A platinum anticancer theranostic agent with magnetic targeting potential derived from maghemite nanoparticles

Abstract

Superparamagnetic iron oxide nanoparticles (SPION) are potential drug carriers and a magnetic resonance imaging (MRI) contrast agent for cancer therapy and diagnosis. In this study, dechlorinated cisplatin (CMDP) is tethered to maghemite nanoparticles modified with 4-oxo-4-(3-(triethoxysilyl)propylamino)butanoic acid (OTPBA-SPION) through the surface carboxylate groups. The nanocomposite (CMDP-OTPBA-SPION) was characterized by TEM, XPS, EDX, SQUID, ICP-AES, and zeta potential. A relatively high Pt loading capacity (ca. 13%) is achieved with this drug delivery system. The DNA binding ability of CMDP-OTPBA-SPION is prominent in acidic medium (pH 5.2) but is insignificant under normal physiological conditions (pH 7.4), suggesting that an acidic cancerous environment is favourable for the release of the platinum pharmacophore from the composite. The transverse relaxivity of CMDP-OTPBA-SPION in phosphate-buffered saline is 141.9 mM À1 s À1 in terms of Fe concentration, implying that the composite could be used as a negative-contrast agent for MRI. The cytotoxicity of the composite toward MCF-7 and HeLa cancer cells displays slow and time-dependent characteristics, reaching a level comparable to that of cisplatin at 72 h. The diagnostic capability and tumor-specific accumulation of the composite are verified in vitro and in vivo by the time-dependent negative-contrast enhancement effect in MRI using MCF-7 cells and tumor-bearing mice, respectively. The results demonstrate that CMDP-OTPBA-SPION can potentially be used as an anticancer theranostic agent for simultaneous targeted therapy and MRI under an external magnetic field.

Enhancing Tumor Cell Response to Chemotherapy through the Targeted Delivery of Platinum Drugs Mediated by Highly Stable, Multifunctional Carboxymethylcellulose‐Coated Magnetic Nanoparticles

“…For example, the immobilization of cisplatin onto carboxy‐functionalized superparamagnetic iron oxide nanoparticles (SPION) in the work of Wang et al . did not result in an improved cytotoxic effect when compared with free cisplatin.…”

Impact of serum proteins on MRI contrast agents: cellular binding and T2relaxation

“…The decay rate is not only dependent on iron oxide concentration, but also on temperature, particle size, and coating of the iron oxide cores. 8, 9, 75 To determine if the protein corona affected the T 2 relaxation time, we carried out the same measurement using isolated soft corona-SPIONs (Fig. 6B).…”

Platinum(II)–Gadolinium(III) Complexes as Potential Single‐Molecular Theranostic Agents for Cancer Treatment

“…[8] We recently showed that Pt drugs could be attached to Fe 2 O 3 nanoparticles to form anticancer theranostic agents, in which nanoparticles act as both drug carriers and T 2 -weighted MRI contrast agents (CAs). [9] However, release procedures are indispensable for these nanomedicines. As alternatives, Gd III complexes are widely used as T 1 -weighted CAs in MRI through the interaction of innersphere water with paramagnetic Gd III and rapid exchange of the coordinated water with the bulk solvent.…”