Homing of ICG-loaded liposome inlaid with tumor cellular membrane to the homologous xenografts glioma eradicates the primary focus and prevents lung metastases through phototherapy

Abstract

Currently, phototherapy initiated by local irradiation with a near-infrared (NIR) laser has emerged as a promising strategy for cancer treatment owing to its low toxicity. However, a key problem for effective phototherapy is how to specifically deliver a sufficient dose of photosensitizers to a tumor focus. Herein, indocyanine green (ICG), a United States Food and Drug Administration (US FDA)-approved photosensitizer, was first encapsulated in an inner aqueous compartment of liposome (ICG-LIP) to improve its stability. Thereafter, tumor cell membranes were isolated from native glioma cells and subsequently inlaid in the bilayer lipid membrane of ICG-LIP to construct cell-like liposomes (ICG-MCLs). ICG was easily encapsulated into the ICG-MCLs with a very high encapsulation efficiency, reaching 78.01 ± 0.72% and its concentration in the final formulation reached 200 μg mL-1. The ICG-MCLs displayed a spherical morphology with a hydrodynamic diameter (Dh) of 115.0 ± 0.5 nm, a PDI of 0.14, and a zeta potential of -11.2 ± 0.9 mV. Moreover, ICG-MCLs exhibited a good stability in terms of particle size and significantly improved the chemical stability of ICG in pH 7.4 PBS at 37 °C. In addition, the temperature of the ICG-MCLs rapidly increased to 63 °C after 10 min irradiation and this was maintained for a longer time. Owing to the cancer cell membrane associated protein, the ICG-MCLs were specifically internalized by homogenous glioma C6 cells in vitro, which resulted in the strong red fluorescence of ICG in cytoplasm. Moreover, in vivo imaging showed that the ICG-MCLs were effectively homed to the tumor site of C6 glioma-bearing Xenograft nude mice through vein injection, which resulted in the temperature of the tumor site rapidly rising, allowing the killing of tumor cells after local NIR irradiation. After treatment with the ICG-MCLs, the primary tumor focus was completely eradicated and lung metastases were effectively inhibited. In conclusion, liposomes inlaid with tumor cellular membranes may serve as an excellent nanoplatform for homologous-targeting phototherapy using ICG.

Targeting Fluorescence Imaging of RGD-Modified Indocyanine Green Micelles on Gastric Cancer

“…The LD and EE are crucial properties in drug delivery. In our study, the LD and EE of ICG were 11.4 and 34.2%, which were lower compared with previous studies (Xu et al, 2018). Similar results of micelles with or without RGD modifications were obtained.…”

Cancer‐Cell‐Derived Hybrid Vesicles from MCF‐7 and HeLa Cells for Dual‐Homotypic Targeting of Anticancer Drugs

“…As illustrated in Figure 1 a, two types of VEs, MCF‐7 VEs and HeLa VEs, were prepared by sonication and sequential centrifugation from MCF‐7 and HeLa cells, respectively. [ 18,19 ] After incubating MCF‐7 VEs with HeLa VEs in the presence of saponin at 37 °C, the hybrid VEs were prepared via vesicular fusion. [ 20 ] We hypothesized that the resultant hybrid VEs are endowed with the properties of each membrane for the simultaneous delivery to two types of cancer cells via homotypic interactions (Figure 1b).…”

“…Bio‐TEM images revealed cup‐shaped VEs and a smaller size than that detected by DLS owing to the dehydration of the samples, as observed in a previous study. [ 18 ] Figure 2b indicates that the surface charges of MCF‐7, HeLa, and hybrid VEs under physiological conditions were −29.2 ± 1.8, −28.0 ± 0.4, and −27.8 ± 1.9 mV, respectively. This result is consistent with those of previous studies.…”

“…[ 18,21,22 ] Proteins in cell lysates from MCF‐7 and HeLa cells, MCF‐7 VEs, HeLa VEs, and hybrid VEs were examined by Coomassie staining after sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS‐PAGE) (Figure S1a, Supporting Information), according to a previous study. [ 18 ] As a result, we found that the protein bands for VE were slightly different from those observed for cell lysates, probably owing to the presence of intracellular proteins in cell lysates. However, hybridization was not verified by Coomassie staining of proteins because of the similar protein migration patterns of MCF‐7 and HeLa VEs.…”

“…[ 16,17 ] Recently, hybrid VEs comprising two types of cell‐derived VEs (e.g., red blood cell (RBC)–B16‐F10 hybrid membrane) and synthetic liposome/cell‐derived membranes (e.g., C6 glioma cell membranes/liposomes) have been reported for homotypic targeting and long circulation. [ 10,18 ] However, hybrid VEs comprising two types of cancer cells for dual targeting to two types of tumors have not yet been reported.…”