2023
DOI: 10.7150/thno.78884
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Zwitterionic rhodamine-CPT prodrug nanoparticles with GSH/H2O2 responsiveness for cancer theranostics

Abstract: Rationale: Fluorescently traceable prodrugs, which can monitor their biodistribution in vivo and track the kinetics of drug delivery in living cells, are promising for constructing theranostic medicines. However, due to their charge and hydrophobicity, most of the fluorescently traceable prodrugs exhibit high protein binding and non-specific tissue retention affecting in vivo distribution and toxicity, with high background signals. Methods: Herein, the zwitterionic rhodamine (RhB) and camptothecin (CPT) were b… Show more

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Cited by 8 publications
(3 citation statements)
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“…On the one hand, as the H 2 O 2 solution is acidic and the SA PEI contains a large amount of primary and tertiary amino groups, they could be protonated under acidic conditions and causing the hyperbranched chains of SA PEI to change from a dense state into an absolutely loose state, which could accelerate the drug release. On the other hand, disulfide bonds can be oxidized to hydrophilic sulfoxide or sulfone under the action of H 2 O 2 , thereby promoting the hydrolysis of adjacent ester bonds and realizing the design of H 2 O 2 -responsive drug release.…”
Section: Resultsmentioning
confidence: 99%
“…On the one hand, as the H 2 O 2 solution is acidic and the SA PEI contains a large amount of primary and tertiary amino groups, they could be protonated under acidic conditions and causing the hyperbranched chains of SA PEI to change from a dense state into an absolutely loose state, which could accelerate the drug release. On the other hand, disulfide bonds can be oxidized to hydrophilic sulfoxide or sulfone under the action of H 2 O 2 , thereby promoting the hydrolysis of adjacent ester bonds and realizing the design of H 2 O 2 -responsive drug release.…”
Section: Resultsmentioning
confidence: 99%
“…Interestingly, the responsiveness of the nanomedicine towards both H2O2 and GSH was verified with a rapid fluorescence enhancement was observed at the condition of ≥ 100 mM H 2 O 2 and ≥ 10 mM GSH. With the aid of this redox-cleavable linkage, a high tumor inhibition rate of 77.4% was achieved in comparison with 51.2% in the free CPT-treated group, meanwhile, the highest fluorescence intensity was found at tumor sites at 12 h post-injection [150]. In another report, a ROSactivatable chemotheranostic prodrug nanomedicine (Bio-(8)-MB-CPT) was developed by conjugating a ROS-responsive leucomethylene (LMB) derivative to a self-immolative space-containing biotin-camptothecin conjugate.…”
Section: Redox-activatable Theranostic Nanomedicinementioning
confidence: 95%
“…Prohibitin-1 (PHB1) is one of the two highly homologous subunits of the eukaryotic mitochondrial PHB complex, and its overexpression promotes the development of chemotherapy resistance of lung cancer. Therefore, the combination of small-interfering RNA (siPHB1) to downregulate the expression of PHB1 protein , and CPT is a feasible method for lung cancer therapy. Different from normal cells, the specific features of the tumor microenvironment (TME), including low pH, elevated temperature, an overexpressed enzyme, an abnormal level of reactive oxygen species (ROS), reductions, etc ., have been intensively utilized to trigger the release of anticancer drug and/or genes from their nanocarriers. Among them, both high levels of ROS and reductive glutathione (GSH) have attracted much attention due to the rapid proliferation of tumor cells; therefore, ROS and GSH are considered sequential triggers for constructing dual-responsive nanocarriers. Xiao et al designed a ROS/GSH dual-responsive nanoplatform for codelivery of paclitaxel (PTX) and photosensitizer purpurin 18 (P18); this chemo-photodynamic therapy induced synergistic anticancer and improved immune checkpoint blockade (ICB) efficiency . However, the lack of rational design of a biosafety structure and premature leakage of the “cargo” during circulation are the problems still faced by multiple stimulus-responsive systems for cancer therapy. …”
Section: Introductionmentioning
confidence: 99%