title: 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 noninvasive 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 premanufactured liposomes were composed of DSPC/cholesterol/Gd-DOTA-DSPE/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 postinserted into the premanufactured liposomes. Doxorubicin could be effectively postloaded into the multifunctional liposomes. The multifunctional doxorubicin-liposomes could also be stably radiolabeled with (99m)Tc or (64)Cu 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 noninvasive multimodality NIR fluorescent, MR, SPECT, and PET imaging of their in vivo behavior and capitalizing on the inherent advantages of each modality.
authors.affiliation: Department of Radiology and ‡Department of Otolaryngology - Head and Neck Surgery, University of Texas Health Science Center at San Antonio , San Antonio, Texas.
authors.forename: Shihong
authors.initials: S
authors.lastname: Li
authors.forename: Beth
authors.initials: B
authors.lastname: Goins
authors.forename: Lujun
authors.initials: L
authors.lastname: Zhang
authors.forename: Ande
authors.initials: A
authors.lastname: Bao
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000188:drug therapy; D003301:Copper Radioisotopes / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016503:Drug Delivery Systems; D005456:Fluorescent Dyes / Q000737:chemistry; D006258:Head and Neck Neoplasms / Q000175:diagnosis* / Q000188:drug therapy; D006571:Heterocyclic Compounds / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D061848:Optical Imaging; D009942:Organometallic Compounds / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage; D049268:Positron-Emission Tomography; D051381:Rats; D011923:Rats, Nude; D000077195:Squamous Cell Carcinoma of Head and Neck; D013667:Technetium / Q000737:chemistry; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D000903:Antibiotics, Antineoplastic; D003301:Copper Radioisotopes; D005456:Fluorescent Dyes; D006571:Heterocyclic Compounds; D008081:Liposomes; D009942:Organometallic Compounds; D010714:Phosphatidylethanolamines; C506643:liposomal doxorubicin; C002449:glycerophosphoethanolamine; D011092:Polyethylene Glycols; D013667:Technetium; D004317:Doxorubicin; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate