A co-delivery system based on a reduction-sensitive polymeric prodrug capable of loading hydrophilic and hydrophobic drugs for combination chemotherapy

Yi, Xiaoqing; Zhao, Dan; Zhang, Quan; Xu, Jiaqi; Gao, Yuan; Zhuo, Ren‐Xi; Li, Feng

doi:10.1039/c6py00900j

Cited by 45 publications

(27 citation statements)

References 42 publications

(38 reference statements)

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“…Drug loading efficiency (DLE) and drug loading content (DLC) were evaluated from the absorption peak intensity at 485 nm of the Dox encapsulated polymers and mapping the values in a calibration curve, generated from the concentration dependent UV/vis spectra of the free drug. In this way the DLE of P1 and P2 were calculated to be 15.3% and 18.4% whereas DLC values were 1.7% and 1.9%, respectively, revealing comparable drug loading efficiencies of both the polymersome and the micelle . Low DLC values compared to those reported in the literature for other amphiphilic polymers (range between 3% and 10% or more) could be a consequence of rather low hydrophilicity of the core containing segmented oligo‐oxyethylene chains.…”

Section: Resultsmentioning

confidence: 68%

Morphology Regulation in Redox Destructible Amphiphilic Block Copolymers and Impact on Intracellular Drug Delivery

Bej

Sarkar

Ray

et al. 2018

Macromolecular Bioscience

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In two ABA type amphiphilic block copolymers (P1, P2), the hydrophobic B block consists of a bioreducible segmented poly(disulfide) (PDS), while poly-N-isopropylacrylamide (PNIPAM) or poly(triethyleneglycol)methylether-methacrylate (PTEGMA) serve as the hydrophilic A blocks in P1 and P2, respectively, leading to the formation of polymersome and micelle, owing to the difference in the packing parameters. Both exhibit comparable doxorubicin (Dox) encapsulation efficiency, but glutathione (GSH) triggered release appears much faster from the polymersome than micelle owing to the complete degradation of the PDS segment in polymersome morphology unlike in micelle. Dox-loaded polymers (P1-Dox and P2-Dox) exhibit minimum toxicity to normal cells like C2C12. By contrast, P1-Dox shows excellent killing efficiency to the HeLa cells (cancer cell) (in which the GSH concentration is significantly higher). However, P2-Dox reveals a rather poor activity even to HeLa cells. Fluorescence microscopy studies show comparable cellular uptake of P1-Dox and P2-Dox. But the polymersome entrapped dye escapes fast from the cargo and reach the nucleus, while the drug-loaded micelle remains trapped in the perinuclear zone explaining the significant difference in the drug delivery performance of polymersome and micelle.

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Section: Resultsmentioning

confidence: 68%

Morphology Regulation in Redox Destructible Amphiphilic Block Copolymers and Impact on Intracellular Drug Delivery

Bej

Sarkar

Ray

et al. 2018

Macromolecular Bioscience

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“…The reduction-sensitive TB@PMP micelles co-deliver paclitaxel and AIEgen photosensitizer combinational image-guided PDT/chemotherapy is consequently achieved. The polymeric prodrug PMP was synthesized according to our previous report 45 , and the partial characterization is shown in Supplementary Figures 1 and 2 . PM and PMP polymeric micelles were prepared by dialysis method, and the critical micelles concentrations (CMC) of PM and PMP were 13.7 and 7.9 mg L −1 , respectively, determined by fluorescence measurement using pyrene as a probe (Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

“…Detailed material information was provided in our previous article 45 . Additionally, FITC Phalloidin, Calcein-AM, 2′,7′-dichlorofluorescin diacetate (DCFH-DA), and Annexin V-FITC were provided by yeasen Co. Ltd. (Shanghai, China).…”

Section: Methodsmentioning

confidence: 99%

A high therapeutic efficacy of polymeric prodrug nano-assembly for a combination of photodynamic therapy and chemotherapy

