Oxaliplatin-chitosan nanoparticles induced intrinsic apoptotic signaling pathway: A “smart” drug delivery system to breast cancer cell therapy

Vivek, Raju; Thangam, Ramar; NipunBabu, Varukattu; Ponraj, Thondhi; Kannan, Soundarapandian

doi:10.1016/j.ijbiomac.2014.01.054

Cited by 85 publications

(34 citation statements)

References 25 publications

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“…HA nanoparticles-aggregated HET, on the other hand, can induce apoptosis via multiple routes, including mitochondrial-related, caspase-dependent and caspase-independent, as well as ER stress-associated pathways, against bladder carcinoma cells. These findings differed from previous results on mitochondrial and caspase-related apoptotic pathways mediated by biodegraded nanoparticlesencapsulated curcumin and chemotherapeutic 17,23 and further implicated that polymeric nanoparticles may strengthen and diversify apoptotic pathways of compounds. The current results also suggest that HA nanoparticle-aggregation promisingly benefits the anticancer effects of potential and current chemotherapeutics.…”

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confidence: 99%

“…Interestingly, previous works found that biodegraded HA/CHI nanoparticle encapsulation enhances apoptosis and/or antitumor effects originally possessed by curcumin and chemotherapeutic similarly via the mitochondrial-or caspase-associated pathways. 17,23 In the current study, we for the first time revealed that HA nanoparticle-aggregation reinforces the HET-induced apoptosis through the ER stress-associated apoptotic pathways PERK/eIF2α/ATF4/ CHOP and IRE1α/CHOP. Treatment with pure HET with increasing concentration caused more obvious changes in caspases than HA nanoparticles-aggregated HET groups, implicating that for pure HET, caspase-dependent pathways should be more essential routes to induce apoptosis in bladder carcinoma cells.…”

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confidence: 58%

“…21 CHI has also been found to enhance the cytotoxicity and apoptotic induction of chemotherapeutic agent oxaliplatin via mitochondrial-associated pathways. 23 We have previously fabricated the biopolymeric nanoparticles using an electrostatic field system (EFS) in an aqueous-phase environment as the drugs/compounds with antitumor activities have been successfully aggregated by the biopolymeric nanoparticles in the EFS. 16,17 In this study, the natural marine compound HET extracted from a sponge Hippospongia sp.…”

Section: Introductionmentioning

confidence: 99%

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Improvement and enhancement of antibladder carcinoma cell effects of heteronemin by the nanosized hyaluronan aggregation

Huang

Kuo

et al. 2016

IJN

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The effects against tumors exerted by marine active compounds have been highlighted and investigated. Polymeric nanoparticles made from biodegradable and biocompatible molecules such as hyaluronan (HA) and chitosan (CHI) are able to aggregate the compounds to enhance their activities against tumor cells and reduce the toxicity on normal cells. Here, we extensively examined the antitumor activities and the mechanisms of HA/CHI nanoparticles-aggregated heteronemin (HET) extracted from the sponge Hippospongia sp. The half-maximal inhibitory concentration (IC 50 ) of pure HET toward T24 bladder carcinoma cells is ~0.28 µg/mL. Pure HET from 0.2 to 0.8 µg/mL and HA nanoparticles-aggregated HET at 0.1 and 0.2 µg/mL significantly reduced T24 cell viability. Compared to pure HET, HA nanoparticles/HET aggregates showed much weaker viability-inhibitory effects on L929 normal fibroblasts. HET dose-dependently suppressed cancer cell migration as HA/CHI nanoparticles-aggregated HET displayed stronger migration-inhibitory effects than pure HET. Flow cytometric analysis showed that pure HET increased early/total apoptosis and JC-1 monomer fluorescence, while HA/CHI nanoparticles-aggregated HET induced higher apoptosis and JC-1 monomer rates than pure HET, suggesting that aggregation of HA nanoparticles offers HET stronger apoptosis-inducing capacity through mitochondrial depolarization. Western blot analysis showed that HA nanoparticles-aggregated HET further increased mitochondrial-associated, caspase-dependent and caspase-independent, as well as endoplasmic reticulum stress-related factors in comparison with pure HET. These data indicated that pure HET possesses cytotoxic, antimigratory, and apoptosis-inducing effects on bladder cancer cells in vitro, and its induction of apoptosis in bladder carcinoma cells is mainly caspase dependent. Moreover, HA nanoparticle aggregation reinforced the cytotoxic, antimigratory, and apoptosis-inducing activities against bladder carcinoma cells and attenuated the viability-inhibitory effects on normal fibroblasts. This aggregation reinforces antibladder carcinoma effects of HET via diverse routes, including mitochondrial-related/caspase-dependent, caspase-independent, and endoplasmic reticulum stress-related pathways. The current data also strongly suggested that HA/CHI nanoparticles-aggregated HET would be a potential treatment for urothelial cancer in vivo.

