Rational Design of Polymeric Hybrid Micelles with Highly Tunable Properties to Co‐Deliver MicroRNA‐34a and Vismodegib for Melanoma Therapy

Li, Hanmei; Fu, Yao; Zhang, Ting; Li, Yanping; Hong, Xiaoyu; Jiang, Jiayu; Gong, Tao; Zhang, Zhirong; Sun, Xun

doi:10.1002/adfm.201503115

Cited by 42 publications

(28 citation statements)

References 44 publications

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“…Colocalization of mixed micelles with endosome/lysosome (visible as yellow fluorescence) was observed 5 min and 2 h after micelles were added to cells. The overlaps with the lysotracker staining revealed that the mixed micelles were efficiently taken up into the endosome/lysosomal compartments, indicating a lysosomal pathway after internalization . And both PPN MM and PPF MM showed extensive distribution in the cytoplasm.…”

Section: Resultsmentioning

confidence: 90%

“…Polycaprolactone (PCL) is a biodegradable polymer that has been approved by the US Food and Drug Administration for applications in the human body such as sutures, tissue scaffolds, and adhesion barriers . PCL‐derived diblock copolymers have been extensively used in controlled release and targeted drug delivery . Herein, we report the synthesis of a d ‐fructose conjugated diblock copolymer poly(ε‐caprolactone)‐poly(ethylene glycol) (PCL‐PEG‐Fru) via click chemistry.…”

Section: Introductionmentioning

confidence: 99%

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d‐Fructose Modification Enhanced Internalization of Mixed Micelles in Breast Cancer Cells via GLUT5 Transporters

Qin

Gong

et al. 2017

Macromolecular Bioscience

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d-Fructose modified poly(ε-caprolactone)-polyethylene glycol (PCL-PEG-Fru) diblock amphiphile is synthesized via Cu(I)-catalyzed click chemistry, which self-assembles with D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) into PCL-PEG-Fru/TPGS mixed micelles (PPF MM). It has been proven that glucose transporter (GLUT)5 is overexpressed in MCF-7 cells other than L929 cells. In this study, PPF MM exhibit a significantly higher uptake efficiency than fructose-free PCL-PEG-N /TPGS mixed micelles in both 2D MCF-7 cells and 3D tumor spheroids. Also, the presence of free d-fructose competitively inhibits the internalization of PPF MM in MCF-7 cells other than L929 cells. PPF MM show selective tumor accumulation in MCF-7 breast tumor bearing mice xenografts. Taken together, PPF MM represent a promising nanoscale carrier system to achieve GLUT5-mediated cell specific delivery in cancer therapy.

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Section: Resultsmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

d‐Fructose Modification Enhanced Internalization of Mixed Micelles in Breast Cancer Cells via GLUT5 Transporters

Qin

Gong

et al. 2017

Macromolecular Bioscience

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“…Among the available delivery systems, biodegradable polymeric nanoparticles have been the most successful delivery platforms used in drug/nucleic acid combinations [8–10]. Polymeric nanoparticles are typically composed of pharmacologically inert polymer suitable for encapsulation of both types of therapeutic cargos [11]. However, the manufacturing complexity and unsatisfactory drug loading ability of the traditional nanoparticles remain a significant hurdle for their clinical translation.…”

Section: Introductionmentioning

confidence: 99%

Self-immolative nanoparticles for simultaneous delivery of microRNA and targeting of polyamine metabolism in combination cancer therapy

