Dual 7-ethyl-10-hydroxycamptothecin conjugated phospholipid prodrug assembled liposomes with in vitro anticancer effects

Du, Yawei; Zhang, Wei; He, Ruiyu; Ismail, Muhammad; Ling, Longbing; Chen, Yao; Fu, Zuoling; Li, Xinsong

doi:10.1016/j.bmc.2017.04.025

Cited by 34 publications

(24 citation statements)

References 44 publications

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“…Colorectal cancer (CRC) is one of the major causes of cancer‐related morbidity worldwide . Irinotecan (Iri), a water‐soluble camptothecin, is one of the first‐line therapeutic agents for advanced or metastatic colorectal cancer . Irinotecan functions by avoiding religation of the DNA strand via forming a cleavable drug‐DNA‐topoisomerase I complex, thus causing lethal double‐strand DNA breakage and cell death .…”

Section: Introductionmentioning

confidence: 99%

pH‐Responsive PEG‐Shedding and Targeting Peptide‐Modified Nanoparticles for Dual‐Delivery of Irinotecan and microRNA to Enhance Tumor‐Specific Therapy

Juang¹,

Chang²,

Wang³

et al. 2019

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Irinotecan is one of the main chemotherapeutic agents for colorectal cancer (CRC). MicroRNA‐200 (miR‐200) has been reported to inhibit metastasis in cancer cells. Herein, pH‐sensitive and peptide‐modified liposomes and solid lipid nanoparticles (SLN) are designed for encapsulation of irinotecan and miR‐200, respectively. These peptides include one cell‐penetrating peptide, one ligand targeted to tumor neovasculature undergoing angiogenesis, and one mitochondria‐targeting peptide. The peptide‐modified nanoparticles are further coated with a pH‐sensitive PEG‐lipid derivative with an imine bond. These specially‐designed nanoparticles exhibit pH‐responsive release, internalization, and intracellular distribution in acidic pH of colon cancer HCT116 cells. These nanoparticles display low toxicity to blood and noncancerous intestinal cells. Delivery of miR‐200 by SLN further increases the cytotoxicity of irinotecan‐loaded liposomes against CRC cells by triggering apoptosis and suppressing RAS/β‐catenin/ZEB/multiple drug resistance (MDR) pathways. Using CRC‐bearing mice, the in vivo results further indicate that irinotecan and miR‐200 in pH‐responsive targeting nanoparticles exhibit positive therapeutic outcomes by inhibiting colorectal tumor growth and reducing systemic toxicity. Overall, successful delivery of miR and chemotherapy by multifunctional nanoparticles may modulate β‐catenin/MDR/apoptosis/metastasis signaling pathways and induce programmed cancer cell death. Thus, these pH‐responsive targeting nanoparticles may provide a potential regimen for effective treatment of colorectal cancer.

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Section: Introductionmentioning

confidence: 99%

pH‐Responsive PEG‐Shedding and Targeting Peptide‐Modified Nanoparticles for Dual‐Delivery of Irinotecan and microRNA to Enhance Tumor‐Specific Therapy

Juang¹,

Chang²,

Wang³

et al. 2019

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117

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“…19,20 The low lipid solubility of SN38 limits its loading efficiency into liposomes. 3,21 In contrast, TAT-PEG-SN38 can be dissolved in ethanol along with lipids to form liposomes. Furthermore, TAT was used to enhance the cell penetrating ability of SN38.…”

Section: Results and Discussion Synthesis Of Sn38 Prodrugmentioning

confidence: 99%

“…The xenografts were established by injecting tumor cells on the right backside of nude mice. When the tumor volume reached approximately 120 mm 3 , nude mice were randomly separated into 6 groups. The mice received a single dose of saline, CPT-11, L-P/siRNA, L-SN38/P/siRNA, Tf-L-SN38/P/siRNA, or Tf-L-SN38 (5 mg/ kg SN38-equivalent dose, 2.5 mg/kg of siRNA) through intravenous injection every 3 days for 5 total treatments.…”

Section: Antitumor Activity Evaluation and In Vivo Distributionmentioning

confidence: 99%

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Liposomal codelivery of an SN38 prodrug and a survivin siRNA for tumor therapy

Bi¹,

Lee²,

Wang³

et al. 2018

IJN

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PurposeA liposome-based siRNA–drug combination was evaluated as a potential therapeutic strategy to improve the curative effect.MethodsA topoisomerase inhibitor SN38 prodrug was combined with a survivin siRNA through codelivery using transferrin (Tf)-L-SN38/P/siRNA. In this combination, SN38 was conjugated to the cell penetrating peptide TAT through a polyethylene glycol (PEG) linker to synthesize TAT-PEG-SN38. The amphiphilic TAT-PEG-SN38 was used as an ingredient of liposomes to improve the cellular uptake. Protamine was added to form an electrostatic complex with siRNA in the core of the liposomes. Tf was introduced to enable tumor cell targeting of liposomes (Tf-L-SN38/P/siRNA).ResultsTf-L-SN38/P/siRNA exhibited a particle size of 148 nm and a ζ-potential of +7.8 mV. The cellular uptake and antitumor activity were dependent on Tf receptor targeting, TAT-PEG-SN38, and siRNA codelivery. Tf-L-SN38/P/siRNA was shown to be considerably more effective than liposomes carrying individual components. This combination induced potent tumor inhibition (76.8%) in HeLa cell xenograft tumor-bearing nude mice.ConclusionThese data indicated that Tf-L-SN38/P/siRNA was an effective system for codelivery of SN38 and a survivin siRNA and that its therapeutic potential deserved further evaluation.

