Esterase‐Activated Charge‐Reversal Polymer for Fibroblast‐Exempt Cancer Gene Therapy

Qiu, Nasha; Liu, Xiangrui; Zhong, Yin; Zhou, Zhuxian; Piao, Ying; Miao, Lei; Zhang, Qianzhi; Tang, Jianbin; Huang, Leaf; Shen, Youqing

doi:10.1002/adma.201603095

Cited by 206 publications

(171 citation statements)

References 52 publications

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“…About 35% APO was detected after 24 h incubation with esterase (220 U mL −1 ), much higher than the PBS group (Figure 1d,e). On the other hand, the esterase activity of microglia cell was detected using fluorescein diacetate (FDA) . The result showed a relatively enhanced esterase activity in BV2 cells (a murine microglia cell line) after inflammatory stimulation (about 3.4 folds, p < 0.01) (Figure 1f,g).…”

Section: Resultsmentioning

confidence: 99%

Scar Tissue‐Targeting Polymer Micelle for Spinal Cord Injury Treatment

Wang

Liang

et al. 2020

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Spinal cord injury (SCI) is a devastating disorder, leading to permanent motor and sensory deficit. Despite recent advances in neurosciences, the treatment efficacy on SCI patients remains unsatisfactory, mainly due to the poor accumulation, short retention, and lack of controlled release of therapeutics in lesion tissue. Herein, an injured spinal cord targeting prodrug polymer micelle is built. An esterase‐responsive bond is used to link apocynin (APO) monomer, because of the enhanced esterase activity found in microglia cells after activation, which ensures a controlled degradation of APO prodrug (Allyloxypolyethyleneglycol‐b‐poly [2‐(((4‐acetyl‐2‐methoxyphenoxy)carbonyl)oxy)ethyl methacrylate], APEG‐PAPO or PAPO) by activated microglia cells. A scar tissue‐homing peptide (cysteine‐alanine‐glutamine‐lysine, CAQK) is introduced to the PAPO to endow the polymer micelle the lesion tissue‐targeting ability. As a result, this CAQK‐modified prodrug micelle (cPAM) exhibits an improved accumulation and prolonged retention in lesion tissue compared to the control micelle. The cPAM also leads to superior tissue protection and sustained motor function recovery than the control groups in a mouse model of SCI. In conclusion, the cPAM induces an effective treatment of SCI by the lesion tissue specific delivery of the prodrug polymer via its robust scar binding effect, making the scar tissue a drug releasing platform for sustained treatment of SCI.

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Section: Resultsmentioning

confidence: 99%

Scar Tissue‐Targeting Polymer Micelle for Spinal Cord Injury Treatment

Wang

Liang

et al. 2020

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“…Qiu et al. also reported another kind of charge‐reversed polymer that is sensitive to intracellular esterases (Figure B) . This esterase‐responsive charge‐reversed polymer (ERP) was a quaternary ammonium‐modified PEI with propionic 4‐acetoxybenzyl ester group.…”

Section: Nanoparticles Used For Nucleic Acid Drug Deliverymentioning

confidence: 99%

“…This esterase‐responsive charge‐reversed polymer (ERP) was a quaternary ammonium‐modified PEI with propionic 4‐acetoxybenzyl ester group. The recovery of carboxylic acid by intracellular esterase ester resulted in charge conversion from cationic to zwitterionic, and the efficient release of packed DNA in fibroblast‐exempt cancer cells was observed . Lipidic ERP (LERP) formed by DC‐chol/DOPE lipids on the surface of ERP polyplexes enabled more efficient condensation of TRAIL plasmid DNA for systemic delivery compared to only PEI/pTRAIL‐treated group, which was beneficial to cytoplasm internalization and lysosome escape.…”

Section: Nanoparticles Used For Nucleic Acid Drug Deliverymentioning

confidence: 99%

Chemical modifications of nucleic acid drugs and their delivery systems for gene‐based therapy

Chen

Yang

Tang

2018

Medicinal Research Reviews

129

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Gene-based therapy is one of essential therapeutic strategies for precision medicine through targeting specific genes in specific cells of target tissues. However, there still exist many problems that need to be solved, such as safety, stability, selectivity, delivery, as well as immunity. Currently, the key challenges of gene-based therapy for clinical potential applications are the safe and effective nucleic acid drugs as well as their safe and efficient gene delivery systems. In this review, we first focus on current nucleic acid drugs and their formulation in clinical trials and on the market, including antisense oligonucleotide, siRNA, aptamer, and plasmid nucleic acid drugs. Subsequently, we summarize different chemical modifications of nucleic acid drugs as well as their delivery systems for gene-based therapeutics in vivo based on nucleic acid chemistry and nanotechnology methods.

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“…[18][19][20][21][22][23] For example, Yuan et al 24 prepared a charge-switchable nanoparticle (S-NP/DOX) based on zwitterionic polymers. The S-NP/DOX remained negative surface charge in the blood circulation system and switched to positive surface charge in response to the tumor acidity; the tumor-acidity-activated charge conversion could effectively increase the cellular uptake of the carriers and the intracellular concentrations of DOX and, in turn, resulted in enhancing tumor inhibitions.…”

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confidence: 99%

pH-triggered surface charge-switchable polymer micelles for the co-delivery of paclitaxel/disulfiram and overcoming multidrug resistance in cancer

Huo¹,

Zhu²,

Niu³

et al. 2017

IJN

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Multidrug resistance (MDR) remains a major challenge for providing effective chemotherapy for many cancer patients. To address this issue, we report an intelligent polymer-based drug co-delivery system which could enhance and accelerate cellular uptake and reverse MDR. The nanodrug delivery systems were constructed by encapsulating disulfiram (DSF), a P-glyco-protein (P-gp) inhibitor, into the hydrophobic core of poly(ethylene glycol)- block -poly( l -lysine) (PEG- b -PLL) block copolymer micelles, as well as 2,3-dimethylmaleic anhydride (DMA) and paclitaxel (PTX) were grafted on the side chain of l -lysine simultaneously. The surface charge of the drug-loaded micelles represents as negative in plasma (pH 7.4), which is helpful to prolong the circulation time, and in a weak acid environment of tumor tissue (pH 6.5–6.8) it can be reversed to positive, which is in favor of their entering into the cancer cells. In addition, the carrier could release DSF and PTX successively inside cells. The results of in vitro studies show that, compared to the control group, the DSF and PTX co-loaded micelles with charge reversal exhibits more effective cellular uptake and significantly increased cytotoxicity of PTX to MCF-7/ADR cells which may be due to the inhibitory effect of DSF on the efflux function of P-gp. Accordingly, such a smart pH-sensitive nanosystem, in our opinion, possesses significant potential to achieve combinational drug delivery and overcome drug resistance in cancer therapy.

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Esterase‐Activated Charge‐Reversal Polymer for Fibroblast‐Exempt Cancer Gene Therapy

Cited by 206 publications

References 52 publications

Scar Tissue‐Targeting Polymer Micelle for Spinal Cord Injury Treatment

Scar Tissue‐Targeting Polymer Micelle for Spinal Cord Injury Treatment

Chemical modifications of nucleic acid drugs and their delivery systems for gene‐based therapy

pH-triggered surface charge-switchable polymer micelles for the co-delivery of paclitaxel/disulfiram and overcoming multidrug resistance in cancer

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