Functional alginate nanoparticles for efficient intracellular release of doxorubicin and hepatoma carcinoma cell targeting therapy

Guo, Hua; Lai, Quanyong; Wang, Wei; Wu, Yukun; Zhang, Chuangnian; Liu, Yuan; Yuan, Zhi

doi:10.1016/j.ijpharm.2013.04.025

Cited by 98 publications

(40 citation statements)

References 43 publications

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“…DOX was covalently conjugated via pH-sensitive hydrazone bond and was released from the NCs at low pH value in endosomal-lysosomal pathway (pH 4-6) in cancerous cells (She et al 2013). A broad distribution of DOX fluorescence in the cells after 3 h indicated that small amount of DOX was released from NCs and still remains conjugated to the polymer which is in conformity with the findings reported literature (Guo et al 2013;Shuai et al 2004). The pHbased time-dependent phenomenon of DOX release from NCs could be reason for delayed nuclear uptake in HEK293 cells.…”

Section: In Vitro Transfection Studysupporting

confidence: 89%

Self-assembled nanocomplexes of anionic pullulan and polyallylamine for DNA and pH-sensitive intracellular drug delivery

et al. 2014

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The amalgamation of chemotherapy and gene therapy is promising treatment option for cancer. In this study, novel biocompatible self-assembled nanocomplexes (NCs) between carboxylmethylated pullulan t335 (CMP) with polyallylamine (CMP-PAA NCs) were developed for plasmid DNA (pDNA) and pH-sensitive doxorubicin (DOX) delivery. DOX was conjugated to CMP (DOX-CMP) via hydrazone and confirmed by FTIR and 1 H-NMR. In vitro release studies of pH-sensitive DOX-CMP conjugate showed 23 and 85 % release after 48 h at pH 7.4 (physiological pH) and pH 5 (intracellular/tumoral pH), respectively. The CMP-PAA NCs or DOX-CMP-PAA NCs self-assembled into a nanosized (\250 nm) spherical shape as confirmed by DLS and TEM. The hemolysis and cytotoxicity study indicated that the CMP-PAA NCs did not show cytotoxicity in comparison with plain polyallylamine. Gel retardation assay showed complete binding of pDNA with CMP-PAA NCs at 1:2 weight ratio. CMP-PAA NCs/pDNA showed significantly higher transfection in HEK293 cells compared to PAA/pDNA complexes. Confocal imaging demonstrated successful cellular uptake of DOX-CMP-PAA NCs in HEK293 cells. Thus, NCs hold great potential for targeted pDNA and pH-sensitive intratumoral drug delivery.

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Section: In Vitro Transfection Studysupporting

confidence: 89%

Self-assembled nanocomplexes of anionic pullulan and polyallylamine for DNA and pH-sensitive intracellular drug delivery

et al. 2014

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“…As described above, only 45% of Dox were released from the drug carrier in 48 h. The released Dox contributed to the cytotoxicity of Dox-loaded micelles. The actual cytotoxicity of Dox-loaded micelles should be greater along with the extension of time [31]. Notably, TOS can target mitochondria, leading to promote the mitochondria-specific apoptotic pathways [20].…”

Section: Resultsmentioning

confidence: 99%

Preparation, Characterization and Evaluation of α-Tocopherol Succinate-Modified Dextran Micelles as Potential Drug Carriers

