Precise glioma targeting of and penetration by aptamer and peptide dual-functioned nanoparticles

Gao, Huile; Qian, Jun; Cao, Sheng‐Li; Liu, Yang; Pang, Zhiqing; Pan, Shuaiqi; Fan, Li; Xi, Zhangjie; Jiang, Xinguo; Zhang, Qizhi

doi:10.1016/j.biomaterials.2012.03.058

Cited by 254 publications

(179 citation statements)

References 40 publications

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“…[24][25][26][27] It has been also reported that intranasal administration of micro/nanoemulsions could have a brain-targeting effect. [28][29][30][31][32][33][34][35][36][37] In the present study, we confirmed that a CLA-PTX microemulsion administered intravenously could also produce antitumor activity in brain tissue.…”

Section: Discussionmentioning

confidence: 99%

Antitumor efficacy of a novel CLA-PTX microemulsion against brain tumors: in vitro and in vivo findings

Li¹,

Yang²,

Li³

et al. 2012

IJN

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Background: Considering the observations that linoleic acid conjugated with paclitaxel (CLA-PTX) possesses antitumor activity against brain tumors, is able to cross the blood-brain barrier, but has poor water solubility, the purpose of this study was to prepare a novel CLA-PTX microemulsion and evaluate its activity against brain tumors in vitro and in vivo. Methods: The in vitro cytotoxicity of a CLA-PTX microemulsion was investigated in C6 glioma cells. The in vivo antitumor activity of the CLA-PTX microemulsion was evaluated in tumorbearing nude mice and rats. The pharmacokinetics of the CLA-PTX microemulsion were investigated in rats, and its safety was also evaluated in mice. Results: The average droplet size of the CLA-PTX microemulsion was approximately 176.3 ± 0.8 nm and the polydispersity index was 0.294 ± 0.024. In vitro cytotoxicity results showed that the IC 50 of the CLA-PTX microemulsion was 1.61 ± 0.83 µM for a C6 glioma cell line, which was similar to that of free paclitaxel and CLA-PTX solution (P . 0.05). The antitumor activity of the CLA-PTX microemulsion against brain tumors was confirmed in our in vivo C6 glioma tumor-bearing nude mice as well as in a rat model. In contrast, Taxol ® had almost no significant antitumor effect in C6 glioma tumor-bearing rats, but could markedly inhibit growth of C6 tumors in C6 glioma tumor-bearing nude mice. The pharmacokinetic results indicated that CLA-PTX in solution has a much longer circulation time and produces higher drug plasma concentrations compared with the CLA-PTX microemulsion. The results of the acute toxicity study showed that the LD 50 of CLA-PTX solution was 103.9 mg/kg. In contrast, the CLA-PTX microemulsion was well tolerated in mice when administered at doses up to 200 mg/kg. Conclusion: CLA-PTX microemulsion is a novel formulation with significant antitumor efficacy in the treatment of brain tumors, and is safer than CLA-PTX solution.

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Section: Discussionmentioning

confidence: 99%

Antitumor efficacy of a novel CLA-PTX microemulsion against brain tumors: in vitro and in vivo findings

Li¹,

Yang²,

Li³

et al. 2012

IJN

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“…Consequently, antibodies to EGFR or EGFRvIII have been conjugated to several nanomedicines for brain tumor targeting. Likewise, antiIL13Rα2 antibodies and IL-13 or IL-4-derived peptides (PEP-1 or AP-1, respectively) have been attached onto the surface of nanomedicines to selectively bind to interleukin receptors [78,79]. To target the folate receptor, folid acid has been used, whereas to target the insulin receptor, the monoclonal antibody 83-14 has been incorporated to nanomedicines, since the use of the physiological ligand in this case was truly restricted by its biological effect on nontarget regions (namely hypoglycemia) [63].…”

Section: Systemic Delivery Of Nanomedicinesmentioning

confidence: 99%

“…Hence, in order to prevent the occurrence of nonspecific side effects, dual-actively targeted have already been designed for achieving optimal targeting after systemic administration. In broad terms, the preclinical studies with these dual-targeted nanomedicines showed more extended survival times over their monotargeted counterparts [65,73,78].…”

