ABSTRACT
Photothermal therapy (PTT) is a promising cancer therapeutic approach due to its spatial selectivity and high potency. Indocyanine green (ICG) has been considered a biocompatible PTT agent. However, ICG has several challenges to hinder its clinical use including rapid blood clearance and instability to heat, light, and solvent, leading to a loss of photoactivation property and PTT efficacy. Herein, we leveraged stabilizing components, methyl-ß-cyclodextrin and liposomes, in one nanoplatform (ICD lipo) to enhance ICG stability and the photothermal therapeutic effect against cancer. Compared to ICG, ICD lipo displayed a 4.8-fold reduction in degradation in PBS solvent after 30 days and a 3.4-fold reduction in photobleaching after near-infrared laser irradiation. Moreover, in tumor-bearing mice, ICD lipo presented a 2.7-fold increase in tumor targetability and inhibited tumor growth 9.6 times more effectively than did ICG without any serious toxicity. We believe that ICD lipo could be a potential PTT agent for cancer therapeutics.
Subject(s)
Indocyanine Green , Liposomes , Photothermal Therapy , Indocyanine Green/chemistry , Indocyanine Green/pharmacology , Indocyanine Green/therapeutic use , Animals , Mice , Liposomes/chemistry , Humans , beta-Cyclodextrins/chemistry , Cell Line, Tumor , Neoplasms/therapy , Neoplasms/drug therapy , Neoplasms/pathology , Female , Mice, Inbred BALB C , PhototherapyABSTRACT
Nanoparticles are primarily taken up by immune cells after systemic administration. Thus, they are considered an ideal drug delivery vehicle for immunomodulation. Because the spleen is the largest lymphatic organ and regulates the systemic immune system, there have been studies to develop spleen targeting nanoparticles for immunomodulation of cancer and immunological disorders. Inflammatory bowel disease (IBD) includes disorders involving chronic inflammation in the gastrointestinal tract and is considered incurable despite a variety of treatment options. Hydrogen sulfide (H2S) is one of the gasotransmitters that carries out anti-inflammatory functions and has shown promising immunomodulatory effects in various inflammatory diseases including IBD. Herein, we developed a delicately tuned H2S donor delivering liposome for spleen targeting (ST-H2S lipo) and studied its therapeutic effects in a dextran sulfate sodium (DSS) induced colitis model. We identified the ideal PEG type and ratio of liposome for a high stability, loading efficiency, and spleen targeting effect. In the treatment of the DSS-induced colitis model, we found that ST-H2S lipo and conventional long-circulating liposomes loaded with H2S donors (LC-H2S lipo) reduced the severity of colitis, whereas unloaded H2S donors did not. Furthermore, the therapeutic effect of ST-H2S lipo was superior to that of LC-H2S lipo due to its better systemic immunomodulatory effect than that of LC-H2S lipo. Our findings demonstrate that spleen targeting H2S lipo may have therapeutic potential for IBD.
Subject(s)
Colitis , Inflammatory Bowel Diseases , Humans , Liposomes/adverse effects , Spleen , Inflammatory Bowel Diseases/drug therapy , Colitis/drug therapy , ImmunomodulationABSTRACT
Extracellular vesicles (EVs) have been found to be effective therapeutic drug delivery vehicles in a wide range of human diseases, including cancer and neurodegenerative diseases. Proinflammatory (M1) macrophages can modulate the suppressive immune environment of tumor tissues to be more inflammatory and have been considered as candidates for cancer immunotherapy. Furthermore, macrophage-derived exosome-mimetic nanovesicles (MNVs) could effectively induce antitumor response and enhance the efficacy of immune checkpoint inhibitors in a recent paper. However, multiple studies indicate that EVs were rapidly cleared by the reticuloendothelial system, and therefore, their tumor targeting efficiencies were limited. Herein, we developed a simple surface modification method of MNVs using polyethylene glycol (PEG) to enhance the in vivo tumor targeting efficiency. PEG-MNVs had 7-fold higher blood circulation than bare MNVs in the animal tumor model. Also, MNVs had a 25-fold higher protein amount than exosomes. Overall, the nanovesicle preparation strategies presented in this study may expedite the clinical translation of EV-based therapeutics in various diseases.
