Ligand-targeted cancer therapeutics has been developed to minimize non-specific cytotoxicity via ligand–drug conjugates during the past few decades. We present here the design and synthesis of a GSH-activated amphiphilic photosensitizer conjugated with galactose (TPP-S-S-Gal) for targeted photodynamic therapy. Furthermore, the galactoside photosensitizer as supramolecular amphiphiles can self-assemble into micelles, which can be applied in integrative cancer treatment with chemotherapy drugs such as camptothecin (CPT) encapsulated in the hydrophobic core of micelles. Upon reaction with free thiol GSH that is relatively abundant in tumor cells, disulfide bond cleavage occurs as well as the active photosensitizer TPP and chemotherapy drug CPT release, which can cause cell apoptosis. The in vitro biological assessment of TPP-S-S-Gal micelles against the A549 cell line was evaluated by MTT assay, flow cytometry and confocal scanning laser microscopy, respectively. According to the MTT assay, TPP-S-S-Gal micelles exhibited low dark toxicity and efficient integrative efficacy of PDT and chemotherapy towards A549 cells after light irradiation.
Developing efficient photosensitizers which are sensitive to therapeutic tumor signals, but non-toxic to normal cells has always been a tremendous challenge in photodynamic therapy (PDT) process. Herein, a novel copolymer P1 was developed by ring-opening metathesis polymerization (ROMP) with disulfide bond linked ferrocene-norbornene dyad NB-SS-PyFc and the aggregation-induced emission (AIE) fluorephore anchored norbornene NB-TPE , and its nanoparticles (NPs) were obtained by using the amphiphilic Pluronic F-127 as the surfactant via a nanoprecipitation method. The P1 NPs show a weak emission and a low 1 O 2 generation for the quenching effect from the ferrocene moiety to the AIE group. However, the addition of GSH can recover the AIE fluorephore emission and 1 O 2 generation for cleavage the disulfide bond. Importantly, P1 NPs have been used for image-guided cancer cells apoptosis for the GSH activated 1 O 2 generation.
Yajing Liu,Shaojia Zhu,Kaizhi Gu,Zhiqian Guo,Xiaoyu Huang,Mingwei Wang,Hesham M. Amin,Weihong Zhu,Ping Shi
Theranostic prodrug therapy enables the targeted delivery of anticancer drugs with minimized adverse effects and real-time in situ monitoring of activation of the prodrugs. In this work, we report the synthesis and biological assessment of the near-infrared (NIR) prodrug DCM-S-PPT and its amphiphilic copolymer (mPEG-DSPE)-encapsulated nanoparticles. DCM-S-PPT is composed of podophyllotoxin (PPT) as the anticancer moiety and a dicyanomethylene-4H-pyran (DCM) derivative as the NIR fluorescent reporter, which are linked by a thiol-specific cleavable disulfide bond. In vitro experiments indicated that DCM-S-PPT has low cytotoxicity and that glutathione (GSH) can activate DCM-S-PPT resulting in PPT release and a concomitant significant enhancement in NIR fluorescence at 665 nm. After being intravenously injected into tumor-bearing nude mice, DCM-S-PPT exhibited excellent tumor-activated performance. Furthermore, we have demonstrated that mPEG-DSPE as a nanocarrier loaded with DCM-S-PPT (mPEG-DSPE/DCM-S-PPT) showed even greater tumor-targeting performance than DCM-S-PPT on account of the enhanced permeability and retention effect. Its tumor-targeting ability and specific drug release in tumors make DCM-S-PPT a promising prodrug that could provide a significant strategy for theranostic drug delivery systems.
Min Liu,Hongshuai Wu,Senlin Wang,Jinzhong Hu,Baiwang Sun
The integration of metal-ion therapy and hydroxyl radical (˙OH)-mediated chemodynamic therapy (CDT) holds great potential for anticancer treatment with high specificity and efficiency. Herein, Ag nanoparticles (Ag NPs) were enveloped with Cu2+-based metal–organic frameworks (MOFs) and further decorated with hyaluronic acid (HA) to construct a glutathione (GSH)-activated nanoplatform (Ag@HKU-HA) for specific chemodynamic/metal-ion therapy. The obtained nanoplatform could avoid the premature leakage of Ag in circulation, but realize the release of Ag at the tumor site owing to the degradation of external MOFs triggered by Cu2+-reduced glutathione. The generated Cu+ could catalyze endogenous H2O2 to the highly toxic ˙OH by a Fenton-like reaction. Meanwhile, Ag NPs were oxidized to toxic Ag ions in the tumor environment. As expect, the effect of CDT combined with metal-ion therapy exhibited an excellent inhibition of tumor cells growth. Therefore, this nanoplatform may provide a promising strategy for on-demand site-specific cancer combination treatment.
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