Charge-conversional zwitterionic copolymer as pH-sensitive shielding system for effective tumor treatment

Chen, Jie; Dong, Xuan; Feng, Tianshi; Lin, Lin; Guo, Zhaopei; Xia, Jiangzhou; Tian, Huayu; Chen, Xuesi

doi:10.1016/j.actbio.2015.08.018

Cited by 57 publications

(41 citation statements)

References 28 publications

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“…Chen et al . reported a zwitterionic copolymer OEAL that can change surface charges from negative to positive in the pH range 7.4–6.8.…”

Section: Carriers Regulated By the Tumor Microenvironmentmentioning

confidence: 99%

“…Guan et al 23 developed an ultrasensitive charge/size dual-rebound Chen et al 38 reported a zwitterionic copolymer OEAL that can change surface charges from negative to positive in the pH range 7.4-6.8. The copolymer consists of poly(L-aspartate), poly(L-lysine) and oligoethylenimine and can be used as a shielding layer for PEIbased gene delivery.…”

Section: Ph-responsive Gene Carriersmentioning

confidence: 99%

“…80,81 Introducing specific programmed cell death gene in tumor cells is a common method in cancer gene therapy. 38,[82][83][84] Canonical cancer gene therapies usually focus on proteins or genes that influence tumor apoptosis, such as caspase-3, p53 and Bcl2.…”

Section: Targeting Tumor Cellsmentioning

confidence: 99%

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Tumor microenvironment as the “regulator” and “target” for gene therapy

Chen

Feng

et al. 2019

The Journal of Gene Medicine

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In this review, we focus on strategies for designing functional nano gene carriers, as well as choosing therapeutic genes targeting the tumor microenvironment. Gene mutations have a great impact on the occurrence of cancer. Thus, gene therapy plays a major role in cancer therapy and has the potential to cure cancer. Well‐designed gene therapy largely relies on effective gene carriers, which can be divided into viral carriers and non‐viral carriers. A gene carrier delivers functional genes to their intracellular target and avoids nucleic acids being degraded by nucleases in the serum. Most conventional cancer gene therapies only target cancer cells and do not appear to be sufficintly efficient to pass clinical trials. Accumulating evidence has shown that extending the therapeutic strategies to the tumor microenvironment, rather than the tumor cell itself, can allow more options for achieving robust anti‐cancer efficiency. In addition, unusual features between tumor microenvironment and normal tissues, such as a lower pH, higher glutathione and reactive oxygen species concentrations, and overexpression of some enzymes, facilitate the design of smart stimuli‐responsive gene carriers regulated by the tumor microenvironment. These carriers interact with nucleic acids and then form stable nanoparticles under physiological conditions. By regulation of the tumor microenvironment, stimuli‐responsive gene carriers are able to change their properties and achieve high gene delivery efficiency. Considering the tumor microenvironment as the “regulator” and “target” when designing gene carriers and choosing therapeutic genes shows significant benefit with respect to improving the accuracy and efficiency of cancer gene therapy.

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“…Chen et al . reported a zwitterionic copolymer OEAL that can change surface charges from negative to positive in the pH range 7.4–6.8.…”

Section: Carriers Regulated By the Tumor Microenvironmentmentioning

confidence: 99%

Section: Ph-responsive Gene Carriersmentioning

confidence: 99%

See 1 more Smart Citation

Tumor microenvironment as the “regulator” and “target” for gene therapy

Chen

Feng

et al. 2019

The Journal of Gene Medicine

Self Cite

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“…28–38 Nevertheless, as chemistries and products are being made available to wider audiences, the risk exists that these polymers are also formulated into everyday products thus leading to generation of acquired immunity against them. Furthermore, as pointed out above, the risk also exists that patients could develop antibodies after repeated exposure, as has been observed for PEG.…”

