Self-Strengthened Oxidation-Responsive Bioactivating Prodrug Nanosystem with Sequential and Synergistically Facilitated Drug Release for Treatment of Breast Cancer

Wang, Kaiyuan; Yang, Bin; Hao, Yue; Zhang, Xuanbo; Song, Hang; Wang, Xia; Li, Na; Wei, Lin; Wang, Yu; Zhang, Haotian; Kan, Qiming; Zhang, He; Wang, Dun; Sun, Jin

doi:10.1021/acsami.9b03056

Cited by 40 publications

(33 citation statements)

References 24 publications

(37 reference statements)

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“…There has been reported that the thioether linkage could be activated by ROS and GSH 29 , 30 , 31 , 32 . Thus, the in vitro drug release of PSD LPs was investigated under the condition of PBS (pH 7.4) containing 15% ethanol ( v / v ) and 10 mmol/L EDTA, with 10 mmol/L H 2 O 2 or 10 mmol/L DTT or 0 mmol/L H 2 O 2 /DTT.…”

Section: Resultsmentioning

confidence: 99%

Remote loading paclitaxel–doxorubicin prodrug into liposomes for cancer combination therapy

Wang

Zhou

et al. 2020

Acta Pharmaceutica Sinica B

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The combination of paclitaxel (PTX) and doxorubicin (DOX) has been widely used in the clinic. However, it remains unsatisfied due to the generation of severe toxicity. Previously, we have successfully synthesized a prodrug PTX- S -DOX (PSD). The prodrug displayed comparable in vitro cytotoxicity compared with the mixture of free PTX and DOX. Thus, we speculated that it could be promising to improve the anti-cancer effect and reduce adverse effects by improving the pharmacokinetics behavior of PSD and enhancing tumor accumulation. Due to the fact that copper ions (Cu 2+ ) could coordinate with the anthracene nucleus of DOX, we speculate that the prodrug PSD could be actively loaded into liposomes by Cu 2+ gradient. Hence, we designed a remote loading liposomal formulation of PSD (PSD LPs) for combination chemotherapy. The prepared PSD LPs displayed extended blood circulation, improved tumor accumulation, and more significant anti-tumor efficacy compared with PSD NPs. Furthermore, PSD LPs exhibited reduced cardiotoxicity and kidney damage compared with the physical mixture of Taxol and Doxil, indicating better safety. Therefore, this novel nano-platform provides a strategy to deliver doxorubicin with other poorly soluble antineoplastic drugs for combination therapy with high efficacy and low toxicity.

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Section: Resultsmentioning

confidence: 99%

Remote loading paclitaxel–doxorubicin prodrug into liposomes for cancer combination therapy

Wang

Zhou

et al. 2020

Acta Pharmaceutica Sinica B

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“…In another study by Wang et al, nanoparticles (LPC/PTX-S-LA PMs) with oxidation-responsive thioether-linked linoleic acid PTX conjugates (PTX-S-LA) and β-lapachone enclosed in PEG-b-poly(d,llactic acid) (PEG-PDLLA) as a ROS-responsive drug delivery system were used [37,[152][153][154]. Likewise, β-lapachone increases ROS, and PTX is released from PTX-S-LA, which effectively acts on cancer cells (Figure 7).…”

Section: Sequential Drug Release Where One Of the Co-loaded Drugs Ampmentioning

confidence: 99%

Recent Advances and Challenges in Controlling the Spatiotemporal Release of Combinatorial Anticancer Drugs from Nanoparticles

et al. 2020

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To overcome cancer, various chemotherapeutic studies are in progress; among these, studies on nano-formulated combinatorial drugs (NFCDs) are being actively pursued. NFCDs function via a fusion technology that includes a drug delivery system using nanoparticles as a carrier and a combinatorial drug therapy using two or more drugs. It not only includes the advantages of these two technologies, such as ensuring stability of drugs, selectively transporting drugs to cancer cells, and synergistic effects of two or more drugs, but also has the additional benefit of enabling the spatiotemporal and controlled release of drugs. This spatial and temporal drug release from NFCDs depends on the application of nanotechnology and the composition of the combination drug. In this review, recent advances and challenges in the control of spatiotemporal drug release from NFCDs are provided. To this end, the types of combinatorial drug release for various NFCDs are classified in terms of time and space, and the detailed programming techniques used for this are described. In addition, the advantages of the time and space differences in drug release in terms of anticancer efficacy are introduced in depth.

