Prolonged Circulating Lipid Nanoparticles Enabled by High-Density Gd-DTPA-Bis(stearylamide) for Long-Lasting Enhanced Tumor Magnetic Resonance Imaging

Abstract

Porphysomes (PS) were explored to incorporate different types of diethylenetriaminepentaacetic-acid-gadolinium-(III) (Gd-DTPA)-lipids into their bilayer membrane to assess PS potential as an MRI contrast agent. The Gd-dPS-BSA by integration of over 30% Gd-DTPA-bis(stearylamide) (Gd-DTPA-BSA)-lipids in PS construction resulted in exceptional serum stability and T1 and T2 relaxivity measurements of 13 mM–1 s–1 and 19 mM–1 s–1, respectively. The Gd-dPS-BSA demonstrated significantly enhanced retention in blood circulation with a half-life of 13.6 h and high tumor accumulation up to 19.5%ID/g at 72 h post-injection in select cancer mouse models. Additionally, Gd-dPS-BSA displayed excellent MRI tumor enhancement over 24, 48, and 72 h with contrast enhancements from the baseline of 35.8%, 38.2%, and 38.3%, respectively. Results reported here highlight a high-density incorporation of Gd-DTPA-BSA-lipids within PS, and other liposome formulations can enhance circulatory longevity, independently of particles’ concentration, suggesting effective MRI contrast agent potential for Gd-dPS-BSA and potential utility of Gd-DTPA-BSA-lipids to enhance other liposomal-influenced diagnostic and therapeutic functions.

Novel Strategy to Drive the Intracellular Uptake of Lipid Nanoparticles for Photodynamic Therapy

“…To determine the potential effect of other aminopolycarboxylic acid head‐lipid conjugates on enhancing the uptake of the PS NP, diethylenetriamine pentaacetate‐hexadecylamide lipid (DTPA‐lipid) was selected for PS construction since DTPA possesses similar structure to EDTA, and is a clinically approved MRI contrast agent when chelated with gadolinium [11] . A dPS formulation containing DTPA‐lipid (DTPA‐PS, dPS) was synthesized [11c] by replacing the EDTA‐lipid content in ePS formulation (Table S1, Figure S5). A quantitative cellular uptake study revealed no significant difference in the uptake of ePS and dPS in KB cells regardless of incubation time; however, their uptake was significantly greater compared to PS (p<0.05, Figure 2A).…”

Magnetic Resonance Diagnosis of Early Triple-Negative Breast Cancer Based on the Ionic Covalent Organic Framework with High Relaxivity and Long Retention Time

“…Clinically, the optimal time window for MR imaging (10–15 min) is close to the half-life of commercial CAs, which should be imaged immediately after Gd-chelate administration . The slightly longer half-life of Mn-iCOF overcame the problems of commercial CAs (too short) or some nanoparticles that were reported with half-lives of several hours or even longer time (too long). , …”

“…62 The slightly longer half-life of Mn-iCOF overcame the problems of commercial CAs (too short) or some nanoparticles that were reported with half-lives of several hours or even longer time (too long). 63,64 As shown in Figure 6B−C, the T 1 WI signals in the kidney and liver appeared at 1 h and gradually increased, indicating that Mn-iCOF could be cleared by the liver and kidney. As demonstrated in Figure 6D, after intravenous injection with the Mn-iCOF, the Mn content reached the maximum at 2 h in the liver, spleen, and kidney and gradually decreased with time prolongation.…”

Nanostructured Lipid Carrier Co-Loaded with Docetaxel and Magnetic Nanoparticles: Physicochemical Characterization and In Vitro Evaluation

“…NLC can also be co-loaded with imaging agents for combined therapeutic and diagnostic purposes, termed theranostics. Imaging modalities such as fluorescence imaging and magnetic resonance imaging (MRI) are helpful to visualize biological processes (e.g., apoptosis and cell trafficking), for monitoring responses to therapy and for diagnosing diseases [ 10 , 11 , 12 ]. The entrapment of imaging agents in its lipid core will enable signal enhancement in the targeted tissue after cell uptake.…”