Smart pH-sensitive micelles based on redox degradable polymers as DOX/GNPs carriers for controlled drug release and CT imaging

Xiong, Di; Zhang, Xiaofang; Peng, Shiyuan; Gu, Huawei; Zhang, Lijuan

doi:10.1016/j.colsurfb.2017.12.008

Cited by 60 publications

(35 citation statements)

References 75 publications

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“…To obtain greater specificity and efficacy, the various stimuli responsive drug delivery system discussed above were often used in combinations. Xiong et al [ 60 ] have reported the synthesis of pH/redox sensitive micelles for the delivery of DOX and gold nanoparticles (GNPs). The micelles comprise of an amphiphilic copolymer of poly(ε-caprolactone)-ss-poly(2-(dimethylamino) ethyl methacrylate) (PCL-SS-PDMAEMA).…”

Section: Targeting Of Common Attributes Of Tmementioning

confidence: 99%

Tumor microenvironment-responsive nanoparticles for cancer theragnostic applications

2018

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BackgroundCancer is one of the deadliest threats to human health. Abnormal physiochemical conditions and dysregulated biosynthetic intermediates in the tumor microenvironment (TME) play a significant role in modulating cancer cells to evade or defend conventional anti-cancer therapy such as surgery, chemotherapy and radiotherapy. One of the most important challenges in the development of anti-tumor therapy is the successful delivery of therapeutic and imaging agents specifically to solid tumors.Main bodyThe recent progresses in development of TME responsive nanoparticles offers promising strategies for combating cancer by making use of the common attributes of tumor such as acidic and hypoxic microenvironments. In this review, we discussed the prominent strategies utilized in the development of tumor microenvironment-responsive nanoparticles and mode of release of therapeutic cargo.ConclusionTumor microenvironment-responsive nanoparticles offers a universal approach for anti-cancer therapy.

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Section: Targeting Of Common Attributes Of Tmementioning

confidence: 99%

Tumor microenvironment-responsive nanoparticles for cancer theragnostic applications

2018

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“…PCL 27 -SS-iBuBr and PCL 27 -SS-P(PEGMA 10.2 -co-MAEBA 13.4 ) in our early report [17] were selected and used in this work. The copolymer PCL-SS-PDMAEMA was synthesized according to the other report [34] based on the precursor PCL 27 -SS-iBuBr, which aimed to have the same hydrophobic block with PCL 27 -SS-P(PEGMA 10.2 -co-MAEBA 13.4 ).…”

Section: Synthesis Of the Copolymers Pcl-ss-p(pegma-co-maeba) And Pclmentioning

confidence: 99%

Reversible Cross-Linked Mixed Micelles for pH Triggered Swelling and Redox Triggered Degradation for Enhanced and Controlled Drug Release