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“…NQO1 is overexpressed in numerous solid tumors, such as breast, colon, and lung cancers, by up to 100-fold (Ye et al., 2017 ). Beta-lapachone (Lapa), a substrate of NQO1, is extracted from the bark of the lapacho tree (Siegel et al., 2012 ; Wang et al., 2019 ). Lapa is reduced to an unstable hydroquinone through the activity of NQO1, and is rapidly oxidized back to the parent quinone in the presence of molecular oxygen (Siegel et al., 2012 ; Wang et al., 2019 ).…”

Section: Introductionmentioning

confidence: 99%

“…Beta-lapachone (Lapa), a substrate of NQO1, is extracted from the bark of the lapacho tree (Siegel et al., 2012 ; Wang et al., 2019 ). Lapa is reduced to an unstable hydroquinone through the activity of NQO1, and is rapidly oxidized back to the parent quinone in the presence of molecular oxygen (Siegel et al., 2012 ; Wang et al., 2019 ). This redox cycling can generate high concentrations of ROS, and, because the NQO1 enzyme is not involved in the oxidation reaction, ROS is continuously generated to trigger drug release (Li et al., 2019 ).…”

Section: Introductionmentioning

confidence: 99%

A pH/ROS cascade-responsive and self-accelerating drug release nanosystem for the targeted treatment of multi-drug-resistant colon cancer

Chang

Zhao

et al. 2020

Drug Delivery

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The efficacy of chemotherapeutic agents for colon cancer treatment is limited by multidrug resistance (MDR) and insufficient intracellular release of the administered nanomedicine. To overcome these limitations, we constructed a pH/ROS cascade-responsive and self-accelerating drug release nanoparticle system (PLP-NPs) for the treatment of multidrug-resistant colon cancer. The PLP-NPs comprised a reactive oxygen species (ROS)-sensitive polymeric paclitaxel (PTX) prodrug (DEX-TK-PTX), a pH-sensitive poly(L-histidine) (PHis), and beta-lapachone (Lapa), a ROS-generating agent. We found that PLP-NPs could accumulate in tumor tissue through enhancement of the permeability and retention (EPR) effect, and were subsequently internalized by cancer cells via the endocytic pathway. Within the acidic endolysosomal environment, PHis protonation facilitated the escape of the PLP-NPs from the lysosome and release of Lapa. The released Lapa generated a large amount of ROS, consumed ATP, and downregulated P-glycoprotein (P-gp) production through the activity of NQO1, an enzyme that is specifically overexpressed in tumor cells. In addition, the generated ROS promoted the release of PTX from DEX-TK-PTX to kill cancer cells, while ATP depletion inhibited P-gp-mediated MDR. In vitro and in vivo experiments subsequently confirmed that PLP-NPs induced tumor-specific cytotoxicity and overcame the MDR of colon cancer. Our findings indicate that the use of the PLP-NPs system represents a promising strategy to counter MDR in the treatment of colon cancer.

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Self-Strengthened Oxidation-Responsive Bioactivating Prodrug Nanosystem with Sequential and Synergistically Facilitated Drug Release for Treatment of Breast Cancer

Cited by 40 publications

References 24 publications

Remote loading paclitaxel–doxorubicin prodrug into liposomes for cancer combination therapy

Remote loading paclitaxel–doxorubicin prodrug into liposomes for cancer combination therapy

Recent Advances and Challenges in Controlling the Spatiotemporal Release of Combinatorial Anticancer Drugs from Nanoparticles

A pH/ROS cascade-responsive and self-accelerating drug release nanosystem for the targeted treatment of multi-drug-resistant colon cancer

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