Thiolated chitosan-modified PLA-PCL-TPGS nanoparticles for oral chemotherapy of lung cancer

Jiang, Liqin; Li, Xuemin; Liu, Lingrong; Zhang, Qiqing

doi:10.1186/1556-276x-8-66

Cited by 81 publications

(41 citation statements)

References 43 publications

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“…Previous clinical studies have shown that drug-loaded nanoparticles may be administered orally or injected. 22,23 Nanoparticles modified by thiolated chitosan can enhance cellular uptake and cytotoxicity, and have the potential for oral administration in the treatment of cancer. 22 On the other hand, the injectable form can be tailored to control drug release and thereby increase selective cell targeting, cell uptake, drug solubility, and circulation time.…”

Section: Discussionmentioning

confidence: 99%

“…22,23 Nanoparticles modified by thiolated chitosan can enhance cellular uptake and cytotoxicity, and have the potential for oral administration in the treatment of cancer. 22 On the other hand, the injectable form can be tailored to control drug release and thereby increase selective cell targeting, cell uptake, drug solubility, and circulation time. 23 As a molecularly targeted anticancer drug, sorafenib requires oral administration at present.…”

Section: Discussionmentioning

confidence: 99%

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Targeted therapy for human hepatic carcinoma cells using folate-functionalized polymeric micelles loaded with superparamagnetic iron oxide and sorafenib in vitro

Zhang¹,

Gong²,

Zhang³

et al. 2013

IJN

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Background:The purpose of this study was to evaluate the inhibitory effect of targeted folatefunctionalized micelles containing superparamagnetic iron oxide nanoparticles (SPIONs) and sorafenib on human hepatic carcinoma (HepG2) cells in vitro, and to observe the feasibility of surveillance of this targeting therapeutic effect by magnetic resonance imaging. Methods: Sorafenib and SPIONs were loaded into polymeric micelles. The targeted nanocarrier was synthesized by functionalizing the micelles with folate. Folate-free micelles loaded with sorafenib and SPIONs were used as control (nontargeted) micelles. Uptake of the nanocarrier by cells was assessed using Prussian blue staining after 1 hour of incubation with the polymeric micelles. The inhibitory effect of the targeted micelles on HepG2 cell proliferation at various concentrations of sorafenib was assessed in vitro using the methyl thiazolyl tetrazolium (MTT) assay and apoptotic analysis using flow cytometry. Magnetic resonance imaging using a clinical 1.5 T scanner was performed to detect changes in the signal intensity of cells after incubation with the targeted micelles. Results: Prussian blue staining showed significantly more intracellular SPIONs in cells incubated with the targeted micelles than those incubated with nontargeted micelles. The MTT assay showed that the average inhibitory ratio in the targeted group was significantly higher than that in the nontargeted group (38.13% versus 22.54%, P = 0.028). The mean apoptotic rate in the targeted cells, nontargeted cells, and untreated cells was 17.01%, 11.04%, and 7.89%, respectively. The apoptotic rate in the targeted cells was significantly higher than that in the nontargeted cells (P = 0.043). The T2 signal intensity on magnetic resonance imaging of cells treated with the targeted micelles decreased significantly with increasing concentrations of sorafenib in the cell culture medium, but there was no obvious decrease in signal intensity in cells treated with the nontargeted micelles. Conclusion: Folate-functionalized polymeric micelles loaded with SPIONs and sorafenib inhibited proliferation and induced apoptosis of HepG2 cells in vitro. The inhibitory events caused by targeted micelles can be monitored using clinical magnetic resonance.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Targeted therapy for human hepatic carcinoma cells using folate-functionalized polymeric micelles loaded with superparamagnetic iron oxide and sorafenib in vitro

Zhang¹,

Gong²,

Zhang³

et al. 2013

IJN

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“…22,23 In addition, TPGS has been reported to efficiently inhibit the growth of human lung cancer cells both in vivo and in vitro. 24 Furthermore, TPGS produces synergistic growth inhibition effects upon combination with other anticancer drugs due to its ability to induce apoptosis in tumor cells. 25 Although there have been many HA-based PNs exploited for drug delivery, this is the first report on the formulation of a multifunctional drug delivery system based on HA block copolymer and TPGS.…”

Section: Abbad Et Almentioning

confidence: 99%

“…The synergistic antitumor activity of TPGS in the presence of MH is due to its ability to induce ROS-generation and apoptosis. 54,55 Besides the two above reasons, another factor contributing to the improved cytotoxicity of MH-MNs over MH-PNs and free MH is the ability of both TPGS and MH to inhibit the P-gp protein expressed in A549 cells and reduce drug efflux. [56][57][58] cellular uptake HA-PBCA forms a core-shell structure block copolymer that can self-assemble into polymeric micelles or nanoparticles.…”

mentioning

confidence: 99%

Preparation, in vitro and in vivo evaluation of polymeric nanoparticles based on hyaluronic acid-poly(butyl cyanoacrylate) and D-alpha-tocopheryl polyethylene glycol 1000 succinate for tumor-targeted delivery of morin hydrate

