DOTA Functionalized Cross-Linked Small-Molecule Micelles for Theranostics Combining Magnetic Resonance Imaging and Chemotherapy

Abstract

Herein, a new theranostic nanoplatform was built by introducing DOTA on the surface of the cross-linked small molecular micelles. This nanoplatform consisted of three parts: (1) Hydrophobic alkyl chain functioned with alkenes as cross-linkable part to ensure the robust stability in vivo; (2) Hydrophilic DOTA for not only gadolinium ions complexion as MR imaging contrast agents but also platinum ions complexion as drug carriers; (3) Cisplatin as antitumor drug and MR imaging amplifier simultaneously. The metal loading content of the resulting Pt/Gd@DOTA-CSMs was up to 12 and 14 wt % for Gd(III) and Pt(II), respectively. The longitudinal relaxation rate of Gd@DOTA-CSMs (8.46 mM s) was 2.6 times than that of the clinical Gd-DTPA (3.23 mM s). When cisplatin was involved, not only great antitumor efficiency was achieved, but higher longitudinal relaxation rate of Pt/Gd@DOTA-CSMs (11.17 mM s) was carried out due to the extension of rotational correlation time. The experiments of Balb/c mice bearing 4T1 xenograft indicated that Pt/Gd@DOTA-CSMs had better antitumor activity, lower side effect than clinically used cisplatin, and greater MR imaging than Gd-DTPA. All the results proved that the nanoplatform of DOTA-CSMs held remarkable potential in the field of therapeutics.

Copper(I)‐Chelated Cross‐Linked Cyclen Micelles as a Nanocatalyst for Azide‐Alkyne Cycloaddition in Both Water and Cells

“…Notably, the average diameter of cCMs was around 45.0 nm (Figure a), a little bit larger than that of CMs. This is reasonable considering that the cross‐linking agents were introduced into the micelle core after cross‐linking …”

“…The cross‐linked small‐molecule micelles (cSMs) are covalently surface‐ or core‐captured spherical micelles assembled by the amphiphiles with typically molecular weight below 1000.0 Da . Featuring the dendrimer‐like properties (e. g., spherical shape, controllable size, functionalized exterior, and good stability), the cSMs have been shown to be a good alternative to dendrimers in many applications .…”

“…The cross‐linked small‐molecule micelles (cSMs) are covalently surface‐ or core‐captured spherical micelles assembled by the amphiphiles with typically molecular weight below 1000.0 Da . Featuring the dendrimer‐like properties (e. g., spherical shape, controllable size, functionalized exterior, and good stability), the cSMs have been shown to be a good alternative to dendrimers in many applications . In organic synthesis, the cSMs supported rhodium catalyst, zinc complex, gold(0) nanoclusters, and copper(0) nanoparticles have successfully been developed to catalyze various organic reactions in aqueous phase with excellent catalytic efficiency, selectivity, and recyclability.…”

Facile Transfer of Reverse Micelles from the Organic to the Aqueous Phase for Mimicking Enzyme Catalysis and Imaging-Guided Cancer Therapy

“…Also, utilizing the confined water pools and hydrophobic alkyl chains, the WICRMs were further employed as platforms for image-guided cancer therapy. The integration of imaging into drug delivery systems has been demonstrated to be a promising strategy for disease treatment since it can monitor in real time the distribution of nanodrugs. − …”

Simple Host–Guest Assembly for High-Resolution Magnetic Resonance Imaging of Microvasculature

“…They are characterized by their high molecular weight and large size, preventing redistribution from the blood vessels into the interstitial space. , BPCAs reside in the vascular system for an extended period of time and can provide highly resolved vascular structure images. Most examples of BPCAs are Gd chelates covalently bonded to or encapsulated in macromolecular constructs such as polymers, − dendrimers, − liposomes, − micelles, − and nanoparticles. − However, many of them have several shortcomings, including poor renal filtration, hepatobiliary uptake, and long-term tissue accumulation, causing toxicity. − Biodegradable or renal clearable BPCAs have been studied as an alternative. − …”