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confidence: 58%

Section: Introductionmentioning

confidence: 99%

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Improvement and enhancement of antibladder carcinoma cell effects of heteronemin by the nanosized hyaluronan aggregation

Huang

Kuo

et al. 2016

IJN

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“…For example, they are not antigenic, can be metabolized, have high stability and allow for high loading for water soluble active substances (Muller et al, 1996). Chitosan, a natural biodegradable polymer, is often used in the preparation of particular dosage forms (Bodmeier, Oh, Pramar, 1989;Aral, Akbuğa, 1998;Shu, Zhu, 2002;Norkar, Sher, Pawar, 2010;Sharma et al, 2012;Al-Qadi et al, 2012, Zhang, Wang, Pan, 2014Vivek et al, 2014;Koppolu et al, 2014;Xue et al, 2015;Chen et al, 2016;Ganguly, Kulkarni, Aminabhavi, 2016). A cationic linear bioamino polysaccharide, chitosan, is obtained by means of alkali distillation of chitin (Illum, 1998).…”

Section: Introductionmentioning

confidence: 99%

Investigation of the parameters affecting the release of flurbiprofen from chitosan microspheres

Tilkan

Özdemir

2018

Braz. J. Pharm. Sci.

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Flurbiprofen (FLB), a NSAID, widely used for preventing pain generally for arthritis or dental problems. In this study, FLB loaded chitosan microspheres were prepared by ionotropic gelation method. In this method, microspheres were formed by dropping chitosan solutions containing FLB into sodium alginate solutions including sodium tripolyphosphate (TPP). A variety of formulation parameters like drug:polymer ratio, drug concentration, polymer's molecular weight, polymer concentration, pH and the concentration of TPP solutions, drying method and stirring time were analyzed. The dissolution studies were performed in a shaking water bath in pH 7.4 phosphate buffer saline (PBS) at 37 °C. Laser diffractometer was used for particle size analysis, and scanning electron microscope (SEM) was used for morphological properties. Drug loading and loading efficiency were calculated by using UV spectrophotometer. The particles obtained were spherical with 0.7-1.3 mm size range, and the loading efficiency was approximately 21-79%. The dissolution studies conducted revealed that drug:polimer ratio and the polymer type and concentration affected the drug release from microspheres. It was observed that increasing the polymer concentration, polymer's molecular weight and TPP concentration decreased the FLB release from microspheres, which was according to Higuchi kinetics.

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“…The achievement of a local, controlled delivery of the drug at the target site would allow keeping the systemic concentration of the drug low. In this regard, other Authors reported that "ideal smart nanoparticles" for redox and pH-responsive drug delivery system (DDS) should enhance therapeutic efficacy thus reducing side effects due to bioaccumulation [6,7].…”

Section: Introductionmentioning

confidence: 99%

Redox-active Microcapsules as Drug Delivery System in Breast Cancer Cells and Spheroids

Colone¹,

Kaliappan²,

Calcabrini³

et al. 2016

J Mol Genet Med

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The purpose of our study was to develop new delivery systems for drugs effective against breast cancer by using biodegradable and biocompatible capsules. Redox-active microcapsules based on thiolated polymethacrylic acid (PMA) were employed. The interaction of these PMA SH capsules with breast cancer cells and the mechanism of their internalization was investigated. PMA SH biocompatibility was evaluated by MTT assay. To analyze their potential as drug carrier, we incorporated doxorubicin into the capsules. Confocal microscopy observations showed the presence of capsules inside the cells. Although some drug molecules still appeared co-localized with PMA SH capsules, strong doxorubicin fluorescence was observed both in the cytoplasm and nucleus, indicating the disassembling of the capsule into PMA SH -drug conjugate after internalization. These results were confirmed by both flow cytometry (time course of capsule uptake) and scanning electron microscopy. PMA SH capsules were also internalized in 3D cell structures (spheroids) suggesting their potential use as drug delivery system for treatment of human diseases.

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Oxaliplatin-chitosan nanoparticles induced intrinsic apoptotic signaling pathway: A “smart” drug delivery system to breast cancer cell therapy

Cited by 85 publications

References 25 publications

Improvement and enhancement of antibladder carcinoma cell effects of heteronemin by the nanosized hyaluronan aggregation

Improvement and enhancement of antibladder carcinoma cell effects of heteronemin by the nanosized hyaluronan aggregation

Investigation of the parameters affecting the release of flurbiprofen from chitosan microspheres

Redox-active Microcapsules as Drug Delivery System in Breast Cancer Cells and Spheroids

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