Zhou

Chen

et al. 2015

Materials

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In the present study, α-tocopherol succinate (TOS) conjugated dextran (Dex-TOS) was synthesized and characterized by fourier transform infrared (FT-IR) spectroscopy, 1H nuclear magnetic resonance (1H NMR), dynamic light scattering (DLS) and fluorescence spectroscopy. Dex-TOS could form nanoscaled micelles in aqueous medium. The critical micelle concentration (CMC) is 0.0034 mg/mL. Doxorubicin (Dox) was selected as a model drug. Dox-loaded Dex-TOS (Dex-TOS/Dox) micelles were prepared by a dialysis method. The size of Dex-TOS/Dox micelles increased from 295 to 325 nm with the Dox-loading content increasing from 4.21% to 8.12%. The Dex-TOS/Dox micelles were almost spherical in shape, as determined by transmission electron microscopy (TEM). In vitro release demonstrated that Dox release from the micelles was in a sustained manner for up to 96 h. The cellular uptake of Dex-TOS/Dox micelles in human nasopharyngeal epidermoid carcinoma (KB) cells is an endocytic process determined by confocal laser scanning microscopy (CLSM). Moreover, Dex-TOS/Dox micelles exhibited comparable cytotoxicity in contrast with doxorubicin hydrochloride. These results suggested that Dex-TOS micelles could be a promising carrier for drug delivery.

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“…Polymeric nanoparticles (NPs) to be developed as anticancer drug transporters are recently emerging because of the promise in both their protection of the drug from rapid metabolism or clearance and their selective accumulation in tumorous tissues via the enhanced permeability and retention (EPR) effect caused by the vascular architecture difference of tumorous tissue and the poor lymphatic drainage system [1]. Among a variety of polymeric NPs for targeting delivery of anticancer drugs, the NPs based on natural polysaccharides, such as heparin [2], dextran [3], curdlan [4], xyloglucan [5], arabinogalactan [6], hyaluronic acid [7,8], alginate [9][10][11][12], pullulan [13][14][15][16][17], and chitosan [18][19][20][21][22][23][24][25], have attracted the attention of pharmacologists. In particular, pullulan has aroused scientists' increasing interest due to its specific structure and outstanding biological properties, such as biocompatibility, biodegradability, low immunogenicity, nontoxicity, and water solubility.…”

Section: Introductionmentioning

confidence: 99%

Facile One-Pot Synthesis of Self-Assembled Folate-Biotin-Pullulan Nanoparticles for Targeted Intracellular Anticancer Drug Delivery

Wang

Huang

Wang

et al. 2016

Journal of Nanomaterials

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The self-assembled folate-biotin-pullulan (FBP) nanoparticles (NPs) were prepared by facile one-pot synthesis and their physicochemical properties were characterized. The self-assembled FBP NPs were used as an anticancer drug nanocarrier entrapping doxorubicin (DOX) for targeting folate-receptors-overexpressing cancer cells. The identification of prepared NPs to folate-receptor-expressing cancer cells (KB cells) was affirmed by cell viability measurement, folate competition test, and flow cytometric analysis. Compared with the naked DOX and DOX/BP NPs, the DOX/FBP NPs had lower IC50value compared to KB cells as a result of the folate-receptor-mediated endocytosis process. The cytotoxicity of DOX/FBP NPs to KB cells could be inhibited competitively by free folate. The cellular intake pattern of naked DOX and drug-loaded NPs was identified by confocal laser scanning microscopy (CLSM) observation and the higher cellular uptake of drug for DOX/FBP NPs over naked DOX was observed. The prepared FBP NPs had the potential to be used as a powerful carrier to target anticancer drugs to folate-receptor-expressing tumor cells and reduce cytotoxicity to normal tissues.

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Functional alginate nanoparticles for efficient intracellular release of doxorubicin and hepatoma carcinoma cell targeting therapy

Cited by 98 publications

References 43 publications

Self-assembled nanocomplexes of anionic pullulan and polyallylamine for DNA and pH-sensitive intracellular drug delivery

Self-assembled nanocomplexes of anionic pullulan and polyallylamine for DNA and pH-sensitive intracellular drug delivery

Preparation, Characterization and Evaluation of α-Tocopherol Succinate-Modified Dextran Micelles as Potential Drug Carriers

Facile One-Pot Synthesis of Self-Assembled Folate-Biotin-Pullulan Nanoparticles for Targeted Intracellular Anticancer Drug Delivery

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