Gene therapy for nucleus pulposus regeneration by heme oxygenase-1 plasmid DNA carried by mixed polyplex micelles with thermo-responsive heterogeneous coronas

Feng, Ganjun; Chen, Hongying; Li, Junjie; Huang, Qiang; Gupte, Melanie J.; Líu, Hao; Song, Yueming; Ge, Zhishen

doi:10.1016/j.biomaterials.2015.02.024

Cited by 46 publications

(30 citation statements)

References 45 publications

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“…This toxicity is the result of cationic PHMs nonspecifically interacting with blood plasma proteins and erythrocytes, causing the formation of aggregates that can occlude the pulmonary vasculature. [1c], At the other extreme, animals injected with PHM‐2 showed pulmonary histology similar to that of the control group (Figure S7, Supporting Information). Induction of immune response as measured by serum levels of the proinflammatory cytokine IL‐12 decreased with increasing amount of PCL‐PEG (Figure S8, Supporting Information).…”

Section: Resultsmentioning

confidence: 82%

“…In 2013, a miR‐34 mimic has become the first miRNA to reach phase I clinical trials, indicated that miR‐34a‐based therapy has great potential in cancer treatment. [1b] Overexpression of miR‐34a in melanoma cells induces cell apoptosis and inhibits cell migration and tumor growth in vivo . VIS was a Hh pathway inhibitor approved in 2012 for the treatment of basal cell carcinoma.…”

Section: Resultsmentioning

confidence: 99%

“…In recent years, nucleic acid therapeutics such as microRNAs (miRNAs), small interfering RNA, and plasmid DNA have shown great promise in cancer treatment . Cancers are complex diseases involving multiple signaling pathways, and their progression is marked by many successive mutations in a line of cells .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Zhang

et al. 2015

Adv Funct Materials

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wileyonlinelibrary.comA polymeric hybrid micelle (PHM) system with highly tunable properties is reported to co-deliver small molecule and nucleic acid drugs for cancer therapy; this system is structurally simple and easy-to-fabricate. The PHM consists of two amphiphilic diblock copolymers, polycaprolactone-polyethylenimine (PCL-PEI) and polycaprolactone-polyethyleneglycol (PCL-PEG). PHMs are rationally designed with different physicochemical properties by simply adjusting the ratio of the two diblock copolymers and the near neutral PHM-2 containing a low ratio of PCL-PEI achieves the optimal balance between high tumor distribution and subsequent cellular uptake after intravenous injection. Encapsulating Hedgehog (Hh) pathway inhibitor vismodegib (VIS) and microRNA-34a (miR-34a) into PHM-2 generates the VIS/ PHM-2/34a co-delivery system. VIS/PHM-2/34a shows synergistic anticancer effi cacy in murine B16F10-CD44 + cells, a highly metastatic tumor model of melanoma. VIS/PHM-2/34a synergistically attenuates the expression of CD44, a vital receptor indicating the metastasis of melanoma. Intriguingly, inhibiting Hh pathway by VIS is accompanied by downregulation of CD44 expression, revealing that Hh signaling might be an upstream regulator of CD44 expression in melanoma. Thus, co-delivery of miR-34a and VIS demonstrates great potential in cancer therapy, and PHM offers a structurally simple and highly tunable platform for the co-delivery of small molecule and nucleic acid drugs in tumor combination therapy.

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Section: Resultsmentioning

confidence: 82%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

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

Zhang

et al. 2015

Adv Funct Materials

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“…One important approach of gene therapy for IDD is to correct the imbalance between anabolism and catabolism within the disc ECM. It has been reported that administration of heme oxygenase-1 (HO-1) plasmid DNA carried by mixed polyplex micelles with thermo-responsive heterogeneous coronas can diminish MMP-3 activity and increase Col II and aggrecan contents in rat NP cells, indicating a potential protective effect of HO-1 on IDD [115]. Introduction of IL-1 receptor antagonist into human degenerate IVD explants using genetically engineered constructs leads to elimination of matrix degradation due to decreased expression of MMP-3, MMP-7 and MMP-13 [116].…”

Section: Therapeutic Potential Of Targeting Mmps and Adamtss In Iddmentioning

confidence: 99%

MMPs and ADAMTSs in intervertebral disc degeneration

Wang

et al. 2015

Clinica Chimica Acta

164

124

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“…Polyplex micelles are expected as alternatives to viral vectors due to the finely tuned properties for specific applications by altering the structure of the polycation used for polyplex formation. [8][9][10][11] Kataoka et al synthesized poly(aspartamide) derivatives with an ethylenediamine unit as a side chain (poly{N-[N-(2-aminoethyl)-2-aminoethyl] aspartamide} (PAsp(DET)) and their block copolymers with poly(ethylene glycol) (PEGPAsp(DET)) as novel biodegradable polycations for higher gene transfection efficiency. 12,13) Polyplex micelles formed with pDNA, PAsp(DET), and PEG-PAsp(DET) exhibited effective endosomal escape properties based on the di-protonation of diamine side chains with decreasing pH, which improved their transfection efficiency with minimal toxicity, and they are promising candidates for local gene transfer.…”

mentioning

confidence: 99%

Development of New Formulation Dry Powder for Pulmonary Delivery Using Amino Acids to Improve Stability

Suzuki

Okuda

Okamoto

2016

Biological & Pharmaceutical Bulletin

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Cationic polymers are being studied as non-viral gene delivery vectors. Poly{N-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} (PAsp(DET)) and their block copolymers with poly(ethylene glycol), PEG-PAsp(DET), have been reported as efficient biodegradable non-viral vectors which form a polyplex with plasmid DNA (pDNA). However, the polyplexes are not stable because PAsp(DET) and PEG-PAsp(DET) are easily subjected to hydrolysis; therefore, they need to be prepared on site. In this study, using the biodegradable polycations as non-viral vectors, PAsp(DET) and PEG-PAsp(DET), we investigated the effects of L-leucine (Leu) on the polyplex. We prepared solutions and dry powders with and without Leu. Both dry powders had large and porous particles and Leu acted as a dispersing agent. The transfection activity of the sample solutions decreased within a month. However, the decrease in the transfection activity was partially suppressed by the dry powder with Leu at 5 and 25°C at 3 months. Furthermore, transfection experiments revealed that Leu exhibited a pDNA-stabilizing effect in the solution and dry powder. Similar results were observed for pDNA integrity, where a polyplex was formed in the dry powder. The results suggest that Leu is a candidate stabilizer to protect pDNA from degradation.

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Gene therapy for nucleus pulposus regeneration by heme oxygenase-1 plasmid DNA carried by mixed polyplex micelles with thermo-responsive heterogeneous coronas

Cited by 46 publications

References 45 publications

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

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

MMPs and ADAMTSs in intervertebral disc degeneration

Development of New Formulation Dry Powder for Pulmonary Delivery Using Amino Acids to Improve Stability

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