeted delivery and controlled SF release and exhibited good photothermal effects. In this strategy, photothermal therapy and SF treatment complement each other, reducing the side effects of SF and achieving a therapeutic effect without local tumor recurrence. In addition, the catalase-like ability of the NPs alleviates tumor hypoxia, and their photothermal effects induce immunogenic cell death, leading to the release of tumor-associated antigens. These effects combine to trigger an antitumor immune response; the NPs also displayed promising inhibitory effects on tumor metastasis and recurrence and produced an abscopal effect and long-term immunological memory when combined with antiprogrammed death-ligand 1 (PD-L1) immunotherapy. These safe, multifunctional NPs represent a valuable treatment option for HCC. In addition, this next-generation treatment model may provide some ideas for the management of HCC and other cancers.

Neuroblastoma-targeting triangular gadolinium oxide nanoplates for precise excision of cancer.

Neuroblastoma accounts for 8-10% of malignancies in infants and children. It is urgent to develop an appropriate theranostic agent for effective diagnosis and therapy of neuroblastoma. Herein, we constructed RVG peptide and IRDye800-conjugated bovine serum albumin-coated triangular gadolinium oxide nanoplates (RVG&IRDye800-Gd2O3 TNs) as a targeting MRI agent for the diagnosis of neuroblastoma preoperation and a fluorescence imaging agent for the guidance of the precise excision of the neuroblastoma in surgery. RVG&IRDye800-Gd2O3 TNs have uniform edge length. The RVG&IRDye800-Gd2O3 TNs show remarkably enhanced affinity to both mouse- and human-derived neuroblastoma cells compared with IRDye800-Gd2O3 TNs (3.07-fold and 3.02-fold, respectively). Because of the increased accumulation in tumor cells, RVG&IRDye800-Gd2O3 TNs exhibit signals threefold to fivefold higher than the surrounding normal tissues, which is propitious to the diagnosis of neuroblastoma preoperation and provides real-time visual guidance of the precise excision of the neuroblastoma. Most importantly, with the guidance of the fluorescence imaging agent, the survival rate increased from 0% to 80% 42 days after surgery compared with that in conventional surgery. These findings indicated that the RVG peptide combined with IRDye800-Gd2O3 TNs has the potential to improve the diagnosis and treatment of patients with neuroblastoma. STATEMENT OF SIGNIFICANCE: In this study, we prepared RVG peptide and IRDye800-conjugated bovine serum albumin-coated triangular gadolinium oxide nanoplates (RVG&IRDye800-Gd2O3 TNs) as a targeting MRI agent for the diagnosis of neuroblastoma preoperation and a fluorescence imaging agent for the guidance of the precise excision of the neuroblastoma during surgery. Neuroblastoma was accurately located by MRI imaging, and the tumor margin could be real-time monitored through near-infrared fluorescence imaging. The RVG&IRDye800-Gd2O3 TNs exhibit signals threefold to fivefold higher than those in the surrounding normal tissues, which is propitious to the diagnosis of the neuroblastoma preoperation and provides real-time visual guidance of the precise excision of the neuroblastoma. With the guidance of the fluorescence imaging agent in surgery, the survival rate increased from 0% to 80% 42 days after surgery compared with that in conventional surgery.

Adaptive Gaussian Weighted Laplace Prior Regularization Enables Accurate Morphological Reconstruction in Fluorescence Molecular Tomography.

Fluorescence molecular tomography (FMT), as a powerful imaging technique in preclinical research, can offer the three-dimensional distribution of biomarkers by detecting the fluorescently labelled probe noninvasively. However, because of the light scattering effect and the ill-pose of inverse problem, it is challenging to develop an efficient reconstruction method, which can provide accurate location and morphology of the fluorescence distribution. In this research, we proposed a novel adaptive Gaussian weighted Laplace prior (AGWLP) regularization method, which assumed the variance of fluorescence intensity between any two voxels had a non-linear correlation with their Gaussian distance. It utilized an adaptive Gaussian kernel parameter strategy to achieve accurate morphological reconstructions in FMT. To evaluate the performance of the AGWLP method, we conducted numerical simulation and in vivo experiments. The results were compared with fast iterative shrinkage (FIS) thresholding method, split Bregman-resolved TV (SBRTV) regularization method, and Gaussian weighted Laplace prior (GWLP) regularization method. We validated in vivo imaging results against planar fluorescence images of frozen sections. The results demonstrated that the AGWLP method achieved superior performance in both location and shape recovery of fluorescence distribution. This enabled FMT more suitable and practical for in vivo visualization of biomarkers.