Application of Nanoparticles in the Diagnosis of Gastrointestinal Diseases: A Complete Future Perspective

Figures & data

Table 1 Commercialized NPs Have Been Explored as Contrast Agents for Molecular Imaging

NP Type	Targets	Imaging Modality	Animal Model	Outcome	Ref.
Quantum dots	Glucose transporter1 (Glut1)	MRI	CRC-bearing mice	Specifically recognizing Glut1 in CRC cells and improving the accuracy of CRC diagnosis and biopsy.	[13]
Superparamagnetic iron oxide NPs (SPIONPs)	Kupffer cells	MRI	Patients with hepatocellular carcinoma (HCC)	Improving the detection of HCC and the capacity to differentiate lesions.	[14]
Silica NPs	CD146	MRI/ Near-infrared fluorescence (NIRF)	MKN45 tumor-bearing nude mice	Allowing for rapid and accurate tumor imaging, with the potential to guide tumor treatment and surgery.	[15]
SPIONPs	Macrophages	MRI/PET/CT	IBD mice	Assessment of inflammatory activity in IBD.	[16]
CuS NPs	αvβ3/ matrix metalloprotease-2 (MMP-2)	MRI/NIRF	Gastric tumor-bearing mice	Accurate identification of gastric tumor.	[17]
Radiotracer-liposome	Esterase	PETCT	CT26 tumor-bearing mice	A pancreatic tumor a few millimeters in size is clearly visible.	[18]
Polymerized liposomal NPs	CA19-9	PET	Pancreatic cancer xenografts in mouse	Pancreatic cancer can be specifically recognized.	[19]
Copper NPs	CC chemokine Receptor 2(CCR2)	PET	Pancreatic ductal adenocarcinoma-bearing mouse	Pancreatic cancer can be detected with high sensitivity and accuracy.	[20]
Polymeric micellar NPs	EGFR	PET	CRC-bearing mouse	The PET imaging of CRC can be enhanced by active targeting.	[21]
Quantum dots	Large external antigen (LEA)	Fluorescence imaging	CRC-bearing mouse	Quantitative analysis of LEA expression in CRC.	[22]
Surface-enhanced Raman scattering NPs	EGFR /HER2	Endoscopy	Esophageal tumor-bearing mice	Visualization of esophageal tumor locations.	[23]
Fluorescent NPs	ASYNYDA peptide	Confocal laser endomicroscopy	Barrett’s esophageal adenocarcinoma-bearing rat	Specific identification of esophageal cancer.	[24]
Polymeric micelles	Glucose-regulated protein 78	SPECT/CT	Gastric cancer-bearing mice	The imaging of gastric cancer can be enhanced.	[25]
Fluorescent magnetic NPs	BRCAA1	Magnetofluorescent imaging	Gastric cancer-bearing mice	Early-stage gastric cancer can be recognized.	[26]
Ultrasmall SPIONPs	Peptide	MRI	HCC-bearing cancer	Early-stage HCC can be identified.	[27]
Upconversion NPs	Peptide	Upconversion luminescence (UCL)/MRI	HCT116 tumor-bearing mice	Sensitive detection of ultra-small colorectal tumors.	[28]
68Ga-labeled Hepatitis E virus NPs	Integrin α3β1	PET	HCT 116 CRC-bearing mice	Internalization of NPs in HCT116 cells is improved significantly, but the specific targeting efficiency needs to be further improved.	[29]
Fe3O4/Au/Ag NPs	Cytidine	SERS	Colon cancer-bearing mice	Detection of nucleoside concentrations at the nM level.	[30]
Human heavy-chain ferritin (HFn) NPs	Transferrin receptor 1 (TfR1)	Endoscopy	Gastric cancer-bearing mice	Identification of early-stage gastric cancer.	[31]
Upconversion NPs	MGb2	MRI	Gastric cancer-bearing mice	Gastric cancer and adjacent lymphatic metastasis sites are detected ultra-sensitively by MRI.	[32]
Magnetic graphitic nanocapsules	Peptidoglycan	MRI	H. pylori-infected mice	H. pylori can be targeted for detection by MRI.	[33]

Figure 1 Improving the imaging function by targeted nanoparticles. The common gastrointestinal tumor biomarkers overexpressed on cell membranes and the typical molecules/ligands used to modify the surface of nanoparticles for targeting imaging.

