Preparation, characterization, in vitro and in vivo anti-tumor effect of thalidomide nanoparticles on lung cancer

Chen, Long Xia; Ni, Xiao; Zhang, Heng; Wu, Min; Liu, Jing; Xu, Shan; Yang, Ling; Shao, Fu; Wu, Jingbo

doi:10.2147/ijn.s159327

Cited by 19 publications

(9 citation statements)

References 42 publications

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“…Recently, nanoparticles have attracted increasing attention for the dramatic enhanced anticancer effects and reduced systemic toxicity in chemotherapy. 16 It has been reported that encapsulation of anticancer drugs by nanoparticles could efficiently deliver drugs to tumor sites through an EPR effect and superior pharmacokinetics profiles in vivo, resulting in prolonged drug circulation and reduced systemic toxicity in vivo. 17 MPEG-PLA nanoparticles show high EE, stability and low clearance, which make it as a promising delivery tool for chemotherapeutic drugs.…”

Section: Mpeg-pla Nanoparticles Encapsulated Cq-and Dox-induced Enhanmentioning

confidence: 99%

Encapsulation of chloroquine and doxorubicin by MPEG-PLA to enhance anticancer effects by lysosomes inhibition in ovarian cancer

Shao¹,

Zhu²,

Lv³

et al. 2018

IJN

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PurposeAs the deadliest gynecological malignancy, ovarian cancer ranks as a major cause of disease-related deaths to women worldwide and is treated with transurethral resection or systemic chemotherapy. However, traditional chemotherapeutic drug in antitumor therapy has shown unavoidable limitations, such as poor curative effects, systemic toxicity and development of drug resistance, leading to failure of tumor inhibition and recurrence. This study aims to explore an innovative method to enhance the clinical efficiency of ovarian cancer.Materials and methodsUsing MTT assay, the cell viability was detected under different culture systems. Western blot was used to examine the expression of P-gp in doxorubicin-resistant and wild-type A2780/SKOV3 cells. We used confocal to examine the drug concentration under different culture conditions. Also, flow cytometry was used to detect the drug absorption at the determined time points under different culture systems. Using nude mice model, we evaluated the killing efficacy of chemotherapeutic drugs with or without nanoparticle encapsulation. ELISA was used to examine the levels of creatinine, alanine aminotransferase and aspartate aminotransferase in plasma.ResultsWe found that pretreatment of chloroquine (CQ) as chemosensitizer markedly enhanced the anticancer effects in ovarian cancer. We also provided evidence that CQ efficiently increase the pH value of lysosomes in tumor cells, leading to the reverse of drug sequestration induced by lysosomes. To further improve the pharmacokinetics profiles and avoid the systemic toxicity caused by chemotherapeutic agents, we encapsulated CQ and chemotherapeutic drugs by polymeric nanoparticles methoxy poly(ethylene glycol)-poly(l-lactic acid). Codelivery of CQ and chemotherapeutic agents by nanocarrier revealed enhanced anticancer effects compared with the free drug delivery by tail vein injection. More importantly, accumulated drugs, prolonged drug circulation and reduced organic damages were observed in nanoparticles delivery.ConclusionCodelivery of CQ and chemotherapeutic drugs by methoxy poly(ethylene glycol)-poly(l-lactic acid) could significantly improve the anticancer effects and might have important potency in clinical applications for ovarian cancer therapy.

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Section: Mpeg-pla Nanoparticles Encapsulated Cq-and Dox-induced Enhanmentioning

confidence: 99%

Encapsulation of chloroquine and doxorubicin by MPEG-PLA to enhance anticancer effects by lysosomes inhibition in ovarian cancer

Shao¹,

Zhu²,

Lv³

et al. 2018

IJN

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“…Additionally, CQ, with proven efficiency in preclinical studies, has been reported to present difficulties in passing through the cell membrane in the presence of acidic extracellular microenvironments, which is characteristic of tumors [ 9 , 11 ]. This problem could be overcome by the encapsulation of CQ using nanoparticles, an approach that has been demonstrated to increase not only the CQ antitumor effect but also the efficient delivery of drugs to tumor sites with superior pharmacokinetic profiles, prolonged drug circulation, and reduced systemic toxicity in vivo [ 15 , 16 , 82 , 83 , 84 ]. The encapsulation of CQ together with an NHEJ inhibitor could then be explored for the treatment of OC to recapitulate the efficacy of this combination shown in this work.…”

