Mitochondria-Targeting Polymer Micelles in Stepwise Response Releasing Gemcitabine and Destroying the Mitochondria and Nucleus for Combined Antitumor Chemotherapy

Zhang, Shanming; Zheng, Fang; Liu, Kaige; Liu, Shengke; Xiao, Tonghu; Zhu, Yabin; Xu, Long

doi:10.3390/ijms232012624

Cited by 5 publications

(5 citation statements)

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“…Regardless of whether composed of Pluronic F68 or F127, the red fluorescence emitted by encapsulated Nile red was observed in the cell cytoplasm after 2 h of incubation. Moreover, the intranuclear presence of red fluorescence could reveal the delivery of cytoplasmatic release of Nile red and its further diffusion into the nucleus [ 89 ]. While the precise pathways for Nile red delivery within the Pluronic micelles remain elusive, these stabilized structures exhibit a notable ability to encapsulate hydrophobic molecules and facilitate their passage through the cell membrane [ 88 ].…”

Section: Resultsmentioning

confidence: 99%

Gemcitabine-Vitamin E Prodrug-Loaded Micelles for Pancreatic Cancer Therapy

Pereira-Silva,

Miranda-Pastoriza,

Diaz-Gomez

et al. 2024

Pharmaceutics

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Pancreatic cancer (PC) is an aggressive cancer subtype presenting unmet clinical challenges. Conventional chemotherapy, which includes antimetabolite gemcitabine (GEM), is seriously undermined by a short half-life, its lack of targeting ability, and systemic toxicity. GEM incorporation in self-assembled nanosystems is still underexplored due to GEM’s hydrophilicity which hinders efficient encapsulation. We hypothesized that vitamin E succinate–GEM prodrug (VES-GEM conjugate) combines hydrophobicity and multifunctionalities that can facilitate the development of Pluronic®F68 and Pluronic®F127 micelle-based nanocarriers, improving the therapeutic potential of GEM. Pluronic®F68/VES-GEM and Pluronic®F127/VES-GEM micelles covering a wide range of molar ratios were prepared by solvent evaporation applying different purification methods, and characterized regarding size, charge, polydispersity index, morphology, and encapsulation. Moreover, the effect of sonication and ultrasonication and the influence of a co-surfactant were explored together with drug release, stability, blood compatibility, efficacy against tumour cells, and cell uptake. The VES-GEM conjugate-loaded micelles showed acceptable size and high encapsulation efficiency (>95%) following an excipient reduction rationale. Pluronic®F127/VES-GEM micelles evidenced a superior VES-GEM release profile (cumulative release > 50%, pH = 7.4), stability, cell growth inhibition (<50% cell viability for 100 µM VES-GEM), blood compatibility, and extensive cell internalization, and therefore represent a promising approach to leveraging the efficacy and safety of GEM for PC-targeted therapies.

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Section: Resultsmentioning

confidence: 99%

Gemcitabine-Vitamin E Prodrug-Loaded Micelles for Pancreatic Cancer Therapy

Pereira-Silva,

Miranda-Pastoriza,

Diaz-Gomez

et al. 2024

Pharmaceutics

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“… 153 Using nanodrug delivery systems to load chemotherapy drugs has significantly improved drug delivery efficiency and therapeutic effectiveness. 154 Nevertheless, the efficacy of single-drug chemotherapy remains poor for most tumors. Hence, combining chemotherapy with other therapies has become a prominent trend in tumor treatment.…”

Section: Combined Treatment Scheme Based On Ferroptosismentioning

confidence: 99%

Advances in Ferroptosis-Inducing Agents by Targeted Delivery System in Cancer Therapy

Xiang,

Zhou,

Yang

et al. 2024

IJN

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Currently, cancer remains one of the most significant threats to human health. Treatment of most cancers remains challenging, despite the implementation of diverse therapies in clinical practice. In recent years, research on the mechanism of ferroptosis has presented novel perspectives for cancer treatment. Ferroptosis is a regulated cell death process caused by lipid peroxidation of membrane unsaturated fatty acids catalyzed by iron ions. The rapid development of bio-nanotechnology has generated considerable interest in exploiting iron-induced cell death as a new therapeutic target against cancer. This article provides a comprehensive overview of recent advancements at the intersection of iron-induced cell death and bionanotechnology. In this respect, the mechanism of iron-induced cell death and its relation to cancer are summarized. Furthermore, the feasibility of a nano-drug delivery system based on iron-induced cell death for cancer treatment is introduced and analyzed. Secondly, strategies for inducing iron-induced cell death using nanodrug delivery technology are discussed, including promoting Fenton reactions, inhibiting glutathione peroxidase 4, reducing low glutathione levels, and inhibiting system Xc − . Additionally, the article explores the potential of combined treatment strategies involving iron-induced cell death and bionanotechnology. Finally, the application prospects and challenges of iron-induced nanoagents for cancer treatment are discussed.

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“…Additionally, there is a risk of premature drug release in ROS-responsive nanocarriers due to contact with ROS during the delivery process. 31,143 This journal is © The Royal Society of Chemistry 2024 Hence, when developing ROS-responsive oral nanocarrier systems, it is imperative to not only prioritize therapeutic effectiveness but also consider sustained release characteristics and the biocompatibility of the nanocarrier system. Striking a balance between efficacy and safety is paramount in the design process.…”

Section: Ros-responsive Nps Drug Delivery Systemsmentioning

confidence: 99%