Abbreviations: CEA, carcinoembryonic antigen; TAG-72, tumor-associated glycoprotein-72; EGFR, epithelial growth factor receptor; HER2, human epidermal growth factor receptor 2; ASGP, asialoglycoprotein.^60,61

Table 2 NP Based Diagnostic Tests for GI Disorders

NP	GI Disease Type	Imaging	Comment	Ref.
Near-infrared fluorescent silica NPs	CRC	Endoscopy	Early-stage CRC(<0.5mm^2) can be detected and depicted in human-scale animal model, which offers a viable pathway for clinical translation for primary CRC detection.	[171]
Anti-CEA loaded maghemite NPs	CRC	SERS	CEA-expressing cells can be identified with high specificity in vitro, providing a potential detection tool for CEA-expressing tumors, micrometastasis, and cancer-circulating cells.	[172]
Carbon NPs	CRC	Laparoscopy	Effective and safe detection of CRC and tracking of lymph nodes is achieved during laparoscopic surgery for CRC.	[173]
AuNPs	CRC	SERS	Non-invasive detection of CRC with high specificity and sensitivity in serum samples.	[174]
UCNPs	CRC	Dual-mode UCL/MRI	Ability to target and detect ultra-small colorectal tumors.	[28]
Gadolinium-loaded solid lipid NPs	CRC	MRI	The NP-based contrast agent can be effectively absorbed by CRC cells to enhance MRI in colorectal tumors.	[175]
QDs	Colon cancer	Endoscopy	Providing an approach for detecting small and flat tumors and improving cancer diagnosis.	[176]
Near-infrared fluorescent proteinoid-poly (L-Lactic Acid) hollow NPs	Colon cancer	NIRF	The hollow NPs are used for the encapsulation of the NIR dye indocyanine green, increasing significantly the photostability of the dye and conjugating with tumor-targeting ligands for specific colon tumor detection.	[177]
Raman scattering NPs	GI cancers	Raman endoscopy	Small precancerous lesions can be detected in animal models, which provides earlier detection method for esophageal, gastric, and colorectal tumors.	[178]
Peptide-coated ultrasmall SIONPs	Liver tumors	MRI	The contrast of MRI in early-stage liver tumors is enhanced.	[27]
Iodinated liposomes	Hepatic tumors	CT	Small liver metastases and vessels can be detected by enhanced CT.	[179]
Lactobionic acid-modified dendrimer-entrapped AuNPs	HCC	CT	HCC can be diagnosed by targeted CT imaging in vivo and in vitro.	[180]
Acetylated polyethylenimine-entrapped AuNPs	HCC	CT	Highly improving the CT contrast enhancement of normal liver and as an effective negative CT contrast agent for diagnosing HCC.	[181]
IONPs	Liver tumors	MRI	Liver tumors can be detected by targeted MRI with ultralow hepatotoxicity.	[182]
Bismuth-based nanoprobes	Liver fibrosis	Spectral CT	Optimizing the prominence of the lesion area and successfully differentiating liver fibrosis from the healthy liver.	[183]
Rhenium sulfide (ReS2) NPs	GI tract	Spectral CT	GI tract can be depicted obviously by spectral CT.	[184]
Nanobubbles	Gastric cancer	US	Nanobubbles are able to pass through the vascular for extravascular ultrasound imaging of tumors in the gastric cancer xenografts.	[185]
Multicolour carbon dots (CDs)	Pancreatic cancer	Fluorescence imaging	CDs can effectively accumulate at tumor site in a murine model of pancreatic cancer and demonstrate excellent fluorescence imaging capabilities, contributing to accurate resection of tumors.	[186]
Copper NPs	Pancreatic ductal adenocarcinoma (PDAC)	PET	^64Cu-radiolabeled nanovehicle allows sensitive and accurate detection of PDAC malignancy by PET imaging in mouse models.	[20]
Dextran-coated cerium oxide NPs (Dex-CeNPs)	IBD	CT	Dex-CeNPs accumulate in the colitis area, producing enhanced CT contrast.	[187]
Lanthanide-doped nanocrystals	IBD	NIRF	Providing a real-time 3D imaging of the GI tract in mice.	[188]

Figure 2 Nanoparticle combined with imaging technique for diagnostic of gastrointestinal disorder.²¹⁹

Figure 3 Multimodal PET and NIRF imaging based on ADSCs derived extracellular vesicles. (A) Schematic illustration showing the generation of exosome use for bio-imaging. (B) NIRF imaging of gastrointestinal tumor-bearing nude mice at different time points (1, 5, 10, 20, 30 and 50 h). The arrows indicate tumor sites. (C) In vitro tissue images at different time points (10, 20 and 30 h) after injection of Cy7-EV-N3.

Abbreviations: M, muscle, LI, large intestine, SI, small intestine, K, kidney, SP, spleen, L, liver, ST, stomach.²⁹¹

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