Xie

Murray-Stewart

Wang

et al. 2017

Journal of Controlled Release

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Combination of anticancer drugs with therapeutic miRNA has emerged as a promising anticancer strategy. However, the promise is hampered by a lack of desirable delivery systems. We report on the development of self-immolative nanoparticles capable of simultaneously delivering miR-34a mimic and targeting dysregulated polyamine metabolism in cancer. The nanoparticles were prepared from a biodegradable polycationic prodrug, named DSS-BEN, which was synthesized from a polyamine analog N1,N11-bisethylnorspermine (BENSpm). The nanoparticles were selectively disassembled in the cytoplasm where they released miRNA. Glutathione (GSH)-induced degradation of self-immolative linkers released BENSpm from the DSS-BEN polymers. MiR-34a mimic was effectively delivered to cancer cells as evidenced by upregulation of intracellular miR-34a and downregulation of Bcl-2 as one of the downstream targets of miR-34a. Intracellular BENSpm generated from the degraded nanoparticles induced the expression of rate-limiting enzymes in polyamine catabolism (SMOX, SSAT) and depleted cellular natural polyamines. Simultaneous regulation of polyamine metabolism and miR-34a expression by DSS-BEN/miR-34a not only enhanced cancer cell killing in cultured human colon cancer cells, but also improved antitumor activity in vivo. The reported findings validate the self-immolative nanoparticles as delivery vectors of therapeutic miRNA capable of simultaneously targeting dysregulated polyamine metabolism in cancer, thereby providing an elegant and efficient approach to combination nanomedicines.

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“…Polymer hybrid micelles (PHMs), consisting of different amphiphilic diblock copolymers, have become promising carriers for co-delivery of nucleic acids and small-molecule drugs 10 . In general, nanoparticle-based drug delivery systems can efficiently co-deliver hydrophobic drugs and nucleic acids to tumors 11 - 13 .…”

Section: Introductionmentioning

confidence: 99%

Rational design of Polymeric Hybrid Micelles to Overcome Lymphatic and Intracellular Delivery Barriers in Cancer Immunotherapy

Wang

et al. 2017

Theranostics

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Poor distribution of antigen/adjuvant to target sites and inadequate induction of T cell responses remain major challenges in cancer immunotherapy because of the lack of appropriate delivery systems. Nanocarrier-based antigen delivery systems have emerged as an innovative strategy to improve vaccine efficacy. Here we present polymeric hybrid micelles (PHMs) as a simple and potent antigen/adjuvant co-delivery system with highly tunable properties. PHMs consist of two amphiphilic diblock copolymers, polycaprolactone-polyethylenimine (PCL-PEI) and polycaprolactone-polyethyleneglycol (PCL-PEG). PHMs with different proportions of cationic PCL-PEI were prepared and loaded with tyrosinase-related protein 2 (Trp2) peptide and adjuvant CpG oligodeoxynucleotide to generate the Trp2/PHM/CpG co-delivery system. Lymphatic and intracellular antigen delivery as a function of PCL-PEI proportion was evaluated in vitro and in vivo. PHMs containing 10% (w/w) PCL-PEI (Trp2/PHM10/CpG) showed the optimal balance of good distribution to lymph nodes, strong immunization effect after subcutaneous administration, and low toxicity to dendritic cells. In a mouse model of B16F10 melanoma, Trp2/PHM10/CpG showed significantly higher antigen-specific cytotoxic T lymphocyte activity and greater anticancer efficacy than Trp2/PHM0/CpG without PCL-PEI or a mixture of free Trp2 and CpG. These results provide new insights into how cationic segments affect the efficiency of antigen delivery by cationic nanocarriers. They also suggest that PHMs can serve as a structurally simple and highly tunable platform for co-delivery of antigen and adjuvant in cancer immunotherapy.

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Rational Design of Polymeric Hybrid Micelles with Highly Tunable Properties to Co‐Deliver MicroRNA‐34a and Vismodegib for Melanoma Therapy

Cited by 42 publications

References 44 publications

d‐Fructose Modification Enhanced Internalization of Mixed Micelles in Breast Cancer Cells via GLUT5 Transporters

d‐Fructose Modification Enhanced Internalization of Mixed Micelles in Breast Cancer Cells via GLUT5 Transporters

Self-immolative nanoparticles for simultaneous delivery of microRNA and targeting of polyamine metabolism in combination cancer therapy

Rational design of Polymeric Hybrid Micelles to Overcome Lymphatic and Intracellular Delivery Barriers in Cancer Immunotherapy

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