et al. 2020

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Good stability and controlled drug release are important properties of polymeric micelles for drug delivery. A good candidate for drug delivery must have outstanding stability in a normal physiological environment, followed with low drug leakage and side effects. Moreover, the chemotherapeutic drug in the micellar core should also be quickly and “on-demand” released in the intracellular microenvironment at the tumor site, which is in favor of overcoming multidrug resistance (MDR) effects of tumor cells. In this work, a mixed micelle was prepared by the simple mix of two amphiphilic copolymers, namely PCL-SS-P(PEGMA-co-MAEBA) and PCL-SS-PDMAEMA, in aqueous solution. In the mixed micelle’s core–shell structure, PCL blocks were used as the hydrophobic core, while the micellar hydrophilic shell consisted of two blocks, namely P(PEGMA-co-MAEBA) and PDMAEMA. In the micellar shell, PEGMA provided hydrophilicity and stability, while MAEBA introduced the aldehyde sites for reversible crosslinking. Meanwhile, the PDMAEMA blocks were also introduced in the micellar shell for pH-responding protonation and swelling of the micelle. The disulfide bonds between the hydrophobic core and hydrophilic shell had redox sensitive properties. Reversible cross-linked micelles (RCLMs) were obtained by crosslinking the micellar shell with an imine structure. RCLMs showed good stability and excellent ability against extensive dilution by aqueous solution. In addition, the stability in different conditions with various pH values and glutathione (GSH) concentrations was studied. Then, the anticancer drug doxorubicin (DOX) was selected as the model drug to evaluate drug entrapment and release capacity of mixed micelles. The in vitro release profiles indicated that this RCLM had controlled drug release. In the simulated normal physiological environment (pH 7.4), the drug release of the RCLMs was restrained obviously, and the cumulative drug release content was only 25.7 during 72 h. When it came to acidic conditions (pH 5.0), de-crosslinking of the micelles occurred, as well as protonation of PDMAEMA blocks and micellar swelling at the same time, which enhanced the drug release to a large extent (81.4%, 72 h). Moreover, the drug release content was promoted further in the presence of the reductant GSH. In the condition of pH 5.0 with 10 mM GSH, disulfide bonds broke-up between the micelle core and shell, followed by shedding of the shell from the inner core. Then, the micellar disassembly (degradation) happened based on the de-crosslinking and swelling, and the drug release was as high as 95.3%. The MTT assay indicated that the CLSMs showed low cytotoxicity and good biocompatibility against the HepG2 cells. In contrast, the DOX-loaded CLSMs could efficiently restrain the proliferation of tumor cells, and the cell viability after 48 h incubation was just 13.2%, which was close to that of free DOX. This reversible cross-linked mixed micelle with pH/redox responsive behaviors is a potential nanocarrier for chemotherapy.

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“…The protonation of ionized groups in polymers at acidic pH was commonly regarded as another effective pH-sensitive strategy [87]. The electrostatic interaction between the copolymer was changed and the hydrophobicity or hydrophilic properties of the polymer block was reversed eventually leading to the disintegration of the PMs when the ionizable groups were protonated in the acidic TME [88][89][90]. For example, Yu et al [91] constructed a novel triple-layered micelle based on PEG, poly(aminolated glycidyl methacrylate)(PAGA) and poly(2-(diisopropyl amino)ethyl methacrylate)(PDPA) for co-delivery siRNA-p65 and cisplatin prodrug, in which the PDPA could undergo protonated at acidic PH.…”

Section: Acid Tumour Microenvironment-responsive Co-delivery Intelligmentioning

confidence: 99%

Intelligent polymeric micelles for multidrug co-delivery and cancer therapy

Ning

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Polymeric micelles (PMs) play a vital role in multidrug co-delivery and cancer treatment. However, development of intelligent PMs further allows PMs to accurately target tumour, selectively release cargo multidrug and increase uptake. Therefore, targets, controlled release and uptake of intelligent PMs should be paid more attention to improvement of synergistic therapeutic outcomes and minimize side effects. In this review, tumour targeting of co-delivery intelligent PMs and its intracellular trafficking mechanisms were overviewed. And this review provides a comprehensive summarization of several intelligent co-delivery PMs. Such a system could control the multidrug to be released simultaneously or sequentially by special properties of tumour microenvironment (TME) (including acidic PH, redox, overexpressed enzyme, excessive temperature) and external environment trigger. Additionally, limitations, clinical translation and future perspectives of intelligent co-delivery PMs were also being discussed in this article.

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Smart pH-sensitive micelles based on redox degradable polymers as DOX/GNPs carriers for controlled drug release and CT imaging

Cited by 60 publications

References 75 publications

Tumor microenvironment-responsive nanoparticles for cancer theragnostic applications

Tumor microenvironment-responsive nanoparticles for cancer theragnostic applications

Reversible Cross-Linked Mixed Micelles for pH Triggered Swelling and Redox Triggered Degradation for Enhanced and Controlled Drug Release

Intelligent polymeric micelles for multidrug co-delivery and cancer therapy

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