Development of dual ligand-targeted polymeric micelles as drug carriers for cancer therapy in vitro and in vivo

Yu, Junhua; Xie, Xin; Xu, Xiaoyuan; Zhang, Lei; Zhou, Xueyun; Yu, Hui; Wu, Ping; Wang, Ting; Che, Xiangxin; Hú, Zhìhóng

doi:10.1039/c3tb21539c

Cited by 36 publications

(29 citation statements)

References 51 publications

(52 reference statements)

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“…Based on the in vitro subcellular fractionation using cells expressing high levels of HER2 (MDA-MB-231, MDA-MB-361 and SK-BR-3 cells lines), the NLS block copolymer micelles showed higher accumulation in the nuclei and the duel targeting platform exhibited an improved antiproliferative effect. Yu et al [211] also employed the dual targeted strategy and fabricated DOX loaded folic acid and NLS (Ac-CGYGPKKKRKVGG) functionalized chitosan (modified with cholesterol) micelles (~250 nm). The dual targeting led to a higher cellular uptake (KB cells) because of the folic acid and increased nucleus localization due to the NLS, and highest tumor suppression (KB tumor xenograft models, BALB/c nude mice) when compared to the nontargeted or singly targeted DOX loaded micelles.…”

Section: Intracellular Trafficking and Subcellular Targetingmentioning

confidence: 99%

Insight into nanoparticle cellular uptake and intracellular targeting

Yameen

Choi

Vilos

et al. 2014

Journal of Controlled Release

632

476

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Collaborative efforts from the fields of biology, materials science, and engineering are leading to exciting progress in the development of nanomedicines. Since the targets of many therapeutic agents are localized in subcellular compartments, modulation of nanoparticle-cell interactions for an efficient cellular uptake through the plasma membrane, and the development of nanomedicines for precise delivery to subcellular compartments remain formidable challenges. The cellular internalization routes have a determining effect on the post-internalization fate and intracellular localization of nanoparticles. This review highlights the cellular uptake routes most relevant to the field of non-targeted nanomedicine, and presents an account of ligand targeted nanoparticles for receptor mediated cellular internalization as a strategy for modulating the cellular uptake of nanoparticles. Ligand targeted nanoparticles have been the main impetus behind the progress of nanomedicines towards the clinic. This strategy has even resulted in a remarkable development towards effective oral delivery of nanomedicines that can overcome the intestinal epithelial cellular barrier. A detailed overview of the recent developments towards subcellular targeting that is emerging as a platform for the next generation organelle specific nanomedicines is also provided. Each section of the review includes prospect, potential, and concrete expectations from the field of targeted nanomedicines and strategies to meet those expectations.

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Section: Intracellular Trafficking and Subcellular Targetingmentioning

confidence: 99%

Insight into nanoparticle cellular uptake and intracellular targeting

Yameen

Choi

Vilos

et al. 2014

Journal of Controlled Release

632

476

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“…And the chemical structure of CHGC was confirmed by 1 H NMR spectra (Figure 2). Compared with glycol chitosan, the new signal at 1.27 ppm belonged to methene hydrogen of cholesterol hemisuccinate group, indicating that CHGC conjugate was successfully synthesized [31,32]. According to the colloidal titration test, the degree of substitution was 5.8 cholesterol groups per 100 sugar residues of glycol chitosan.…”

Section: Synthesis and Characterization Of Pcp-chgcmentioning

confidence: 96%

“…Notably, it was unlikely that such a high concentration of DOX⋅HCl would be present in the tumor site during the blood circulation in vivo. And DOX-loaded micelles may facilitate its accumulation at tumor tissue by the EPR effect as previously described [31,43]. For comparison, the cytotoxicity of the empty micelles was also investigated.…”

Section: In Vitro Cellular Uptake Studymentioning

confidence: 97%

“…= 28 kDa) was obtained by enzymatic degradation of 75.2% deacetylated glycol chitosan [31,32], which was purchased from Wako Pure Chemical Industries, Ltd. (Osaka, Japan). Cholesterol, succinic anhydride, 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDC), and 4-(N-maleimidomethyl)cyclohexanecarboxylic acid N-hydroxysuccinimide ester (SMCC) were all provided by Sigma-Aldrich (St. Louis, MO, USA).…”

Section: Materials Glycol Chitosan (mentioning

confidence: 99%

“…. CHGC conjugate was synthesized by using our previous method with little modification [31]. Briefly, cholesterol and succinic anhydride were mixed and reacted for 24 h. Then cholesterol hemisuccinate was obtained by purification and recrystallization.…”

Section: Synthesis Of Chgc Conjugatementioning

confidence: 99%

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Development, Characterization, and Evaluation of PSMA-Targeted Glycol Chitosan Micelles for Prostate Cancer Therapy

et al. 2014

Journal of Nanomaterials

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Prostate cancer-binding peptides- (PCP-) modified polymeric micelles were prepared and used for the treatment of prostate-specific membrane antigen- (PSMA-) expressing prostate cancer in a target-specific manner. Cholesterol-modified glycol chitosan (CHGC) was synthesized. PCP-conjugated CHGC (PCP-CHGC) micelles were fabricated and characterized. The degree of substitution was 5.2 PCP groups and 5.8 cholesterol groups per 100 sugar residues of glycol chitosan. The critical aggregation concentration (CAC) of PCP-CHGC copolymer was 0.0254 mg/mL. Doxorubicin (DOX) was chosen as a model antitumor drug. The DOX-loaded micelles were prepared by an o/w method. The mean diameter of DOX-loaded PCP-CHGC (DOX-PCP-CHGC) micelles was 293 nm determined by dynamic light scattering (DLS). DOX released from drug-loaded micelles was in a biphasic manner. DOX-PCP-CHGC micelles exhibited higher cytotoxicityin vitroagainst PSMA-expressing LNCaP cells than DOX-loaded CHGC (DOX-CHGC) micelles. Moreover, the cellular uptake of DOX-PCP-CHGC micelles determined by confocal laser scanning microscopy (CLSM) and flow cytometry was higher than that of DOX-CHGC micelles in LNCaP cells. Importantly, DOX-PCP-CHGC micelles demonstrated stronger antitumor efficacy against LNCaP tumor xenograft models than doxorubicin hydrochloride and DOX-CHGC micelles. Taken together, this study provides a potential way in developing PSMA-targeted drug delivery system for prostate cancer therapy.

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