Synthesis and characterization of cisplatin‐loaded, EGFR‐targeted biopolymer and <i>in vitro</i> evaluation for targeted delivery

Xu, Geng; Ye, Haifeng; Feng, Zhen; Lao, Xun; Zhang, Li; Huang, Jing; Wu, Zirong

doi:10.1002/jbm.a.34207

Cited by 13 publications

(13 citation statements)

References 40 publications

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“…CDDP-resistant cancer cells have altered response to the EGF ligand and enhanced the activation of EGFR (23). pEGFR is the activated form of EGFR (24), CDDP induces EGFR activation through the phosphorylation of tyrosine 845, which stabilizes the activation loop of EGFR, maintains the enzyme in the active state, provides a binding surface for protein substrates and leads to cell survival (25).…”

Section: Discussionmentioning

confidence: 99%

Adenovirus-mediated LRIG1 expression enhances the chemosensitivity of bladder cancer cells to cisplatin

et al. 2015

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Abstract. Cisplatin (cis-diaminodichloroplatinum, CDDP) is one of the most effective chemotherapeutic agents that has been widely used in the treatment of many malignancies, including muscle invasive bladder cancer. However, development of CDDP resistance in cancer cells is a major obstacle to the effective treatment of bladder cancer. Therefore, the development of chemosensitizers to overcome the acquired resistance to chemotherapeutic agents is crucial. Previous studies have confirmed that the epidermal growth factor receptor (EGFR) and its signaling pathways are important in the chemoresistance of cancer cells against CDDP-induced cell apoptosis. In a preliminary study we showed that leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is the natural ligand of EGFR, and that the extracellular leucine-rich repeat (LRR) domain and immunoglobulin-like domains of LRIG1 were able to bind to the extracellular domain of EGFR, resulting in the downregulation of EGFR expression. Based on these findings, we hypothesized that LRIG1 may enhance the chemosensitivity of bladder cancer cells to CDDP. In the present study, LRIG1 was overexpressed by the adenovirus vector to determine the effect of LRIG1 on chemosensitivity in the T24 bladder cancer cell line and explored the possible mechanisms. The results showed that CDDP inhibited the growth of the T24 cell line and induced activation of EGFR. Overexpression of LRIG1 increased the inhibitory effect of CDDP on the T24 cell line, which may be associated with inactivation of the EGFR signaling pathway, followed by the decrease of Bcl-2 expression and a concomitantly induced expression of Bax. Based on these results, we concluded that the upregulation of LRIG1 expression inhibited the EGFR signaling pathway, activated the mitochondrial pathway of apoptosis and eventually increased the sensitivity of bladder cancer cells to CDDP. IntroductionBladder cancer is the fourth most common malignant disease worldwide, accounting for ~6% of all cancer cases (1). Bladder cancers (75%) are non-muscle-invasive and can be treated by transurethral resection of the bladder tumor combined with intravesical chemotherapeutic agents instillation. However, the prognosis of patients with muscle invasive bladder cancer (25%) remains poor despite the many advances in treatments made over the past few decades. To improve survival rate and extend life span, patients with muscle invasive bladder cancer require chemotherapy after surgery (2). Cisplatin (CDDP)-based chemotherapy is widely used for treatment of muscle invasive bladder cancer (3). However, cancer cell resistance to CDDP is a major obstacle to the effective treatment of bladder cancer, and the underlying mechanism of the resistance is unclear.The molecular mechanisms of CDDP include binding of the drug to DNA and non-DNA targets to form a variety of monoadducts and cross links, which contribute to the cytotoxicity of CDDP by blocking DNA replication and stimulating signals for apoptosis (4). Despite the excellent anticancer effect...

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Section: Discussionmentioning

confidence: 99%

Adenovirus-mediated LRIG1 expression enhances the chemosensitivity of bladder cancer cells to cisplatin

et al. 2015

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“…There are increasing reports on the use of γ-PGA as a drug carrier. 26,27 Amphiphilic block copolymers composed of γ-PGA-l-phenylalanine ethylester (l-PAE) are very effective in drug delivery applications. 28 In this study, a nano drug carrier system (γ-PGA-l-PAE-TP [PPT]), in which TP was loaded by a γ-PGA-graftedl-PAE copolymer, was fabricated.…”

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confidence: 99%

Fabrication of novel vesicles of triptolide for antirheumatoid activity with reduced toxicity in vitro and in vivo

