Magnetic resonance imaging-guided and targeted theranostics of colorectal cancer

Yanan Li; Jingqi Xin; Yongbing Sun; Tao Han; Hui Zhang; Feifei An

doi:10.20892/j.issn.2095-3941.2020.0072

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Figure 1
The site-selective delivery of TNPs via the hepatic portal vein and photothermal therapy under a catheter-based 808 nm near infrared laser. Reprinted with permission from Ref. 124, Parchur AK, Sharma G, Jagtap JM, Gogineni VR, LaViolette PS, Flister MJ, et al. Vascular interventional radiology-guided photothermal therapy of colorectal cancer liver metastasis with theranostic gold nanorods. ACS Nano. 2018; 12: 6597-611. Copyright@ American Chemical Society.

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Table 1

Description of chemical preparation methods of MNPs and their strength and weaknesses

Method	Procedure	Strength	Weakness	Reference
Co-precipitation	The precipitation of metal salts under alkaline conditions to produce MNPs at room temperature or elevated temperature	Facile, convenient Cost-effective Easy to implement Less hazardous reagents Large-scale preparation	Unstable Polydisperse	⁷¹
Thermal decomposition	The decomposition of organometallic compounds and oxidation in high boiling point organic solvents containing stabilizing surfactants	Highly monodisperse Controlled structure and performance	High temperature Complicated MNPs dissolved in non-polar solvents	⁷²
Hydrothermal	A phase transfer and separation process at the interfaces of the liquid, solid, and solution phases at high temperature (130–250 °C) and high pressure (0.3–4 MPa)	Simple Low cost Water dispersible Controlled morphology High purity and crystallinity	High temperature High pressure	⁷³
Microemulsion	MNPs are generated by mixing inorganic salt and precipitating agent contained in the oil/water or water/oil nanodroplets	Adequate Versatile Controlled size and shape	Low yield Complicated purifying procedure	⁷⁵
Sol-gel	Hydrolysis and polycondensation of metal precursors, metal, or metalloid element surrounded by various reactive ligands to form a “sol,” then dried by solvent removal or chemical reaction to form “gel,” followed by heat treatment for MNP harvesting	Pure Stoichiometric Monodisperse Large size Controlled structure	Low stability in aqueous solution	^76,77
Polyol synthesis	It is based on a transfer and separation mechanism occurring at the interfaces of the metal precursor (solid), organic solvent (liquid) and water solution containing polyol derivatives.	Simple, reproducible Monodisperse Controlled morphology Cost effective Good crystallinity Excellent magnetic property	High temperature High pressure Toxic organic solvents	⁷⁸

MNPs, magnetic nanoparticles.

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Table 2

Polymer-based encapsulation techniques of MNPs

Methods	Procedure	Description	Reference
Nanoprecipitation	Dropwise addition of organic solution containing preformed polymer and MNPs into an aqueous phase with or without surfactant, under moderate agitation, the nanocapsules are instantaneously formed on the interface of both phases	Two phases are miscible Organic solvents are highly volatile Organic phase can be a mixed solvent Aqueous phase can be a mixed non-solvent	⁸¹
SEE	It consists of simple emulsion formation, solvent evaporation, polymer precipitation, and particles formation	There are oil/water and water/oil methods Organic phase should be non-miscible but can dissolve polymers Particle characteristics are controlled by adjusting procedure parameters, such as organic/water ratio, surfactant, stirring rate, polymer amount, and evaporation rate	⁸²
DEE	Primary emulsion: dispersion of an aqueous phase containing MNPs in a non-miscible organic solvent under ultrasound and surfactant Second emulsion: the primary dispersion is added to a second solution containing the stabilizing agent under sonication Nanocapsules formation: NPs are obtained after evaporation of the solvents	It is classified as W/O/W or O/W/O emulsion It is suitable for the co-encapsulation of both hydrophilic and hydrophobic drugs and/or MNPs	⁸³
LBL	LBL is a stepwise adsorption and assembly process based on spontaneous electrostatic attraction between oppositely charged components at supersaturating polyelectrolyte concentration, which leads to the adsorption of polyelectrolyte onto an oppositely charged particles surface	It is possible to control the size, shape, and thickness of multilayer nanocapsules The polymer should have sufficiently charged groups to provide stable adsorption on the oppositely charged surface Besides electrostatic interaction, hydrogen bonding and covalent bonding are also drivers for multilayer nanocapsule preparation	⁸⁴

NPs, nanoparticles; MNPs, magnetic nanoparticles; W/O/W, water-oil-water; O/W/O, oil-water-oil.