Abbad¹,

Wang²,

Waddad³

et al. 2015

IJN

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Herein, we describe the preparation of a targeted cellular delivery system for morin hydrate (MH), based on a low-molecular-weight hyaluronic acid-poly(butyl cyanoacrylate) (HA-PBCA) block copolymer. In order to enhance the therapeutic effect of MH, D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) was mixed with HA-PBCA during the preparation process. The MH-loaded HA-PBCA “plain” nanoparticle (MH-PNs) and HA-PBCA/TPGS “mixed” nanoparticles (MH-MNs) were concomitantly characterized in terms of loading efficiency, particle size, zeta potential, critical aggregation concentration, and morphology. The obtained MH-PNs and MH-MNs exhibited a spherical morphology with a negative zeta potential and a particle size less than 200 nm, favorable for drug targeting. Remarkably, the addition of TPGS resulted in about 1.6-fold increase in drug-loading. The in vitro cell viability experiment revealed that MH-MNs enhanced the cytotoxicity of MH in A549 cells compared with MH solution and MH-PNs. Furthermore, blank MNs containing TPGS exhibited selective cytotoxic effects against cancer cells without diminishing the viability of normal cells. In addition, the cellular uptake study indicated that MNs resulted in 2.28-fold higher cellular uptake than that of PNs, in A549 cells. The CD44 receptor competitive inhibition and the internalization pathway studies suggested that the internalization mechanism of the nanoparticles was mediated mainly by the CD44 receptors through a clathrin-dependent endocytic pathway. More importantly, MH-MNs exhibited a higher in vivo antitumor potency and induced more tumor cell apoptosis than did MH-PNs, following intravenous administration to S180 tumor-bearing mice. Overall, the results imply that the developed nanoparticles are promising vehicles for the targeted delivery of lipophilic anticancer drugs.

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“…The most commonly used polymers used in lung cancer nanotherapeutics include polylactic acid (PLA) [165][166][167], poly(lactide-co-glycoside) (PLGA) [168][169][170], poly(ethylene glycol) (PEG) [171][172][173][174][175][176], poly(ethyleneimine) (PEI) [177][178][179][180][181], chitosan [182][183][184][185][186], and gelatin [187][188][189][190]. Nguyen et al developed conjugates that coupled cell penetrating peptides (CPP) to PEI, through a PEG linker.…”

Section: Organic Nanoparticles For Lung Cancermentioning

confidence: 99%

Study of novel nanoparticle transport and drug release for cancer treatment.

Gene¹

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Nano-scale particles sized 10-400 nm administered systemically preferentially extravasate from tumor vasculature due to the enhanced permeability and retention effect. Therapeutic success remains elusive, however, because of inhomogeneous particle distribution within tumor tissue. Insufficient tumor vascularization limits particle transport and also results in avascular hypoxic regions with non-proliferating cells, which can regenerate tissue after nanoparticle-delivered cytotoxicity or thermal ablation. In this study, gold nanoparticles were functionalized with phosphatidylcholine (two-layer) or phosphatidylcholine and HDL (three-layer) in the formation of "layered" nanoparticles. The diffusivity of both two-and three layered colloidal gold nanoparticles and silica gold nanoshells were examined in 3D cell cultures. Both two-and three layered nanoparticles showed enhanced diffusivity in comparison to previously developed PEGylated nanoparticles. As the two layer nanoparticles displayed enhanced diffusivity in comparison to three layer nanoparticles, the two layered nanoparticles were further examined in vivo using mice implanted with orthotopic pancreatic adenocarcinomas. The two layer colloidal gold nanoparticles showed enhanced diffusivity in comparison to silica gold nanoshells in vivo, suggesting that smaller nanoparticles were able to localize and diffuse from vasculature better than larger nanoparticles. Overall accumulation of solid gold nanoparticle accumulated in the tumor and filtering organs (liver and spleen) was 2X higher than silica gold nanoshells. Thus, two layer colloidal gold nanoparticles were loaded with cisplatin or paclitaxel to determine optimal drug release kinetics. Drug release from paclitaxel-loaded nanoparticles displayed a slower release while cisplatin-loaded nanoparticles experienced an initial burst of drug release followed by a slower release of remaining drug. Lastly, drug-loaded colloidal gold nanoparticles were tested in 3D cell cultures to determine their cytotoxicity. Both two and three layer nanoparticles loaded with cisplatin or v paclitaxel showed similar efficacy to drug alone, suggesting their viable use in vivo for cancer treatment.This study has demonstrated the potential use of layered nanoparticles for increasing the delivery of chemotherapeutics deeper into tumor tissue.

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Thiolated chitosan-modified PLA-PCL-TPGS nanoparticles for oral chemotherapy of lung cancer

Cited by 81 publications

References 43 publications

Targeted therapy for human hepatic carcinoma cells using folate-functionalized polymeric micelles loaded with superparamagnetic iron oxide and sorafenib in vitro

Targeted therapy for human hepatic carcinoma cells using folate-functionalized polymeric micelles loaded with superparamagnetic iron oxide and sorafenib in vitro

Preparation, in vitro and in vivo evaluation of polymeric nanoparticles based on hyaluronic acid-poly(butyl cyanoacrylate) and D-alpha-tocopheryl polyethylene glycol 1000 succinate for tumor-targeted delivery of morin hydrate

Study of novel nanoparticle transport and drug release for cancer treatment.

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