Section: Peg and Other Synthetic Polymeric Shielding Strategiesmentioning

confidence: 99%

Bioinspired Shielding Strategies for Nanoparticle Drug Delivery Applications

Gulati

Stewart²,

Steinmetz³

2018

Mol. Pharmaceutics

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Nanoparticle delivery systems offer advantages over free drugs, in that they increase solubility and biocompatibility. Nanoparticles can deliver a high payload of therapeutic molecules while limiting off target side effects. Therefore, delivery of an existing drug with a nanoparticle frequently results in an increased therapeutic index. Whether of synthetic or biologic origin, nanoparticle surface coatings are often required to reduce immune clearance and thereby increase circulation times allowing the carriers to reach their target site. To this end, polyethylene glycol (PEG) has long been used, with several PEGylated products reaching clinical use. Unfortunately, the growing use of PEG in consumer products has led to an increasing prevalence of PEG-specific antibodies in the human population, which in turn has fueled the search for alternative coating strategies. This review highlights alternative bio-inspired nanoparticle shielding strategies, which may be more beneficial moving forward than PEG and other synthetic polymer coatings.

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“…[9,10] Based on the weakly acidic environmento ft umor tissues compared with normalp hysiological conditions, [11][12][13] various pH-responsive drug carriers have been developed to produce high intracellular drug release, such as liposomes, polymeric micelles,polymers, dendrimers, and organic/inorganic NPs. [14][15][16][17][18][19][20] Of these pH-responsive drug carriers,t he development of CaPbased nanocarriers has shown that they are potentialc andidates for intracellular drug delivery because CaP remains stable at physiologicalpH, but dissolves rapidly in an acidic endosomal( pH 5.0) or lysosomal (pH 4.5) environment, which leads to fast releaseo fa nticancerd rugs. [21] Moreover,a s am ajor component of bones and teeth, CaP exhibits extraordinary biocompatibility,s uperiorb iodegradability,a nd is nontoxic, [22,23] which makes it suitable for drug delivery.T od ate, researches have reported the use of organic amphiphilic polymers,d endrimers, or adenosine 5'-triphosphate as templates for CaP-based nanocarriers [24][25][26][27][28] to avoid the problemsa ssociated with the direct synthesis CaP NPs.…”

Section: Introductionmentioning

confidence: 99%

Designed Synthesis of Lipid‐Coated Polyacrylic Acid/Calcium Phosphate Nanoparticles as Dual pH‐Responsive Drug‐Delivery Vehicles for Cancer Chemotherapy

Wang

Zhang

et al. 2017

Chemistry A European J

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Herein, we report a facile strategy to prepare supported lipid-bilayer-coated polyacrylic acid/calcium phosphate nanoparticles (designated as PAA/CaP@SLB NPs) as a new dual pH-responsive drug-delivery platform for cancer chemotherapy. The synthesized PAA/CaP NPs exhibited both a high payload of doxorubicin (DOX) and dual pH-responsive drug-release properties. Additionally, the coated lipid bilayer had the ability to enhance the cellular uptake of PAA/CaP NPs without affecting the pH-responsive drug release. Moreover, the blank PAA/CaP@SLB NPs exhibited excellent biocompatibility and the DOX-loaded PAA/CaP@SLB NPs markedly increased the cellular accumulation of DOX and its cytotoxic effects on HepG-2 cells. Furthermore, when used to evaluate the in vivo therapeutic efficacy in mice with the hepatocarcinoma cell line (H-22), the DOX-loaded PAA/CaP@SLB NPs exhibited superior inhibition of tumor growth compared with the free DOX group. Thus, PAA/CaP@SLB NPs are a promising drug-delivery vehicle to increase the therapeutic efficacy of anticancer drugs.

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Charge-conversional zwitterionic copolymer as pH-sensitive shielding system for effective tumor treatment

Cited by 57 publications

References 28 publications

Tumor microenvironment as the “regulator” and “target” for gene therapy

Tumor microenvironment as the “regulator” and “target” for gene therapy

Bioinspired Shielding Strategies for Nanoparticle Drug Delivery Applications

Designed Synthesis of Lipid‐Coated Polyacrylic Acid/Calcium Phosphate Nanoparticles as Dual pH‐Responsive Drug‐Delivery Vehicles for Cancer Chemotherapy

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