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Table 3

The theranostic applications of MNPs-based DDS in colorectal cancer treatment

NanoDDS	Preparation method	Tumor model	Diagnostic mode	Therapeutic mode	In vivo efficacy	Reference
PTX-SPIO-PEALCa micelle	Polymer self-assembly	LoVo xenograft tumor	MRI	Chemotherapy	The tumor volumes of PTX-SPIO-PEALCa, Taxol, and PBS groups at day 30 were 65.0 ± 8.4, 598.7 ± 77.4, and 1050.7 ± 54.4 mm³, respectively	¹¹²
PTX-PFOB-(PLGA-PEG)	Emulsion evaporation	CT-26 xenograft tumor	MRI	Chemotherapy	Two-fold reduction of tumor growth compared to control and Taxol^® groups	¹¹³
5-FU-magnetite-PLGA	O/W/O/W multiple emulsion and solvent evaporation	CT-26 allograft model	MRI	Chemotherapy	The nanocapsules showed more efficient tumor volume inhibition (100 mm³ at day 21) than 5-FU alone (1500 mm³)	¹¹⁴
Cisplatin-magnetite-P(MAA-g-EGMA)	Hydrolytic alkaline precipitation	HT-29 xenograft tumor	MRI PET CT	Chemotherapy	The tumor volumes of nano-assemblies+external magnetic field, nano-assemblies, and free cisplatin at day 38 were 300, 400, and 900 mm³, respectively	¹¹⁵
Oxaliplatin-SPIO-MWNTs-PEG	Polyol process	HCT-116 tumor-bearing mice	MRI	Chemotherapy	Nanotheranostics showed more effective tumor inhibition than oxaliplatin, with trivial weight loss (6.25%) and organ toxicity	¹¹⁶
PTX-F127-SIONR	Hydrothermal method	CT-26 xenograft tumor	MRI	Chemotherapy	PTX-F127-SIONR exhibited higher therapeutic response and lower tumor growth than PTX group, which showed comparable tumor size to control group, and 100% death at day 34	¹¹⁷
DOX-Fe₃O₄ MNPs	Co-precipitation	HT-29 cells in vitro	MRI	Chemotherapy	DOX-MNPs showed higher cytotoxicity (IC50 = 0.245 μmol/L) than free DOX (IC₅₀ = 0.757 μmol/L)	¹¹⁸
MANPs-PTX	One step oxidation method	CT-26 xenograft tumor	MRI	Chemoradiation therapy	MANPs-PTX inhibited tumor growth of 96.57%; other treatments showed insufficient efficacy	¹¹⁹
Anti-MG1-HNPs	High temperature hydrolysis reaction	CC-531-implanted Wistar rats	MRI	PTA	The tumor inhibition rates of anti-MG1-HNPs, HNPs, and control groups were 38% ± 29%, 14% ± 17%, and 7% ± 8%, respectively	¹²⁰
Aptamer-Au@SPIONs	Microemulsion	HT-29 cells in vitro	MRI	PTT	80% cell inhibition rate, at 500 µg/mL system concentration and 820 nm NIR exposure	¹²¹
Au-HNPs-scFv	–	SW1222 xenograft tumor	MRI	PTT	The tumor volumes of HNPs-scFv, laser only, non-targeted HNPs, and control groups were 72 ± 7, 161 ± 15, 195 ± 10, and 193 ± 18 mm³, respectively	¹²²
A33scFv-HNPs	Thermal decomposition	SW1222 cellsHT-29 cells in vitro	MRI	PTT	After 6 min treatment of 808 nm laser, > 53% of SW1222 cells were involved with apoptosis-related cell death while < 5% occurred in HT-29 cells	¹²³
Au@Gd₂O₃:Ln (Ln = Yb/Er)	Seed-mediated growth method	CC-531 xenograft tumor	MRI	PTT	Under 808 nm NIR light irradiation for 5 min, the tumor temperature increased by ~19.5 °C in the NPs group, showing a stronger PTT effect than the control (~7.5 °C)	¹²⁴
HANs	Thermal decomposition	HT-29 xenograft tumor	MRI PAI	Chemotherapy PTT	The tumor volume of the HANs+laser group remained ~0 without a relapse, which was reduced slightly in the HANs alone group, while the tumor grew rapidly after laser treatment without the HANs and PBS groups	¹²⁵
MGO-PEG-CET	Co-precipitation	CT-26 BALB/c mice	MRI	Chemotherapy PTT	The relative tumor volumes of control, DOX, MGO-PEG-CET/DOX, MGO-PEG-CET/DOX+magnet, and MGO-PEG-CET/DOX+magnet+laser were 12.1, 10.1, 9.5, 5.8, and 0.42, respectively	¹²⁶
Fe-CPNDs	Coordination reaction	SW620 xenograft tumor	MRI	PTT	Complete tumor ablation at day 20	¹²⁷
Hypericin-SPIONs	Co-precipitation	HT-29 cells in vitro	MRI	PDT	Cell proliferation was completely abolished at 2 µmol/L of hypericin and 60 h of illumination time	¹²⁸
SiRNA plasmid-Au	–	LoVo bearing nude mice	MRI	Gene therapy	Bag-1 protein level was silenced to 60% of control, and caused the debasement of Wnt pathway	¹²⁹
SN-38/USPIO-siRNA-PEG	O/W emulsion and solvent evaporation	LS174T bearing nude mice	MRI	Chemotherapy Gene therapy	The tumor volumes of SN-38/USPIO/siRNA, SN-38/USPIO, and SN-38 groups were 340 ± 52, 591 ± 125, and 1,150 ± 362 mm³, respectively	¹³⁰