Zhang

Wang

et al. 2016

IJN

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Triptolide (TP) displays a strong immunosuppression function in immune-mediated diseases, especially in the treatment of rheumatoid arthritis. However, in addition to its medical and health-related functions, TP also exhibits diverse pharmacological side effects, for instance, liver and kidney toxicity and myelosuppression. In order to reduce the side effects, a nano drug carrier system (γ-PGA- l -PAE-TP [PPT]), in which TP was loaded by a poly-γ-glutamic acid-grafted l -phenylalanine ethylester copolymer, was developed. PPT was characterized by photon scattering correlation spectroscopy and transmission electron microscopy, which demonstrated that the average diameter of the drug carrier system is 98±15 nm, the polydispersity index is 0.18, the zeta potential is −35 mV, and the TP encapsulation efficiency is 48.6% with a controlled release manner. The methylthiazolyldiphenyl-tetrazolium bromide assay and flow cytometry revealed that PPT could decrease toxicity and apoptosis induced by free TP on RAW264.7 cells, respectively. The detection of reactive oxygen species showed that PPT could decrease the cellular reactive oxygen species induced by TP. Compared with the free TP-treated group, PPT improved the survival rate of the mice ( P <0.01) and had no side effects or toxic effects on the thymus index ( P >0.05) and spleen index ( P >0.05). The blood biochemical indexes revealed that PPT did not cause much damage to the kidney (blood urea nitrogen and creatinine), liver (serum alanine aminotransferase and aspartate aminotransferase), or blood cells ( P >0.05). Meanwhile, hematoxylin and eosin staining and terminal-deoxynucleotidyl transferase dUTP nick-end labeling staining indicated that PPT reduced the damage of free TP on the liver, kidney, and spleen. Our results demonstrated that PPT reduced free TP toxicity in vitro and in vivo and that it is a promising fundamental drug delivery system for rheumatoid arthritis treatment.

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“…16 The copolymer consisted γ-PGA as the hydrophilic group and l-PAE (H) as hydrophobic side chain. 17,18 To form the copolymer (PH) of PGA and l-PAE, 3.12 g l-PAE was conjugated to 2 g small molecular weight (30 kDa) γ-PGA by amide reaction under the catalyst EDCI for 24 h at room temperature. PH-loaded Rg1 could form the PHR complex.…”

Section: Preparation Of Phromentioning

confidence: 99%

Ginsenoside Rg1 nanoparticle penetrating the blood–brain barrier to improve the cerebral function of diabetic rats complicated with cerebral infarction

Shen¹,

Zhao²,

Wang³

et al. 2017

IJN

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Diabetic cerebral infarction is with poorer prognosis and high rates of mortality. Ginsenoside Rg1 (Rg1) has a wide variety of therapeutic values for central nervous system (CNS) diseases for the neuron protective effects. However, the blood–brain barrier (BBB) restricts Rg1 in reaching the CNS. In this study, we investigated the therapeutic effects of Rg1 nanoparticle (PHRO, fabricated with γ-PGA, L-PAE (H), Rg1, and OX26 antibody), targeting transferrin receptor, on the diabetes rats complicated with diabetic cerebral infarction in vitro and in vivo. Dynamic light scattering analysis shows the average particle size of PHRO was 79±18 nm and the polydispersity index =0.18. The transmission electron microscope images showed that all NPs were spherical in shape with diameters of 89±23 nm. PHRO released Rg1 with sustained release manner and could promote the migration of cerebrovascular endothelial cells and tube formation and even penetrated the BBB in vitro. PHRO could penetrate the BBB with high concentration in brain tissue to reduce the cerebral infarction volume and promote neuronal recovery in vivo. PHRO was promising to be a clinical treatment of diabetes mellitus with cerebral infarction.

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Synthesis and characterization of cisplatin‐loaded, EGFR‐targeted biopolymer and in vitro evaluation for targeted delivery

Cited by 13 publications

References 40 publications

Adenovirus-mediated LRIG1 expression enhances the chemosensitivity of bladder cancer cells to cisplatin

Adenovirus-mediated LRIG1 expression enhances the chemosensitivity of bladder cancer cells to cisplatin

Fabrication of novel vesicles of triptolide for antirheumatoid activity with reduced toxicity in vitro and in vivo

Ginsenoside Rg1 nanoparticle penetrating the blood–brain barrier to improve the cerebral function of diabetic rats complicated with cerebral infarction

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Synthesis and characterization of cisplatin‐loaded, EGFR‐targeted biopolymer and in vitro evaluation for targeted delivery

Cited by 13 publications

References 40 publications

Adenovirus-mediated LRIG1 expression enhances the chemosensitivity of bladder cancer cells to cisplatin

Adenovirus-mediated LRIG1 expression enhances the chemosensitivity of bladder cancer cells to cisplatin

Fabrication of novel vesicles of triptolide for antirheumatoid activity with reduced toxicity in vitro and in vivo

Ginsenoside Rg1 nanoparticle penetrating the blood&ndash;brain barrier to improve the cerebral function of diabetic rats complicated with cerebral infarction

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Ginsenoside Rg1 nanoparticle penetrating the blood–brain barrier to improve the cerebral function of diabetic rats complicated with cerebral infarction