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“…13 Liposome-encapsulated (LE) SN38 uses a liposomal formulation to carry SN38, and as of 2016 a Phase II trial was studying how well liposomal SN38 works in the treatment of metastatic colorectal cancer. 14 Various carriers have also been investigated, including such polymers as polylactide-co-glycolic acid nanoparticles, 15 poly-hydroxypropyl methacrylamide, 16 chitosan, 17 a polymer decorated with hyaluronic acid, 18 a conjugated phospholipid, 19 dextran, 20 and a conjugated antibody. 21 Moreover, immunomedicine has brought precise and individual therapies in recent decades.…”

Section: Introductionmentioning

confidence: 99%

SN38-loaded <100 nm targeted liposomes for improving poor solubility and minimizing burst release and toxicity: in vitro and in vivo study

Fang

Chuang

et al. 2018

IJN

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BackgroundSN38 (7-ethyl-10-hydroxycamptothecin) is a camptothecin derivative acts against various tumors. However, SN38 is hydrolyzed in the physiological environment (pH 7.4), and this instability interferes with its potential therapeutic effect. Our objective was to investigate SN38-loaded liposomes to overcome the poor solubility of SN38 and its biodistribution, which further diminish its toxicity.Materials and methodsThe sub-100 nm targeted liposomes was employed to deliver SN-38 and evaluate the characterization, release behaviors, cytotoxicity, in vivo pharmacokinetics and biochemical assay.ResultsThe SN38-loaded targeted liposomes consisted of small (100.49 nm) spherical nanoparticles with negative charge (−37.93 mV) and high entrapment efficiency (92.47%). The release behavior of the SN38-loaded targeted liposomes was fitted with Higuchi kinetics (R2=0.9860). Free SN38 presented initial burst release. The IC50 for the SN38-loaded targeted liposomes (0.11 μM) was significantly lower than for the SN38 solution (0.37 μM) in the MCF7 cell line (P<0.01). Confocal laser scanning microscopy also confirmed highly efficient accumulation in the MCF7 cells. Pharmacokinetics demonstrated that the SN38-loaded targeted liposomes had a slightly increased half-life and mean residence time and decreased area under the concentration–time curve and maximum concentration. The results suggested that retention was achieved while the exposure of SN38 was significantly decreased. A noninvasive in vivo imaging system also showed that the targeted liposomes selectively targeted MCF7 tumors. In vivo toxicity data demonstrated that the decrease in platelets was significantly improved by SN38-loaded targeted liposomes, and diarrhea was not observed in BALB/c mice.ConclusionIn summary, SN38-loaded targeted liposomes could be a good candidate for application in human breast cancer.

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Dual 7-ethyl-10-hydroxycamptothecin conjugated phospholipid prodrug assembled liposomes with in vitro anticancer effects

Cited by 34 publications

References 44 publications

pH‐Responsive PEG‐Shedding and Targeting Peptide‐Modified Nanoparticles for Dual‐Delivery of Irinotecan and microRNA to Enhance Tumor‐Specific Therapy

pH‐Responsive PEG‐Shedding and Targeting Peptide‐Modified Nanoparticles for Dual‐Delivery of Irinotecan and microRNA to Enhance Tumor‐Specific Therapy

Liposomal codelivery of an SN38 prodrug and a survivin siRNA for tumor therapy

SN38-loaded <100 nm targeted liposomes for improving poor solubility and minimizing burst release and toxicity: in vitro and in vivo study

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Dual 7-ethyl-10-hydroxycamptothecin conjugated phospholipid prodrug assembled liposomes with in vitro anticancer effects

Cited by 34 publications

References 44 publications

pH‐Responsive PEG‐Shedding and Targeting Peptide‐Modified Nanoparticles for Dual‐Delivery of Irinotecan and microRNA to Enhance Tumor‐Specific Therapy

pH‐Responsive PEG‐Shedding and Targeting Peptide‐Modified Nanoparticles for Dual‐Delivery of Irinotecan and microRNA to Enhance Tumor‐Specific Therapy

Liposomal codelivery of an SN38 prodrug and a survivin siRNA for tumor therapy

SN38-loaded &lt;100 nm targeted liposomes for improving poor solubility and minimizing burst release and toxicity: in vitro and in vivo study

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SN38-loaded <100 nm targeted liposomes for improving poor solubility and minimizing burst release and toxicity: in vitro and in vivo study