Gefitinib-loaded DSPE-PEG2000 nanomicelles with CD133 aptamers target lung cancer stem cells

Abstract

BackgroundLung cancer stem cells (CSCs) are considered to be the seed of lung cancer, and CD133 is a marker of lung CSCs. Here, we developed gefitinib-loaded poly(ethylene glycol) 2000-distearoylphosphatidylethanolamine nanomicelles with CD133 aptamers (M-Gef-CD133) to eliminate CD133+ lung CSCs.MethodsM-Gef-CD133 was prepared using a lipid-film-based approach. The targeting and activity of M-Gef-CD133 towards lung CSCs were evaluated.ResultsM-Gef-CD133 were small (25 nm) and showed enhanced cytotoxic effect towards CD133+ lung CSCs compared with non-targeted M-Gef and gefitinib. Notably, M-Gef-CD133 could significantly reduce tumor sphere formation and the percentage of CD133+ lung CSCs, indicating that it possesses selective toxicity against CD133+ lung CSCs.ConclusionsThe interaction of CD133 aptamers and CD133 shows promise in the delivery of gefitinib to CD133+ lung CSCs, and M-Gef-CD133 represents a promising treatment to target lung CSCs.

Dual‑targeting nanomicelles with CD133 and CD44 aptamers for enhanced delivery of gefitinib to two populations of lung cancer‑initiating cells

“…In addition, CD133 + lung cancer cells have been indicated to highly express a variety of stemness genes (5,6). A previous study by our group also confirmed that CD133 + lung cancer cells expressed high levels of stemness genes and had increased tumorigenicity in mice compared with CD133-lung cancer cells, suggesting that CD133 + lung cancer cells exhibited lung cancer-initiating cell properties (7). However, tumors may consist of multiple genetically or phenotypically distinct types of cancer-initiating cells.…”

“…Polyethylene glycol 2000-distearoyl phosphatidylethanolamine (DSPE-PEG2000) nanomicelles are promising due to their particularly small size (~20 nm), good biocompatibility and superior penetration into solid tumors (14–16). In a previous study by our group, CD133 aptamer-conjugated gefitinib DSPE-PEG2000 nanomicelles (CD133-NM-Gef) were constructed to enhance the delivery of gefitinib into lung tumors (7). In the present study, to achieve simultaneous targeting of nanomicelles to CD44 + and CD133 + cancer cells, CD44 aptamers were further conjugated to CD133-NM-Gef to develop CD133 and CD44 aptamer-conjugated nanomicelles loaded with gefitinib (CD133/CD44-NM-Gef).…”

MicroRNA-128 suppresses paclitaxel-resistant lung cancer by inhibiting MUC1-C and BMI-1 in cancer stem cells

“…To determine the self-renewal ability of A549/PTX CD133 + cells and CD133 - cells, we performed sphere formation assays, which are performed to identify stem cells via their capacity of self-renewal and differentiation at the levels of single cells [ 28 ]. As shown in Figure 2A and 2B , the number and size of the spheres formed by CD133 + cells were significantly larger compared with those formed by CD133 - cells, indicating that A549/PTX CD133 + cells have a higher self-renewal capacity than CD133 - cells.…”

Recent advances in drug delivery systems for targeting cancer stem cells

“…In this respect, targeting CSCs based on their specific biomarkers is unquestionably a rational choice, and correspondingly, a great amount of biomarkers-mediated delivery carriers and systems have been developed and explored. Table 2 24 , 25 , 26 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 presents an overview of recent representative drug delivery carriers and systems. CD44 is one of the most famous surface markers related to CSCs, and HA is the main component of the extracellular matrix, especially as it is abundantly expressed in a wide variety of CSCs and has a high affinity for CD44 receptors and better biocompatibility than anti-CD44 antibody 91 .…”