Dataset Information

Paclitaxel-loaded ROS-responsive nanoparticles for head and neck cancer therapy.

ABSTRACT: High intracellular reactive oxygen species (ROS) level is characteristic of cancer cells and could act as a target for the efficient targeted drug delivery for cancer treatment. Consequently, biomaterials that react to excessive levels of ROS are essential for biomedical applications. In this study, a novel ROS-responsive polymer based on D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) and poly (β-thioester) (TPGS-PBTE) was synthesized for targeted delivery of the first-line antineoplastic drug, paclitaxel (PTX). The resultant TPGS-PBTE NPs showed good ROS-responsive capability in size change and drug release. Compared to PTX, PTX-loaded nanoparticles (PTX@TPGS-PBTE NPs) showed enhanced cytotoxicity and higher level of apoptosis toward squamous cell carcinoma (SCC-7) cells. Tumor-targeted delivery of the NPs was also observed, especially after being modified with a tumor-targeting peptide, cRGD. Enhanced tumor growth inhibition was also observed in head and neck cancer SCC-7 murine models. In summary, PTX@TPGS-PBTE NPs can achieve good therapeutic effects of PTX against head and neck cancer both in vitro and in vivo, especially when modified by cRGD for active targeting, which enriched the application of ROS responsive system utilized in the delivery of anticancer drugs.

SUBMITTER: Tu Y

PROVIDER: S-EPMC10026753 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Paclitaxel-loaded ROS-responsive nanoparticles for head and neck cancer therapy.

Tu Yaqin Y Zhang Wei W Fan Guorun G Zou Chenming C Zhang Jie J Wu Nan N Ding Jiahui J Zou Wen Qing WQ Xiao Hongjun H Tan Songwei S

Drug delivery 20231201 1

High intracellular reactive oxygen species (ROS) level is characteristic of cancer cells and could act as a target for the efficient targeted drug delivery for cancer treatment. Consequently, biomaterials that react to excessive levels of ROS are essential for biomedical applications. In this study, a novel ROS-responsive polymer based on D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) and poly (β-thioester) (TPGS-PBTE) was synthesized for targeted delivery of the first-line antineoplas ...[more]

PMID: 36916054

Similar Datasets

Project description:The narrow therapeutic index and significant potential for toxicity of chemotherapeutic drugs are two of the factors that restrict their use. Because of the usage of nanoparticles (NPs) as carriers for chemotherapeutic agents, the therapeutic efficacy of these treatments has been significantly boosted. This was accomplished by increasing the bioavailability of the pharmaceuticals and changing the bio-distribution profile of the drugs. Untargeted metabolomics has recently risen to the forefront as a potentially useful method for better comprehending the growth of tumours and the treatment outcomes of many kinds of cancer cells. In the current study, we used LCMS/MS-based untargeted metabolomics to identify differences in the metabolic profile of head and neck squamous cell carcinomas FaDu that were treated with the anticancer drug paclitaxel (PTX) delivered as free drug versus paclitaxel-loaded poly(lactide-co-glycolide) nanoparticles (PXT-PLGA-NPs). The experimental design consisted of four groups: those treated with DMSO (serving as a control), those treated with drug-free PXT, those treated with PXT-PLGA-NPs, and those treated with PLGA-NPs that lacked PTX. MetaboScape (V4, Bruker Daltonics) was used as the platform for the data analysis, and the results were compared to the Bruker Human Metabolome Data Base (HMDB) spectrum library 2.0. We found a total of 162 metabolites with a high level of confidence ascribed to them. The principal component analysis of the metabolites showed that PTX-free drugs grouped along with PXT-PLGA-NPs, but the control and PLGA-NPs without PXT clustered apart from drug-treated cells but together with each other. In further group pairwise comparisons, it was shown that 37 metabolites were substantially dysregulated (p 0.05) between the PTX-free medication and the PXT-PLGA-NPs. Out of these, it is important to call attention to the metabolites that became more abundant as a result of treatment with PXT-PLGA-NPs. These include 5-Thymidyclic acid with a 7.8-fold change (FC) and 3,4,5-Trimethoxycinnamic acid, both of which have been linked in the past to effective anticancer drug treatment (Quinn et al. 2015; Anantharaju et al. 2017). The findings suggest a more successful anti-drug therapy that makes use of NP, and also indicate a number of metabolites that have the potential to serve as indicators for determining how well an antidrug treatment is working. Our previous findings are consistent with these findings.

Project description:Background:Melanoma is the most common symptom of aggressive skin cancer, and it has become a serious health concern worldwide in recent years. The metastasis rate of malignant melanoma remains high, and it is highly difficult to cure with the currently available treatment options. Effective yet safe therapeutic options are still lacking. Alternative treatment options are in great demand to improve the therapeutic outcome against advanced melanoma. This study aimed to develop albumin nanoparticles (ANPs) coated with macrophage plasma membranes (RANPs) loaded with paclitaxel (PTX) to achieve targeted therapy against malignant melanoma. Methods:Membrane derivations were achieved by using a combination of hypotonic lysis, mechanical membrane fragmentation, and differential centrifugation to empty the harvested cells of their intracellular contents. The collected membrane was then physically extruded through a 400 nm porous polycarbonate membrane to form macrophage cell membrane vesicles. Albumin nanoparticles were prepared through a well-studied nanoprecipitation process. At last, the two components were then coextruded through a 200 nm porous polycarbonate membrane. Results:Using paclitaxel as the model drug, PTX-loaded RANPs displayed significantly enhanced cytotoxicity and apoptosis rates compared to albumin nanoparticles without membrane coating in the murine melanoma cell line B16F10. RANPs also exhibited significantly higher internalization efficiency in B16F10 cells than albumin nanoparticles without a membrane coating. Next, a B16F10 tumor xenograft mouse model was established to explore the biodistribution profiles of RANPs, which showed prolonged blood circulation and selective accumulation at the tumor site. PTX-loaded RANPs also demonstrated greatly improved antitumor efficacy in B16F10 tumor-bearing mouse xenografts. Conclusion:Albumin-based nanoscale delivery systems coated with macrophage plasma membranes offer a highly promising approach to achieve tumor-targeted therapy following systemic administration.

Project description:Melanoma is the most aggressive and metastasis-prone form of skin cancer. Conventional therapies include chemotherapeutic agents, either as small molecules or carried by FDA-approved nanostructures. However, systemic toxicity and side effects still remain as major drawbacks. With the advancement of nanomedicine, new delivery strategies emerge at a regular pace, aiming to overcome these challenges. Stimulus-responsive drug delivery systems might considerably reduce systemic toxicity and side-effects by limiting drug release to the affected area. Herein, we report the development of paclitaxel-loaded lipid-coated manganese ferrite magnetic nanoparticles (PTX-LMNP) as magnetosomes synthetic analogs, envisaging the combined chemo-magnetic hyperthermia treatment of melanoma. PTX-LMNP physicochemical properties were verified, including their shape, size, crystallinity, FTIR spectrum, magnetization profile, and temperature profile under magnetic hyperthermia (MHT). Their diffusion in porcine ear skin (a model for human skin) was investigated after intradermal administration via fluorescence microscopy. Cumulative PTX release kinetics under different temperatures, either preceded or not by MHT, were assessed. Intrinsic cytotoxicity against B16F10 cells was determined via neutral red uptake assay after 48 h of incubation (long-term assay), as well as B16F10 cells viability after 1 h of incubation (short-term assay), followed by MHT. PTX-LMNP-mediated MHT triggers PTX release, allowing its thermal-modulated local delivery to diseased sites, within short timeframes. Moreover, half-maximal PTX inhibitory concentration (IC50) could be significantly reduced relatively to free PTX (142,500×) and Taxol® (340×). Therefore, the dual chemo-MHT therapy mediated by intratumorally injected PTX-LMNP stands out as a promising alternative to efficiently deliver PTX to melanoma cells, consequently reducing systemic side effects commonly associated with conventional chemotherapies.

Dataset Information

Paclitaxel-loaded ROS-responsive nanoparticles for head and neck cancer therapy.

Publications

Paclitaxel-loaded ROS-responsive nanoparticles for head and neck cancer therapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets