Ye Kuang

Hydrophobic IR-780 Dye Encapsulated in cRGD-Conjugated Solid Lipid Nanoparticles for NIR Imaging-Guided Photothermal Therapy

This is high demand to enhance the accumulation of near-infrared theranostic agents in the tumor region, which is favorable to the effective phototherapy. Compared with indocyanine green (a clinically applied dye), IR-780 iodide possesses higher and more stable fluorescence intensity and can be utilized as an imaging-guided PTT agent with laser irradiation. However, lipophilicity and short circulation time limit its applications in cancer imaging and therapy. Moreover, solid lipid nanoparticles (SLNs) conjugated with c(RGDyK) was designed as efficient carriers to improve the targeted delivery of IR-780 to the tumors. The multifunctional cRGD-IR-780 SLNs exhibited a desirable monodispersity, preferable stability and significant targeting to cell lines overexpressing αvβ3 integrin. Additionally, the in vitro assays such as cell viability and in vivo PTT treatment denoted that U87MG cells or U87MG transplantation tumors could be eradicated by applying cRGD-IR-780 SLNs under laser irradiation. Therefore, the resultant cRGD-IR-780 SLNs may serve as a promising NIR imaging-guided targeting PTT agent for cancer therapy.

Gadolinium-based nanoscale MRI contrast agents for tumor imaging

Gadolinium-based nanoscale magnetic resonance imaging (MRI) contrast agents (CAs) have gained significant momentum as a promising nanoplatform for detecting tumor tissue in medical diagnosis, due to their favorable capability of enhancing the longitudinal relaxivity (r1) of individual gadolinium ions, delivering to the region of interest a large number of gadolinium ions, and incorporating different functionalities. This mini-review highlights the latest developments and applications, and simultaneously gives some perspectives for their future development.

Poly(glycerol) Used for Constructing Mixed Polymeric Micelles as T1 MRI Contrast Agent for Tumor-Targeted Imaging

There was much interest in the development of nanoscale delivery vehicles based on polymeric micelles to realize the diagnostic and therapeutic applications in biomedicine. Here, with the purpose of constructing a micellar magnetic resonance imaging (MRI) contrast agent (CA) with well biocompatibility and targeting specificity, two types of amphiphilic diblock polymers, mPEG-PG(DOTA(Gd))-b-PCL and FA-PEG-b-PCL, were synthesized to form mixed micelles by coassembly. The nanostructure of the resulting micellar system consisted of poly(caprolactone) (PCL) as core and poly(glycerol) (PG) and poly(ethylene glycol) (PEG) as shell, simultaneously modified with DOTA(Gd) chelates and folic acid (FA), which afforded functions of MRI contrast enhancement and tumor targeting. The mixed micelles in aqueous solution presented a hydrodynamic diameter of about 85 nm. Additionally, this mixed micelles exhibited higher r1 relaxivity (14.01 mM-1 S1-) compared with commercial Magnevist (3.95 mM-1 S1-) and showed negligible cytotoxicity estimated by WST assay. In vitro and in vivo MRI experiments revealed excellent targeting specificity to tumor cells and tissue. Furthermore, considerably enhanced signal intensity and prominent positive contrast effect were achieved at tumor region after tumor-bearing mice were intravenously injected with the mixed micelles. These preliminary results indicated the potential of the mixed micelle as T1 MRI CA for tumor-targeted imaging.

Hyperbranched poly(glycerol) as a T1 contrast agent for tumor-targeted magnetic resonance imaging in vivo

Correction for ‘Hyperbranched poly(glycerol) as a T1 contrast agent for tumor-targeted magnetic resonance imaging in vivo’ by Yi Cao, et al., Polym. Chem., 2017, DOI: 10.1039/c6py01819j.

PEGylated chitosan grafted with polyamidoamine-dendron as tumor-targeted magnetic resonance imaging contrast agent

Macromolecular contrast agents labeled with targeting ligands are now receiving growing interest in tumor-targeted magnetic resonance imaging. In this study, a macromolecular contrast agent based on PEGylated chitosan was synthesized and characterized, and its application as an MRI contrast agent was then demonstrated both in vitro and in vivo. First, the chitosan backbone was partially grafted with poly(ethylene glycol), which was used to improve the in vivo stability, followed by modifying with azide groups. Second, alkynyl-terminated PAMAM dendron modified with gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) was synthesized and conjugated onto the chitosan backbone through click chemistry. Finally, the obtained mCA was further functionalized with folic acid to improve the target specificity. The obtained FA labeled mCA exhibited higher relaxivity (9.53 mM−1 s−1) relative to Gd-DTPA (4.25 mM−1 s−1) and showed negligible toxicity as determined by the WST assay. In vivo MRI results suggested that a relatively high signal enhancement was observed in the tumor region, which made it a promising candidate for tumor-targeted MRI CA.

Multi-arm star-branched polymer as an efficient contrast agent for tumor-targeted magnetic resonance imaging

Contrast agents with high efficiency and safety are excellent candidates as magnetic resonance imaging probes. Herein, a multi-arm star-branched polymer was prepared by conjugating oligolysine onto a rigid hyperbranched poly(amido amine) core via click chemistry, followed by covalent modification with Gd chelate and folic acid (FA-OLL-g-HBPAMAM-DTPA-Gd). This multi-arm star-branched polymer contrast agent exhibited much higher longitudinal relaxivity (r1 = 13.34 mM-1 s-1) as compared to a commercial contrast agent (Gd-DTPA, r1 = 4.2 mM-1 s-1). No obvious histological toxicity was observed from histological assessment, which illustrated that FA-OLL-g-HBPAMAM-DTPA-Gd exhibited excellent biocompatibility. Both in vitro and in vivo MRI studies showed that the macromolecular contrast agent provided better signal contrast enhancement and presented obvious target specificity to KB xenografts with a sufficient time window for MRI scanning; moreover, this multi-arm star-branched mCA has great potential for developing sensitive and biocompatible MRI CA with targeting ability.

Aptamer-Targeted Magnetic Resonance Imaging Contrast Agents and Their Applications

Magnetic resonance imaging is a powerful diagnostic technology with high spatial resolution and non-invasion. The contrast agents have significant effect on the resolution of the MR imaging. However, the commercial contrast agents (CAs) usually consist of individual Gd3+ chelated with a low molecular weight acyclic or cyclic ligand, and these small-molecule CAs are usually subjected to nonspecificity, thus leading to rapid renal clearance and modest contrast enhancement for tumor imaging. In recent years, the nanostructured materials conjugated with aptamers were widely used and opened a new door in biomedical imaging due to excellent specificity, non-immunogenicity, easily synthesis and chemical modification of aptamers. This review summarizes all kinds of aptamertargeted MRI CAs and their applications.

Gadolinium(III)-based Polymeric Magnetic Resonance Imaging Agents for Tumor Imaging

Contrast agents (CAs) are widely used to improve the signal-noise ratio in the magnetic resonance imaging (MRI) examinations. The majority of MRI CAs used in clinic are gadolinium( III) (Gd(III)) chelates with low molecular weight. Compared with these small-molecule CAs, Gd(III)-based polymeric magnetic resonance imaging agents (i.e. macromolecular contrast agents, mCAs), prepared by conjugating small-molecule Gd(III) chelates onto macromolecules, possess high relaxivity and relative long blood circulation time, which are favorable for MRI examinations. In last decades, increasing attention was paid to the design of mCAs with various structures, and further evaluation of the MRI performance both in vitro and in vivo. Herein, we focus on the recent progress of mCAs, including structures, properties and applications. Meanwhile, this review also highlights the emerging MRI mCAs with smart response and multi-function: tumor microenvironment- stimulated MRI, multi-mode imaging and MRI-based theranostics.

Biodegradable Nanoglobular Magnetic Resonance Imaging Contrast Agent Constructed with Host–Guest Self-Assembly for Tumor-Targeted Imaging

Gadolinium-based macromolecular magnetic resonance imaging (MRI) contrast agents (CAs) have attracted increasing interest in tumor diagnosis. However, their practical application is potentially limited because the long-term retention of gadolinium ion in vivo will induce toxicity. Here, a nanoglobular MRI contrast agent (CA) PAMAM-PG- g-s-s-DOTA(Gd) + FA was designed and synthesized on the basis of the facile host-guest interaction between β-cyclodextrin and adamantane, which initiated the self-assembly of poly(glycerol) (PG) separately conjugated with gadolinium chelates by disulfide bonds and folic acid (FA) molecule onto the surface of poly(amidoamine) (PAMAM) dendrimer, finally realizing the biodegradability and targeting specificity. The nanoglobular CA has a higher longitudinal relaxivity ( r1) than commercial gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA), showing a value of 8.39 mM-1 s-1 at 0.5 T, and presents favorable biocompatibility on the observations of cytotoxicity and tissue toxicity. Furthermore, MRI on cells and tumor-bearing mice both demonstrate the obvious targeting specificity, on the basis of which the effective contrast enhancement at tumor location was obtained. In addition, this CA exhibits the ability of cleavage to form free small-molecule gadolinium chelates and can realize minimal gadolinium retention in main organs and tissues after tumor detection. These results suggest that the biodegradable nanoglobular PAMAM-PG- g-s-s-DOTA(Gd) + FA can be a safe and efficient MRI CA for tumor diagnosis.

Geometrical Confinement of Gadolinium Oxide Nanoparticles in Poly(ethylene glycol)/Arginylglycylaspartic Acid-Modified Mesoporous Carbon Nanospheres as an Enhanced T1 Magnetic Resonance Imaging Contrast Agent

A new strategy for designing contrast agents (CAs) based on geometrical confinement will become a competent way to improve the relaxivity of CAs. Herein, a magnetic resonance imaging (MRI) nanoconstruct is fabricated through loading Gd2O3 nanoparticles into mesoporous carbon nanospheres, followed by conjugation of poly(ethylene glycol) (PEG) and the c(RGDyK) peptide (Gd2O3@OMCN-PEG-RGD), which could prolong the blood circulation half-life as well as improve the tumor-targeting ability. As a result, the Gd2O3@OMCN-PEG-RGD exhibits an outstandingly high relaxivity ( r1 = 68.02 mM-1 s-1), which is ∼5.3 times higher than that of Gd2O3 nanoparticles ( r1 = 12.74 mM-1 s-1). Afterward, both the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test and H&E staining show that the Gd2O3@OMCN-PEG-RGD has wonderful biocompatibility in vitro and in vivo. Moreover, the in vivo MR images indicate that the Gd2O3@OMCN-PEG-RGD could accumulate in the tumor region more rapidly than Gd2O3@OMCN-PEG. This study presents a facile method to fabricate an MRI CA with excellent T1 contrast ability based on geometrical confinement and excellent biocompatibility, which could act as an optimal contender for sensitive in vivo tumor imaging with outstanding targeting ability.