Dual-stimuli-sensitive poly(ortho ester disulfide urethanes)-based nanospheres with rapid intracellular drug release for enhanced chemotherapy

Huang, Yan; Qin, Jiejie; Wang, Jun; Yan, Guoqing; Wang, Xin; Tang, Rupei

doi:10.1007/s11426-018-9269-6

Cited by 9 publications

(3 citation statements)

References 47 publications

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“…So, its application in polymeric micelles is beneficial to the disintegration of micelles in an acidic environment and the drugs release. Although the pH sensitive polymeric micelles containing orthoester can effectively release the drug in response to low pH in the tumor site, it is still difficult to release the drug completely and quickly only with the stimulation of low pH [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Fabrication of pH/Reduction Sensitive Polyethylene Glycol-Based Micelles for Enhanced Intracellular Drug Release

Yang

Shan

et al. 2021

Pharmaceutics

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At present, the drug is still difficult to release completely and quickly only with single stimulation. In order to promote the rapid release of polymeric micelles at tumor site, pH/reduction sensitive polymers (PCT) containing disulfide bonds and orthoester groups were synthesized. The PCT polymers can self-assemble in water and entrap doxorubicin to form drug-loaded micelles (DOX/PCT). In an in vitro drug release experiment, the cumulative release of DOX/PCT micelles in the simulated tumor microenvironment (pH 5.0 with GSH) reached (89.7 ± 11.7)% at 72 h, while it was only (16.7 ± 6.1)% in the normal physiological environment (pH 7.4 without GSH). In addition, pH sensitive DOX loaded micellar system (DOX/PAT) was prepared as a control. Furthermore, compared with DOX/PAT micelles, DOX/PCT micelles showed the stronger cytotoxicity against tumor cells to achieve an effective antitumor effect. After being internalized by clathrin/caveolin-mediated endocytosis and macropinocytosis, DOX/PCT micelles were depolymerized in intercellular acidic and a reductive environment to release DOX rapidly to kill tumor cells. Additionally, DOX/PCT micelles had a better inhibitory effect on tumor growth than DOX/PAT micelles in in vivo antitumor activity studies. Therefore, pH/reduction dual sensitive PCT polymers have great potential to be used as repaid release nanocarriers for intercellular delivery of antitumor drugs.

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Section: Introductionmentioning

confidence: 99%

Fabrication of pH/Reduction Sensitive Polyethylene Glycol-Based Micelles for Enhanced Intracellular Drug Release

Yang

Shan

et al. 2021

Pharmaceutics

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“…Over the past few decades, nanomedicines have attracted much attention to cancer therapy . Nanomedicine delivering active drugs to target site in a solid tumor must go through five steps: circulation in the blood, accumulation in the tumor, penetration deep into the tumor tissue, internalization by cancer cells, and intracellular drug release .…”

Section: Introductionmentioning

confidence: 99%

“…Disulfide bond has been demonstrated to be stable under normal physiological conditions but can be rapidly cleaved in the tumor intracellular high concentration of glutathione (GSH), which is conducive to rapid release of drugs and subsequently improving the antitumor activity . So, this can solve the dilemma between the stability of nanomedicine during blood circulation and intracellular drug release.…”

Section: Introductionmentioning

confidence: 99%

Multi‐Stimuli‐Responsive Polymeric Prodrug for Enhanced Cancer Treatment

Wang

Shen

Sakurai

et al. 2019

Macromolecular Bioscience

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Accomplishing efficient delivery of a nanomedicine to the tumor site will encounter two contradictions as follows: 1) a contradiction between prolonged circulation time and endocytosis by cancer cells; 2) a dilemma between the stability of nanomedicine during blood circulation and intracellular drug release. While developing a nanomedicine which can solve the above two contradictions simultaneously is still a challenge, here, a multi‐stimuli‐responsive polymeric prodrug (PLys‐co‐(PLys‐DA)‐co‐(PLys‐SS‐PTX))‐b‐PLGLAG‐mPEG (P‐PEP‐SS‐PTX‐DA) is synthesized which is multi‐sensitive to overexpressed matrix metalloproteinase‐2 (MMP‐2), low pH, and high concentration of glutathione in tumors. The P‐PEP‐SS‐PTX‐DA can be dePEGylated and reversed from negative at normal physiological pH to positive charge at tumor extracellular microenvironment; in this way, it can solve the contradiction between prolonged circulation time and endocytosis by cancer cells. Owing to the high reductive conditions in cancer cells, P‐PEP‐SS‐PTX‐DA is ruptured to release paclitaxel (PTX) intracellular efficiently; therefore, it can resolve the dilemma between the stability of nanomedicine during blood circulation and intracellular drug release. These indicate that the multi‐stimuli‐responsive polymeric prodrug has potential application prospects in drug delivery and cancer therapy.

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Engineering of a universal polymeric nanoparticle platform to optimize the PEG density for photodynamic therapy

Yang

et al. 2019

Sci. China Chem.

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Dual-stimuli-sensitive poly(ortho ester disulfide urethanes)-based nanospheres with rapid intracellular drug release for enhanced chemotherapy

Cited by 9 publications

References 47 publications

Fabrication of pH/Reduction Sensitive Polyethylene Glycol-Based Micelles for Enhanced Intracellular Drug Release

Fabrication of pH/Reduction Sensitive Polyethylene Glycol-Based Micelles for Enhanced Intracellular Drug Release

Multi‐Stimuli‐Responsive Polymeric Prodrug for Enhanced Cancer Treatment

Engineering of a universal polymeric nanoparticle platform to optimize the PEG density for photodynamic therapy

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