Table 2: Summary of the all discussed nanoparticle formulations used for colorectal cancer detection and imaging, for each formulation size, zeta potential, targeting strategy, administration route, payload, in vitro and in vivo models they have been tested on, the relative results, and references.

NanovectorSize (AVG)ChargeTargeting strategyPayloadAdministration routeModelResultsReferences

Anti-CEA MoAB-PAMAM-NIR664-doped silica NPs70 nmEPR
Anti-CEA MoAB
NIR664IVIn vitro: LS174 T, LoVo and HCT116 cell cultures
In vivo: LS174 T subcutaneously injected in nude mice.
In vitro: Increased uptake compared with untargeted formulation.
In vivo: Increased tumor-associated fluorescence compared to untargeted formulation.
[43]

FMSNs-UEA175 nm–13 mVEPR
Α-L-fucose targeting
FITCTopicalIn vitro: HCT116 (α-L-fucose +) and Caco-2 (α-L-fucose +) cell lines
Ex vivo: colonic mucus from A/J mice and colon tissue from DSS/AOM-induced CRC bearing A/J mice
In vivo: DSS/AOM-induced CRC in A/J mice
In vitro: targeting of α-L-fucose + cell lines
Ex vivo: good stability in mucus and binding to α-L-fucose + tissue.
In vivo: marked NPs binding to CRC regions demonstrated by endomicroscopy
[44]

P(PE-PLLA)103 nm–30 mVCEA active targetingFluorescent dye:
ICG
IV (biodistribution)
Intraluminal administration
In vitro: SW480 and HT29 cell lines and CAM-engrafted cells
In vivo: BALB/c male mice (biodistribution, and LS174 t cells intracolinically implanted in nude BALB/c male mice
In vitro: CEA expression and anti-CEA AB (targeting moiety) dependent tumor binding
In vivo: wide biodistribution after IV administration, good CRC detection after topical administration
[45]

HPMA-EPPT1-IR783uMUC-1 active targetingNIRF dye:
IR-783
Intraluminal administrationIn vitro: uMUC-1(++) HT29, uMUC-1 (+) LS174 t and uMUC-1 (–) SW480 cell lines
Ex vivo: CRC and healthy tissue patient matched samples
In vivo: LS174 t or HT29 administered in the colon wall of athymic female nude mice.
In vitro: uMUC-1 dependent conjugate tumor-binding of targeted formulation
Ex vivo: selective binding to CRC tissues of targeted formulation.
In vivo: good tumor binding and detection.
[46]
EGFR/VEGF-F-SERSA/B350 nmEGFR/VEGF active targetingFluorescent dye: AF610 SERS dyes: RITC and FITC (EGFR and VEGF, respectively)TopicalIn vitro: HT-29 CRC cell line retroviral-transfected with luciferase DNA
In vivo: transfected HT-29 cells injected in BALB/c nude mice in the colon wall.
In vitro: efficient cell labelling proportional to cell density and administered dose.
In vivo: multimodal detection of small tumours in real time with high sensitivity and EGFR/VEGF profiling.
[48]

CNPsLN tropism and retentionEndoscopic submucosal administration152 rectal cancer patientsEnhanced LNs detection, quicker surgical removal of more LNs, leading to better nodal staging[50]

FA-3WJ-pRNA NPsEPR
FRα active targeting
Alexa fluor-647IVIn vitro: KN20 and HT 29 cell lines
In vivo: nude mice model of CRC liver and lung metastasis
In vitro: FA-dependent cell binding and uptake
In vivo: CRC metastasis targeting and avoidance of healthy parenchyma.
[51]

CNPs150 nmLN tropism and retentionEndoscopic submucosal administration74 CRC T1 and T2 patientsEnhanced tracking if sentinel lymph node with near 100% accuracy in metastasis labelling.[80]

Abbreviations: Avg: average; CRC: colorectal cancer; DOX: doxorubicin; EPR: enhanced permeability and retention effect; IV: intravenous; SC: subcutaneous; LN: lymph node; PDT: Photodynamic treatment; PTT: photothermal treatment.