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Introduction to Bioresponsive Polymers
Published in Deepa H. Patel, Bioresponsive Polymers, 2020
Deepa H. Patel, Drashti Pathak, Neelang Trivedi
The ROS mainly target by the oxidation-responsive materials such as hydrogen peroxide (H2O2) and hydroxyl radicals. Sulfur-based materials are the foremost class of oxidation-responsive material. Investigators copolymerized oxidation-convertible poly(propylene sulfide) (PPS) with polyethylene glycol (PEG) to generate amphiphiles capable of self-assembling [18]. Moreover, efficient gene delivery has been accomplished with thioketal-containing materials [19]. Ferrocene-containing materials have also been profoundly explored outstanding to the redox-sensitivity materials [20]. Additionally, initial responsive motifs such as boronic ester groups and phenylboronic acid (PBA) derivatives have also involved significant attention [21–24]. For instance, aryl boronic esters were altered at the hydroxyl groups of dextran as well as the lysine residues of RNase A for H2O2-triggered protein release and action recovery, respectively.
Stimuli-responsive drug delivery systems for head and neck cancer therapy
Published in Drug Delivery, 2021
Jingou Liang, Bina Yang, Xuedong Zhou, Qi Han, Jing Zou, Lei Cheng
More researches were conducted on the intelligent DDSs with combined response to internal and external triggers, since physical exogenous stimuli could be more controllable and flexible. Such dual stimuli-responsive DDSs were widely applied in the phototherapy for HNC. PDT or PTT agents were loaded in pH or MMP sensitive drug carriers for TME controlled drug release and light triggered antitumor treatment (Tarassoli et al., 2017). Meanwhile, chemotherapy agents were also reported co-delivered for the improved chemophoto therapy (Wang, Hu, et al., 2019). Fluorescence dyes could also be co-loaded for simultaneous tumor detection. Furthermore, in view of the ROS generation triggered by light during the PDT for HNC, light and ROS dual responsive DDSs were considered promising in recent researches. Light-responsive agents were loaded in ROS-sensitive carriers, which lead to enhanced ROS generation for PDT and synergistical promotion of drug release combined with endogenous ROS. For instance, Shi et al. (2018) developed ROS-responsive nanoparticles co-loaded with doxorubicin (DOX) and photosensitizer hematoporphyrin for the treatment of oral tongue squamous cell carcinoma. The ROS-induced rupture of thioketal linkage caused the TME-responsive drug release. The DDSs showed significant antitumor effect after laser irradiation. Wang, Zhai, et al. (2019) synthesized ROS-sensitive DDS for OSCC, composed of the self-degrading polymeric carrier and photosensitizer chlorin e6 (Ce6). The significant PDT effect and a cascade reaction for the release of loaded DOX was verified in the research. Another form of light and ROS dual responsive DDS was reported by Huang, Deng, et al. (2019) The nanoplatform was integrated by plasmonic Cu2 − xS and magnetic manganese compounds. The Cu2 − xS core demonstrated PTT and PDT effect under NIR irradiation while the MnS shell showed ROS-responsive O2 production through Fenton-like pathways.
Recent progress in synergistic chemotherapy and phototherapy by targeted drug delivery systems for cancer treatment
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Jie Cao, Zuxian Chen, Jinnan Chi, Yalin Sun, Yong Sun
Since UCNPs are irradiated by NIR light, in the combination therapy, the targeted anticancer drug delivery systems were often designed with on-demand drug release regulated by NIR light [25–30]. Despite an indicator of cancer, intracellular ROS always showed low concentration in cells as well as short lifetime (<0.1 ms), thus it should be more effective to generate ROS in situ using a ROS-sensitive drug-delivery system. One typical example is to introducing a ROS-cleavable linker between the PS and the drug; upon illumination, the generated ROS causes drug release through the cleavage of the linker. Yuan et al. report a novel theranostic platform based on a conjugated-polyelectrolyte (CPE) polyprodrug for chemo and PDT, and on-demand drug release upon light irradiation (Figure 4(A)) [25]. cRGD was modified on the surface of the nanocarrier to enhance the cellular uptake via αvβ3 integrin receptor mediation. The PEGylated CPE not only serves as a carrier, but also as a PDT agent which can generate ROS under irradiation with light. It is covalently conjugated to doxorubicin through a thioketal linker (TL) that can be cleaved by ROS for on-demand drug release and chemotherapy. In vitro cytotoxicity studies showed enhanced cell-viability inhibition for the combined therapy as compared to PDT or chemotherapy alone. Yue et al. developed a thioketal linker-based ROS responsive drug TL-CPT, which conjugated anticancer drug camptothecin with thioketal linker that could be cleaved by ROS (Figure 4(B)) [26]. To achieve cancer synergistic therapy, the photosensitizer Chlorin e6(Ce6), TL-CPT and carboxyl-mPEG were loaded on the upconversion nanoparticles (UCNPs). This nanocarrier could target in vivo lung cancer via EPR effects (enhanced permeability and retention). Upon 980 nm laser irradiation, Ce6 could absorb the light to produce ROS, which was both used for PDT and to cleave the thioketal linker in the resulted drug delivery system to release camptothecin for chemotherapy.
Responsive nanosystems for targeted therapy of ulcerative colitis: Current practices and future perspectives
Published in Drug Delivery, 2023
Min Chen, Huanrong Lan, Ketao Jin, Yun Chen
In the treatment of ulcerative colitis, reactive oxygen species responsive delivery systems have shown promising potentials (Talaei et al. 2013). The imbalance in the production of reactive oxygen species and decrease response of the immune system is referred as oxidative stress that is mainly observed with inflammatory conditions and an over production of reactive oxygen species is observed in ulcerative colitis (Birben et al. 2012; Piechota-Polanczyk and Fichna 2014). The redox – responsive nanosystem takes the advantage of the pathological condition of ulcerative colitis and thus exhibit a profound potential for the therapy of ulcerative colitis. In this regard, TNF – α siRNA loaded thioketal nanoparticles were fabricated for oral administration and targeting of ulcerative colitis. The aim of using thioketal was as a carrier and degradation in response to the reactive oxygen species. Results from murine ulcerative colitis model showed the degradation of the polymer at ulcerative colitis site due to high contents of the reactive oxygen species and efficient delivery of siRNA to protect the mice from ulcerative colitis (Wilson et al. 2010). Similarly, nanoparticles loaded with nitroxide radicals having an amphiphilic block co – polymer was targeted to ulcerative colitis bearing mice and results showed high accumulation of the nitroxide radicals at inflammation site. Mechanistically, the used radicals significantly scavenged reactive oxygen species concluding that nitroxide radicals could be effective therapeutic alternative for ulcerative colitis (Vong et al. 2012). In relationship between reactive oxygen species and ulcerative colitis, luteolin being anti – Inflammatory and ROS scavenging natural flavonoid, was loaded in tocopherol polyethylene glycol succinate – b – poly(β – thioester) copolymer based nanoparticles and targeted to inflamed colon of murine model. Results showed healing of the inflammatory mucosa and resolving inflammation through the suppression of reactive oxygen species and upregulation of anti – inflammatory factors (Tan et al. 2022).