Section: Systemic Delivery Of Nanomedicinesmentioning

confidence: 99%

Managing CNS Tumors: The Nanomedicine Approach

Aparicio-Blanco¹,

Torres-Suárez²

2017

New Approaches to the Management of Primary and Secondary CNS Tumors

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Albeit the rapidly evolving knowledge about tumor biochemistry enables various new drug molecules to be designed as treatments, malignant central nervous system (CNS) tumors remain untreatable due to the failure to expose the entire tumor to such therapeutics at pharmacologically meaningful quantities. Therefore, drug delivery in CNS tumors must be properly addressed, as otherwise, novel therapies will continue to fail. In this regard, nanomedicine poses an appealing platform for efficient drug delivery to the CNS, since it may be targeted to improve the drug availability in the site of action, which would be translated into lower drug doses and fewer side effects. Hence, the accumulation of data about the CNS physiology and their relevant receptors, the widening therapeutic armamentarium of drugs potentially useful in CNS chemotherapy and the alternative routes for administration may envisage nanomedicines as a forthcoming routine approach. Indeed, on the basis of the promising results gathered from preclinical studies of nanomedicine-based therapy both systemically and locally administered, some nanomedicines have already been approved for clinical trials in a variety of CNS tumor conditions to serve as the first steps in the translation of nanotherapy to clinic. Their outcome will steer research directions for further improvements.

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“…They conjugated both of them with nanoparticles to establish the glioma cascade delivery system (AsTNP). In vitro cellular uptake and threedimensional tumor spheroid penetration studies have demonstrated that the AsTNP system is not only able to target the endothelial and tumor cells but can also penetrate the endothelial layer and tumor cells to reach the core of the tumor spheroids (41). This is of extreme importance for glioma therapy.…”

Section: Clinical Applications Of Aptamers Imagingmentioning

confidence: 99%

Aptamer for imaging and therapeutic targeting of brain tumor glioblastoma

Delač

Motaln

Ulrich³

et al. 2015

Cytometry Pt A

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Aptamers are short single-stranded nucleic acids (RNA or ssDNA), identified by an in vitro selection process, denominated SELEX, from a partially random oligonucleotide library. They bind to a molecular target, a protein or other complex macromolecular structures of interest with high affinity and specificity, comparable to those of antibodies. Recently, aptamer selection protocols were developed for targeting living cells, including tumors. Chemical modifications of the aptamers and modalities of their detection and delivery systems are already available with high selectivity and targeting ability for the desired cancer cell type, making them promising for diagnosis and therapy. Glioblastoma multiformae represents the most malignant and fatal stage of glioma, and is also the most frequent brain tumor. Glioblastoma-specific aptamers were developed by either targeting the whole cell surface or known glioma biomarkers. These aptamers may gain importance for imaging, tumor cell isolation from biopsies and drug delivery. In biomedical imaging techniques, aptamers coupled with radionuclide or fluorescent labels, bioconjugates and nanoparticles offer an advanced, noninvasive manner for defining the glioblastoma tissue border. Though single modality aptamer imaging probes have some limitations, these are overcome by the use of multimodal probes. Due to selectivity and chemical characteristics, aptamers can be coupled to functionalized nanoparticles and loaded with a drug, appeared promising for in vivo targeting of glioblastoma. Finally, aptamers are effective mediators for gene silencing when coupled to small interfering RNA and a viral vector, thus providing a novel tool with enhanced targeting capability in drug delivery, designed for tailored treatment of glioblastoma patients. V C 2015 International Society for Advancement of Cytometry Key terms aptamer; SELEX; cancer biomarkers; cell and target protein; imaging; drug delivery; glioblastoma; nanoparticles APTAMERS AND THE SELEX TECHNOLOGY IN CANCER APTAMERS, first introduced by Tuerk and Gold (1) and Ellington and Szostak (2), are short chains of DNA or RNA oligonucleotides that bind to small molecules, peptides, and macromolecules, such as proteins of various sizes and conformations. These are identified by an in vitro selection method in a stepwise evolutionary process from a combinatorial library of partial randomized oligonucleotides, consisting of up to 10 15 different sequences and secondary and tertiary structures by a method called SELEX (Systematic Evolution of Ligands by EXponential enrichment). It begins with a pool of variable oligonucleotide sequences with multiple rounds of target exposure of the combinatorial RNA or DNA library, followed by elution of target binders and enrichment of those by RT-PCR or PCR procedures are performed. These results in exponential increase of oligonucleotides with improved ligand to target binding in the previously combinatorial library, which finally is narrowed down to a homogeneous population of high-affinity...

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Precise glioma targeting of and penetration by aptamer and peptide dual-functioned nanoparticles

Cited by 254 publications

References 40 publications

Antitumor efficacy of a novel CLA-PTX microemulsion against brain tumors: in vitro and in vivo findings

Antitumor efficacy of a novel CLA-PTX microemulsion against brain tumors: in vitro and in vivo findings

Managing CNS Tumors: The Nanomedicine Approach

Aptamer for imaging and therapeutic targeting of brain tumor glioblastoma

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