ABSTRACT
Retinoblastoma (RB) is a malignant intraocular neoplasm that occurs in children. Diagnosis and therapy are frequently delayed, often leading to metastasis, which necessitates effective imaging and treatment. In recent years, the use of nanoplatforms allowing both imaging and targeted treatment has attracted much attention. Herein, we report a novel nanoplatform folate-receptor (FR) targeted laser-activatable liposome termed FA-DOX-ICG-PFP@Lip, which is loaded with doxorubicin (DOX)/indocyanine green (ICG) and liquid perfluoropentane (PFP) for photoacoustic/ultrasound (PA/US) dual-modal imaging-guided chemo/photothermal RB therapy. The dual-modal imaging capability, photothermal conversion under laser irradiation, biocompatibility, and antitumor ability of these liposomes were appraised. The multifunctional liposome showed a good tumor targeting ability and was efficacious as a dual-modality contrast agent both in vivo and in vitro. When laser-irradiated, the liposome converted light energy to heat. This action caused immediate destruction of tumor cells, while simultaneously initiating PFP phase transformation to release DOX, resulting in both photothermal and chemotherapeutic antitumor effects. Notably, the FA-DOX-ICG-PFP@Lip showed good biocompatibility and no systemic toxicity was observed after laser irradiation in RB tumor-bearing mice. Hence, the FA-DOX-ICG-PFP@Lip shows great promise for dual-modal imaging-guided chemo/photothermal therapy, and may have significant value for diagnosing and treating RB.
Subject(s)
Antibiotics, Antineoplastic/pharmacology , Doxorubicin/pharmacology , Liposomes/chemistry , Photothermal Therapy/methods , Retinal Neoplasms/pathology , Retinoblastoma/pathology , Animals , Antibiotics, Antineoplastic/administration & dosage , Cell Line, Tumor , Cell Survival/drug effects , Chemistry, Pharmaceutical , Coloring Agents/administration & dosage , Doxorubicin/administration & dosage , Drug Carriers/chemistry , Drug Liberation , Folic Acid Transporters/drug effects , Humans , Indocyanine Green/administration & dosage , Mice , Nanoparticles/chemistry , Particle Size , Photoacoustic Techniques/methods , Random Allocation , Surface Properties , Ultrasonography, Interventional/methods , Xenograft Model Antitumor AssaysABSTRACT
The feasibility of chitosan (CS) as a backbone for the design of (99m)Tc-labeled targeting agent was evaluated in this study. Chitosan-folate conjugate (CSFA) and chitosan-folate dithiocarbamate (CSFADTC) were synthesized, characterized and radiolabeled with (99m)Tc as model compounds for folate-receptor (FR) targeting. (99m)Tc-complexes were prepared with high radiochemical purity and high stability. The hydrophilicities of these (99m)Tc-complexes were determined by partition coefficient experiments. The results of biodistribution in normal mice showed that the folic-acid modified agents ((99m)Tc-CSFA and (99m)TcN-CSFADTC) had obviously higher uptake in FR-positive kidney and much lower liver and spleen uptakes than that of non-folic-acid modified (99m)Tc-agent, and the kidney uptakes of FA-modified agents could be blocked significantly by the corresponding cold ligand. Furthermore in vitro and in vivo specific studies will be done in cell line and tumor bearing mice to confirm the usefulness of this chitosan backbone for FR targeting agent design.
Subject(s)
Chitosan/chemistry , Folic Acid Transporters/drug effects , Folic Acid/chemistry , Organotechnetium Compounds/chemistry , Animals , Chitosan/pharmacokinetics , Chromatography, High Pressure Liquid , Mice , Mice, Nude , Radiometry , Spectrophotometry, Infrared , Spectrophotometry, Ultraviolet , Tissue DistributionABSTRACT
Within the broad spectrum of nanoparticulate carriers, polymeric and lipid-core micelles, liposomes, solid nanoparticles and many others have demonstrated great biological properties which make them excellent pharmaceutical delivery systems. In particular, micelles and liposomes have been shown to have good longevity in the blood that allows their accumulation in pathological areas with a compromised vasculature; can possess specific targeting to disease sites when various targeting ligands are attached to the surface of the nanocarriers or to surface-attached cell-penetrating molecules (like TAT peptide) to enhance intracellular penetration; possess stimulus-sensitivity allowing for drug release from the carriers under certain pathological conditions; and show contrast properties with carrier loading of various contrast materials that allow for direct carrier visualization in vivo. The engineering of "multifunctional pharmaceutical nanocarriers" based on the combination of several useful properties in the same system can significantly enhance the efficacy of many therapeutic and diagnostic protocols. This review considers the current status and next future directions in the emerging area of nanomedicine with particular attention to two lipid-based nanoparticulate systems: liposomes and micelles.