Photoinduced Electron Transfer-Based Glutathione-Sensing Theranostic Nanoprodrug with Self-Tracking and Real-Time Drug Release Monitoring for Cancer Treatment.

The rapid development of nanomedicine has considerably advanced precision therapy for cancer treatment. Superior to traditional chemotherapy, emerging theranostic nanoprodrugs can effectively realize inherent self-tracking, targeted drug delivery, stimuli-triggered drug release, and reduced systemic toxicity of chemotherapeutic drugs. However, theranostic nanoprodrugs with real-time drug release monitoring have remained rare so far. In this work, we developed a new glutathione-responsive theranostic nanoprodrug with a high drug-loading content of 59.4 wt % and an average nanoscale size of 46 nm, consisting of the anticancer drug paclitaxel and a fluorescent imaging probe with a high fluorescence quantum yield, which are linked by a disulfide-based glutathione-sensitive self-immolating linker. The strong fluorescence emission of the fluorophore enables efficacious self-tracking and sensitive fluorescence "ON-OFF" glutathione sensing. Upon encountering high-level glutathione in cancer cells, the disulfide bond is cleaved, and the resulting linker halves spontaneously collapse into cyclic small molecules at the same pace, leading to the simultaneous release of the therapeutic drug and the fluorescence-OFF imaging probe. Thereby, the drug release process is efficiently monitored by the fluorescence change in the nanoprodrug. The nanoprodrugs exerted high cytotoxicity toward various cancer cells, especially for A549 and HEK-293 cells, in which the nanoprodrugs generated better therapeutic effects than free paclitaxel. Our work demonstrated a new modality of smart theranostic nanoprodrugs for precise cancer therapy.

Injectable, Self-Healing, and Biocompatible N,O-Carboxymethyl Chitosan/Multialdehyde Guar Gum Hydrogels for Sustained Anticancer Drug Delivery.

Local delivery of anticancer agents via injectable hydrogels could be a promising method for achieving spatiotemporal control on drug release as well as minimizing the disadvantages related to the systemic mode of drug delivery. Keeping this in mind, we report the development of N,O-carboxymethyl chitosan (N,O-CMCS)-guar gum-based injectable hydrogels for the sustained delivery of anticancer drugs. The hydrogels were synthesized by chemical crosslinking of multialdehyde guar gum (MAGG) and N,O-CMCS through dynamic Schiff base linkages, without requiring any external crosslinker. Fabrication of injectable hydrogels, involving N,O-CMCS and MAGG via Schiff base crosslinking, is being reported for the first time. The hydrogels exhibited pH-responsive swelling behavior and good mechanical properties with a storage modulus of about 1625 Pa. Due to the reversible nature of Schiff base linkages, hydrogels displayed excellent self-healing and thixotropic properties. Doxorubicin (Dox), an anticancer agent, was loaded onto these hydrogels and its release studies were conducted at pH 7.4 (physiological) and pH 5.5 (tumoral). A sustained release of about 67.06% Dox was observed from the hydrogel after 5 days at pH 5.5 and about 32.13% at pH 7.4. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay on the human embryonic kidney cell line (HEK-293) and the hemolytic assay demonstrated the biocompatible nature of the hydrogels. The Dox-loaded hydrogel exhibited a significant killing effect against breast cancer cells (MCF-7) with a cytotoxicity of about 72.13%. All the data presented support the efficiency of the synthesized N,O-CMCS/MAGG hydrogel as a biomaterial that may find promising applications in anticancer drug delivery.

γ-Radiation induced L-glutamic acid grafted highly porous, pH-responsive chitosan hydrogel beads: A smart and biocompatible vehicle for controlled anti-cancer drug delivery.

In the present work, highly porous, pH-responsive, and biocompatible chitosan-based hydrogel beads were prepared through gamma-irradiated graft copolymerization technique using L-glutamic acid as the monomer. The glutamic acid grafted chitosan (CH-g-GA) hydrogel beads, loaded with the anti-cancer drug (Doxorubicin, Dox), were exploited for their potential application as anti-cancer drug delivery system. The grafting conditions were optimized by varying irradiation dose (kGy) and monomer concentration. Further, the hydrogel beads were analysed using FTIR, XRD, SEM, TGA/DSC, Zeta potential studies, BET analysis and their strength was determined using rheological analysis. The swelling characteristics of the beads were studied at various simulated body pH (2.1, 5.8, and 7.4) to study their pH-responsive behaviour. The in-vitro drug release from the beads was thus evaluated at pH 5.8, 7.4 using UV-visible spectroscopy. The highest swelling ratio (426%) and drug release (81.33% in 144 h) was observed at the pH of 5.8. The MTT assay was performed on HEK-293 cell-line to check their cytocompatibilty and the cell proliferation of Dox-loaded beads was studied on MCF-7 cell-line. A significant cytotoxicity against the cancer-cells was observed which further established their promising use in the controlled delivery of anti-cancer agents for localized cancer therapy.