Novel Multifunctional Theranostic Liposome Drug Delivery System: Construction, Characterization, and Multimodality MR, Near-Infrared Fluorescent, and Nuclear Imaging

Abstract

Liposomes are effective lipid nanoparticle drug delivery systems, which can also be functionalized with non-invasive multimodality imaging agents with each modality providing distinct information and having synergistic advantages in diagnosis, monitoring of disease treatment, and evaluation of liposomal drug pharmacokinetics. We designed and constructed a multifunctional theranostic liposomal drug delivery system, which integrated multimodality magnetic resonance (MR), near-infrared (NIR) fluorescent and nuclear imaging of liposomal drug delivery, and therapy monitoring and prediction. The pre-manufactured liposomes were composed of DSPC/cholesterol/Gd-DOTADSPE/DOTA-DSPE with the molar ratio of 39:35:25:1 and having ammonium sulfate/pH gradient. A lipidized NIR fluorescent tracer, IRDye-DSPE, was effectively post-inserted into the pre-manufactured liposomes. Doxorubicin could be effectively post-loaded into the multifunctional liposomes. The multifunctional doxorubicin-liposomes could also be stably radiolabeled with 99mTc or 64Cu for single photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging, respectively. MR images displayed the high resolution micro-intratumoral distribution of the liposomes in squamous cell carcinoma of head and neck (SCCHN) tumor xenografts in nude rats after intratumoral injection. NIR fluorescent, SPECT and PET images also clearly showed either the high intratumoral retention or distribution of the multifunctional liposomes. This multifunctional drug carrying liposome system is promising for disease theranostics allowing non-invasive multimodality NIR fluorescent, MR, SPECT and PET imaging of their in vivo behavior and capitalizing on the inherent advantages of each modality.

Influence of PEGylation and RGD loading on the targeting properties of radiolabeled liposomal nanoparticles

“…40 On the other hand, PEGylation is advantageous when using LNPs in vivo as it prolongs their circulation time and reduces recognition by the mononuclear phagocyte system, giving the liposome sufficient time to arrive at its target. 41 This hypothesis was confirmed in the M21/M21-L tumor xenograft model. When injected into nude mice, blood levels of In-medRLP with no PEG building block were much lower than those of 111 In-medRLP with PEGylation.…”

Liposomes as nanomedical devices

“…These liposomes were applied in vivo to a squamous cell carcinoma of head and neck tumor xenograft in nude rats after intratumoral injection. 181 Muthu et al prepared tocopheryl polyethylene glycol 1000 succinate-coated theranostic liposomes containing Dox and quantum dots with and without targeting moieties. 182 Folic acid was used as the targeting probe to target folate receptors overexpressing MCF-7 breast cancer cell lines.…”

Dynamic imaging of PEGylated indocyanine green (ICG) liposomes within the tumor microenvironment using multi-spectral optoacoustic tomography (MSOT)

“…The need for baseline measurements makes long-term longitudinal studies impractical and sensitive to motion with time. The use of radiotracers for PET and SPECT imaging has been considered as a higher sensitivity alternative to MRI and CT [11,16]. Nuclear imaging however, suffers from low spatial resolution and the relatively short time-course allowed for imaging due to the energy-decaying radionuclides employed, in particular with 18 F nuclear tracers, although alternatives such as 89 Zc are explored as longer half-life alternatives.…”