Dai

Han

et al. 2018

Commun Biol

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Combination of photodynamic therapy and chemotherapy has been emerging as a new strategy for cancer treatment. Conventional photosensitizer tends to aggregate in aqueous media, which causes fluorescence quenching, reduces reactive oxygen species (ROS) production, and limits its clinical application to photodynamic therapy. Traditional nanoparticle drug delivery system for chemotherapy also has its disadvantages, such as low drug loading content, drug leakage, and off-target toxicity for normal tissues. Here, we developed a reduction-sensitive co-delivery micelles TB@PMP for combinational therapy, which composed of entrapping a red aggregation-induced emission fluorogen (AIEgen) for photodynamic therapy and PMP that contains a reduction-sensitive paclitaxel polymeric prodrug for chemotherapy. AIEgen photosensitizer illustrates a much improved photostability and ROS production efficiency in aggregate state and PMP loads a high dose of paclitaxel and carries a smart stimuli-triggered drug release property. This co-delivery system provides a better option that replaces AIEgen photosensitizer for cancer diagnosis and therapy.

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“…The safety of prodrug was determined after 24 and 72 h of incubation with a series of Hep-Chl concentrations (0, 0.2, 0.4, 0.6, 0.8, and 1 mg/mL equivalent concentration of Chl), which revealed no potential cytotoxicity of the Hep-Chl prodrug nanoparticles against HaCaT and RAW264.7 cells at a maximum dose of 1 mg/mL. This may be attributed to the lower level of GSH and H2O2 and thereby insufficient cleavage of Chl from the Hep-Chl prodrug in normal cells [37][38][39][40] (Figure 6). In contrast, the viability of HeLa cells treated with Hep-Chl prodrug nanoparticles with the same concentrations was decreased to 41% at 24 h and 23% at 72 h treatments with increase in concentration ( Figure S4a), which was considerably lower than that of RAW264.7 cells treated with the same concentration of the prodrug ( Figure S4b).…”

Section: In Vitro Cytotoxicity Studymentioning

confidence: 97%

Redox-Responsive Heparin–Chlorambucil Conjugate Polymeric Prodrug for Improved Anti-Tumor Activity

et al. 2019

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Polymeric prodrug-based delivery systems have been extensively studied to find a better solution for the limitations of a single drug and to improve the therapeutic and pharmacodynamics properties of chemotherapeutic agents, which can lead to efficient therapy. In this study, redox-responsive disulfide bond-containing amphiphilic heparin–chlorambucil conjugated polymeric prodrugs were designed and synthesized to enhance anti-tumor activities of chlorambucil. The conjugated prodrug could be self-assembled to form spherical vesicles with 61.33% chlorambucil grafting efficiency. The cell viability test results showed that the prodrug was biocompatible with normal cells (HaCaT) and that it selectively killed tumor cells (HeLa cells). The uptake of prodrugs by HeLa cells increased with time. Therefore, the designed prodrugs can be a better alternative as delivery vehicles for the chlorambucil controlled release in cancer cells.

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A co-delivery system based on a reduction-sensitive polymeric prodrug capable of loading hydrophilic and hydrophobic drugs for combination chemotherapy

Abstract: A reduction-sensitive polymeric prodrug PEG-b-PMPMC-g-PTX was designed. The self-assemblies of polymeric prodrug could deliver drugs with different action mechanisms into tumor cells, leading to the apoptosis of tumor cells effectively.

Cited by 45 publications

References 42 publications

Morphology Regulation in Redox Destructible Amphiphilic Block Copolymers and Impact on Intracellular Drug Delivery

Morphology Regulation in Redox Destructible Amphiphilic Block Copolymers and Impact on Intracellular Drug Delivery

A high therapeutic efficacy of polymeric prodrug nano-assembly for a combination of photodynamic therapy and chemotherapy

Redox-Responsive Heparin–Chlorambucil Conjugate Polymeric Prodrug for Improved Anti-Tumor Activity

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