Co‐encapsulation of anti‐<i>BCR‐ABL</i> siRNA and imatinib mesylate in transferrin receptor‐targeted sterically stabilized liposomes for chronic myeloid leukemia treatment

Mendonça, Liliana; Moreira, João Nuno; Lima, Maria C. Pedroso de; Simões, Sérgio

doi:10.1002/bit.22858

Cited by 48 publications

(24 citation statements)

References 46 publications

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“…[39][40][41] Since imatinib has four protonizable amine functional groups and is uncharged as a neutral form at physiological pH, it is possible to perform an active entrapment approach, in which imatinib can cross the liposomal membrane and be entrapped in the liposomal lumen due to its protonation at acidic pH values. Active drug loading is known for enhanced in vitro and in vivo drug retention when compared to passive methods.…”

mentioning

confidence: 99%

Folate receptor-targeted liposomes enhanced the antitumor potency of imatinib through the combination of active targeting and molecular targeting

Ye¹,

Zhang²,

Tan³

et al. 2014

IJN

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Purpose Imatinib inhibits platelet-derived growth factor receptor (PDGFR), and evidence shows that PDGFR participates in the development and progression of cervical cancer. Although imatinib has exhibited preclinical activity against cervical cancer, only minimal clinical therapeutic efficacy was observed. This poor therapeutic efficacy may be due to insufficient drug delivery to the tumor cells and plasma protein binding. Therefore, the purpose of this study was to explore a novel folate receptor (FR)-targeted delivery system via imatinib-loaded liposomes to enhance drug delivery to tumor cells and to reduce plasma protein binding. Methods Imatinib was remote-loaded into FR-targeted liposomes which were prepared by thin film hydration followed by polycarbonate membrane extrusion. Encapsulation efficiency, mean size diameter, and drug retention were characterized and cellular uptake, cell cytotoxicity, and cell apoptosis on cervical cancer HeLa cells were evaluated. Comparative pharmacokinetic studies were also carried out with FR-targeted imatinib liposomes, simple imatinib liposomes, and free imatinib. Results High encapsulation efficiency (>90%), appropriate mean particle size (143.5 nm), and zeta potential (−15.97 mV) were obtained for FR-targeted imatinib liposomes. The drug release profile showed minimal imatinib leakage (<5%) in phosphate-buffered saline (PBS) at pH =7.4 within 72 hours of incubation, while more leakage (>25%) was observed in PBS at pH =5.5. This indicates that these liposomes possess a certain degree of pH sensitivity. Cytotoxicity assays demonstrated that the FR-targeted imatinib liposomes promoted a six-fold IC 50 reduction on the non-targeted imatinib liposomes from 910 to 150 μM. In addition, FR-targeted imatinib liposomes enhanced HeLa cell apoptosis in vitro compared to the non-targeted imatinib liposomes. Pharmacokinetic parameters indicated that both targeted and non-targeted liposomes exhibited long circulation properties in Kunming mice. Conclusion These findings indicate that the nano-sized FR-targeted PDGFR antagonist imatinib liposomes may constitute a promising strategy in cervical cancer therapy through the combination of active targeting and molecular targeting.

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confidence: 99%

Folate receptor-targeted liposomes enhanced the antitumor potency of imatinib through the combination of active targeting and molecular targeting

Ye¹,

Zhang²,

Tan³

et al. 2014

IJN

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“…BCR-ABL encodes the BCR-ABL protein, a constitutively active tyrosine kinase, responsible for malignant transformation. Therefore, silencing BCR-ABL is an approach that is being explored for CML treatment [56][57][58]. Our siRNA-lipoplexes were found to efficiently downregulate BCR-ABL gene expression (Fig.…”

Section: Discussionmentioning

confidence: 89%

Stealth monoolein-based nanocarriers for delivery of siRNA to cancer cells

et al. 2015

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This work describes two stealth functionalization strategies for the stabilization of the previously validated dioctadecyldimethylammonium bromide (DODAB):monoolein (MO) siRNA-lipoplexes. These nanocarriers are capable of efficiently incorporating and delivering siRNA molecules to cells in order to silence genes whose expression is implicated in a pathological condition. The main objective was to functionalize these nanocarriers with a coating conferring protection to siRNA in blood without compromising its efficient delivery to cancer cells, validating the potential of DODAB:MO (2:1) siRNA-lipoplexes as therapeutic vectors. We show that the stealth strategy is determinant to achieve a stable and efficient nanocarrier, and that DODAB:MO mixtures have a very promising potential for systemic siRNA delivery to leukemic cells.

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“…Furthermore, the use of siRNA to inhibit cancer-relevant molecular targets has been explored as a valuable strategy to enhance chemosensitivity of cancer cells [9,38,39].…”

Section: Discussionmentioning

confidence: 99%

Impact of anti-PLK1 siRNA-containing F3-targeted liposomes on the viability of both cancer and endothelial cells

Gomes‐da‐Silva

Ramalho

Lima

et al. 2013

European Journal of Pharmaceutics and Biopharmaceutics

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a b s t r a c tWe have previously described the development of novel sterically stabilized F3-targeted pH-sensitive liposomes, which exhibited the ability to target both cancer and endothelial cells. Herein, the therapeutic potential of those liposomes was assessed upon encapsulation of a siRNA against a well-validated molecular target, PLK1.Treatment of prostate cancer (PC3) and angiogenic endothelial (HMEC-1) cells with F3-targeted liposomes containing anti-PLK1 siRNA resulted in a significant decrease in cell viability, which was mediated by a marked PLK1 silencing, both at the mRNA and protein levels. Furthermore, pre-treatment of PC3 cells with F3-targeted liposomes containing anti-PLK1 siRNA enabled a 3-fold reduction of paclitaxel IC 50 and a 2.5-fold augment of the percentage of cancer cells in G2/mitosis arrest, which ultimately culminated in cell death.Overall, the F3-targeted nanocarrier containing an anti-PLK1 siRNA might constitute a valuable system for prostate cancer treatment, either applied in a single schedule or combined with conventional chemotherapy.

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Co‐encapsulation of anti‐BCR‐ABL siRNA and imatinib mesylate in transferrin receptor‐targeted sterically stabilized liposomes for chronic myeloid leukemia treatment

Cited by 48 publications

References 46 publications

Folate receptor-targeted liposomes enhanced the antitumor potency of imatinib through the combination of active targeting and molecular targeting

Folate receptor-targeted liposomes enhanced the antitumor potency of imatinib through the combination of active targeting and molecular targeting

Stealth monoolein-based nanocarriers for delivery of siRNA to cancer cells

Impact of anti-PLK1 siRNA-containing F3-targeted liposomes on the viability of both cancer and endothelial cells

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