Dual Functional Gd(III)-DOTA Liposomes for Cancer Therapy and Diagnosis as a Theragnostic Carrier

Abstract

Development of dual functional liposome has been studied for cancer theragnostics. Therefore, we focused on ultrasound-sensitive liposomes with doxorubicin (DOX) and gadolinium (Gd) as a theragnostic carrier having a potential for cancer therapy and diagnosis. In this study, Gd(III)-DOTA-modified sonosensitive liposomes (GL) was developed using chemically synthesized Gd(III)-DOTA-DPPE lipid. Sonosensitivity of GL to 1 MHz ultrasound induced 25% of DOX release. The relaxivities (r 1 ) of GL were 7.33-10.34 mM, which was higher than that of MR-bester ® . Intracellular delivery of DOX from GL by ultrasound irradiation was evaluated according to ultrasound intensity, resulting in increase of uptake of DOX released from ultrasoundtriggered GLs compared to GL3 or Doxil ® without ultrasound. Taken together, this study shows that the paramagnetic and sonosensitive liposomes, GL, is a novel and highly effective delivery system for drug with the potential for broad applications in human disease.

Gadolinium(III)-Chelated Silica Nanospheres Integrating Chemotherapy and Photothermal Therapy for Cancer Treatment and Magnetic Resonance Imaging

“…From the linear correlation between relaxivity and Gd concentration shown in Figure C, the longitudinal relaxivity ( r 1 ) and transverse relaxivity ( r 2 ) of Gd@SiO 2 -DOX/ICG-PDC were 8.5 mM –1 s –1 and 15.9 mM –1 s –1 , respectively. The r 1 value of Gd@SiO 2 -DOX/ICG-PDC was much greater than that of Gd-DTPA ( r 1 = 3.50 mM –1 s –1 ), one of the commonly used commercial MRI T 1 -contrast agent. − The reason is that Gd­(III) can be bound to citrate to produce Gd­(III) core (as shown in Table and Figure ), which restricts the local motions of Gd. Additionally, the r 2 / r 1 ratio is so low that it is beneficial for high signal-to-noise ratio imaging.…”

“…The r 1 value of Gd@SiO 2 -DOX/ICG-PDC was much greater than that of Gd-DTPA (r 1 =3.50 mM −1 s −1 ), 42 one of the commonly used commercial MRI T 1 -contrast agent. [43][44][45][46] The reason is that Gd (III) can be bound to citrate to produce Gd(III) core (as shown in Table 1 and Figure 2), which restricts the local motions of Gd. Additionally, the r 2 /r 1 ratio is so low that is beneficial for high signal-to-noise ratio imaging.…”

Sonosensitive MRI Nanosystems as Cancer Theranostics: A Recent Update

“…In 2013, Han et al developed a sonosensitive system loaded with doxorubicin and endowed of a newly-synthesized Gd-DOTA-DPPE lipid. These vesicles were intended to track drug delivery by MRI, but were unable to report on drug release as Gd 3+ was incorporated in the vesicle membrane, thus preventing the removal of the so-called “quenching effect” (Han et al, 2013 ). Original approaches included the use of a dysprosium chelate (Fowler et al, 2013 ) or Chemical Exchange Saturation Transfer (CEST) contrast agents.…”