Section: Discussionmentioning

confidence: 99%

Chloroquine-Induced DNA Damage Synergizes with Nonhomologous End Joining Inhibition to Cause Ovarian Cancer Cell Cytotoxicity

Ovejero-Sánchez

Rubio-Heras

Peña

et al. 2022

IJMS

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Ovarian cancer (OC) is the most lethal gynecological malignancy; therefore, more effective treatments are urgently needed. We recently reported that chloroquine (CQ) increased reactive oxygen species (ROS) in OC cell lines (OCCLs), causing DNA double-strand breaks (DSBs). Here, we analyzed whether these lesions are repaired by nonhomologous end joining (NHEJ), one of the main pathways involved in DSB repair, and if the combination of CQ with NHEJ inhibitors (NHEJi) could be effective against OC. We found that NHEJ inhibition increased the persistence of γH2AX foci after CQ-induced DNA damage, revealing an essential role of this pathway in the repair of the lesions. NHEJi decreased the proliferation of OCCLs and a strong in vitro synergistic effect on apoptosis induction was observed when combined with CQ. This effect was largely abolished by the antioxidant N-Acetyl-L-cysteine, revealing the critical role of ROS and DSB generation in CQ/NHEJi-induced lethality. We also found that the NHEJ efficiency in OCCLs was not affected by treatment with Panobinostat, a pan-histone deacetylase inhibitor that also synergizes with CQ in OCCLs by impairing homologous recombination. Accordingly, the triple combination of CQ-NHEJi-Panobinostat exerted a stronger in vitro synergistic effect. Altogether, our data suggest that the combination of these drugs could represent new therapeutic strategies against OC.

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“…This information could be of paramount importance in clinical settings. Food intake delayed (T max ) but increased TAL absorption (C max and AUC), in line with the negligible hydrophilicity of the active compound [ 30 31 ]. Interestingly, the effect of food on TAL pharmacokinetics in humans are conflicting: some studies report no influences while others report minor effects on C max and AUC, with a significant delay to T max [ 2 28 ].…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of thalidomide in dogs: can feeding affect it? A preliminary study

et al. 2020

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Background Tumor-associated neoangiogenesis is a crucial target for antitumor therapies. Thalidomide (TAL) is a promising anti-neoangiogenetic drug that has recently been used in the treatment of several malignancies in dogs. Objectives The aim of the study was to assess the pharmacokinetics of TAL after single oral administration in dogs. Additionally, the influence of feeding on the pharmacokinetic profile of TAL in dogs has been preliminarily investigated. Methods Six healthy adult female Labradors were enrolled according to a randomized single-dose, 2-treatment, 2-phase, paired 2 × 2 cross-over study design. The dogs were administered a single 400 mg capsule of TAL in fasted and fed conditions. Blood was collected from 15 min to 48 h after dosing, and TAL quantified in plasma by a validated high-performance liquid chromatography method. The pharmacokinetics of TAL were analyzed using a non-compartmental approach. Results TAL concentration was quantifiable up to 10 h and 24 h after fasted and fed conditions, respectively. C max (fasted, 1.34 ± 0.12 µg/mL; fed, 2.47 ± 0.19 µg/mL) and T max (fasted, 3 h; fed, 10 h) differed substantially between the 2 groups. AUC and t 1/2 λz were significantly higher in fed (42.46 ± 6.64 mg × h/L; 17.14 ± 4.68 h) compared to fasted (12.38 ± 1.13 mg × h/L; 6.55 ± 1.25 h) dogs. The relative oral bioavailability of TAL for the fasted group was low (36.92% ± 3.28%). Conclusions Feeding affects the pharmacokinetics of oral TAL in dogs, showing a delayed, but higher absorption with different rate of elimination. These findings are of importance in clinical veterinary settings, and represent a starting point for further related studies.

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Preparation, characterization, in vitro and in vivo anti-tumor effect of thalidomide nanoparticles on lung cancer

Cited by 19 publications

References 42 publications

Encapsulation of chloroquine and doxorubicin by MPEG-PLA to enhance anticancer effects by lysosomes inhibition in ovarian cancer

Encapsulation of chloroquine and doxorubicin by MPEG-PLA to enhance anticancer effects by lysosomes inhibition in ovarian cancer

Chloroquine-Induced DNA Damage Synergizes with Nonhomologous End Joining Inhibition to Cause Ovarian Cancer Cell Cytotoxicity

Pharmacokinetics of thalidomide in dogs: can feeding affect it? A preliminary study

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