Abstract
BackgroundThe rational design of theranostic nanoprobe to present responsive effect of therapeutic potency and enhanced diagnostic imaging in tumor milieu plays a vital role for efficient personalized cancer therapy and other biomedical applications. We aimed to afford a potential strategy to pose both T1- and T2-weighted MRI functions, and thereby realizing imaging guided drug delivery and targeted therapy.ResultsTheranostic nanocomposites Mn-porphyrin&Fe3O4@SiO2@PAA-cRGD were fabricated and characterized, and the nanocomposites were effectively used in T1- and T2-weighted MRI and pH-responsive drug release. Fluorescent imaging also showed that the nanocomposites specifically accumulated in lung cancer cells by a receptor-mediated process, and were nontoxic to normal cells. The r2/r1 ratio was 20.6 in neutral pH 7.4, which decreased to 7.7 in acidic pH 5.0, suggesting the NCs could act as an ideal T1/T2 dual-mode contrast agent at acidic environments of tumor. For in vivo MRI, T1 and T2 relaxation was significantly accelerated to 55 and 37%, respectively, in the tumor after i.v. injection of nanocomposites.ConclusionThe synthesized nanocomposites exhibited highly sensitive MRI contrast function no matter in solution, cells or in vivo by synergistically enhancing positive and negative magnetic resonance imaging signals. The nanocomposites showed great potential for integrating imaging diagnosis and drug controlled release into one composition and providing real-time imaging with greatly enhanced diagnostic accuracy during targeted therapy.
Highlights
The rational design of theranostic nanoprobe to present responsive effect of therapeutic potency and enhanced diagnostic imaging in tumor milieu plays a vital role for efficient personalized cancer therapy and other biomedical applications
Tetraethyl orthosilicate (TEOS) and Igepal CO-520 were purchased from Sigma-Aldrich. 4-dimethylaminopyridine (DMAP), manganese (II) acetate, N-cetyltrimethylammonium chloride (CTAC) and triethanolamine (TEA) were purchased from Sinopharm Chemical Reagent Co., Ltd. c(RGDyK) peptides was purchased from GL Bioche
Fabrication and characterization The formation of the multifunctional magnetic NCs could be divided into 4 steps: (1) the synthesis of the OAcoated Fe3O4 NPs, (2) the successive formation of dense SiO2 and mesoporous SiO2 shells on OA-coated Fe3O4 NPs, (3) the coating of PAA-c(RGDyK) peptides (cRGD) upon the as-synthesized Fe3O4@SiO2 NPs, (4) the loading of Mn-porphyrin into the NPs
Summary
The rational design of theranostic nanoprobe to present responsive effect of therapeutic potency and enhanced diagnostic imaging in tumor milieu plays a vital role for efficient personalized cancer therapy and other biomedical applications. The magnetic resonance imaging (MRI) technique has been introduced to clinic to provide multiplanar imaging for the soft tissues in the body without invasion. Because of its superb soft tissues imaging contrast, multidimensional imaging function, and absent of ionizing radiation, MRI is becoming increasingly available for clinical imaging [1]. Contrast agents (CAs) are widely employed in the MRI, for which over 200 million doses had been administered [3]. The most frequently used reagents for contrast enhancement are gadolinium-based, such MRI contrast agents are representative T 1 contrast agents that can effectively curtailing the T1 relaxation time of protons inside tissues by interactions with the neighboring contrast agent [4]. All clinically approved Gd-CAs are small molecules.
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