SPIO, superparamagnetic iron oxide; SIONR, SPIO nanorods; USPIO, ultra-small SPIO; Fe₃O₄, iron-oxide; PFOB, perfluorooctyl bromide; MWNTs, multiwalled carbon nanotubes; MNPs, magnetic nanoparticles; MnO₂, manganese dioxide; HNPs, hybrid magnetic gold nanoparticles; HANs, hybrid anisotropic nanoparticles; CPNDs, coordination polymer nanodots; Au, gold; Gd, gadolinium; Ln, lanthanide; Yb, ytterbium; Er, erbium; MGO, magnetic graphene oxide; PEALCa, PEG-P(Asp-DIP)-P(Lys-Ca); PEG, polyethylene glycol; P(Asp-DIP), poly(N-(N′,N′-diisopropylaminoethyl) aspartamide); P(Lys-Ca), poly (lysine-cholic acid); PLGA, poly(lactide-co-glycolide); P(MAA-g-EGMA), poly(methacrylic acid)-g-poly(ethyleneglycol methacrylate); F127, pluronic F127; MANPs, MnO₂ functioned albumin nanoparticles (ANPs); PTX, paclitaxel; 5-FU, 5-fluorouracil; DOX, doxorubicin; SN-38, 7-ethyl-10-hydroxycamptothecin; PBS, phosphate-buffered saline; O, oil; W, water; IC₅₀, half maximal inhibitory concentration; MG1 mAbs, a monoclonal antibody localized to rat colorectal liver metastasis cells; scFv, single-chain variable fragment; A33, an antigen presented on some CRC cells such as SW1222; CET, cetuximab, an EGFR monoclonal antibody; siRNA, small interfering RNA; Bag-1, Bcl-2-associated athanogene 1; MRI, magnetic resonance imaging; PET, positron emission tomography; CT, computed tomography; PAI, photoacoustic imaging; PTA, photothermal ablation; PTT, photothermal therapy; PDT, photodynamic therapy; NIR, near infrared; CRC, colorectal cancer, LoVo cells, human CRC cells; CT-26 cells, murine colon cancer cells; HT-29 cells, human colon cancer cells; HCT-116 cells, human colon cancer cells; CC-531 cells, rat colorectal liver metastasis cells; SW1222 cells, human CRC cells; SW620 cells, human CRC cells; LS174T cells, human colon cancer cells; DDS.