Enhanced mucosal penetration and efficient inhibition efficacy against cervical cancer of PEGylated docetaxel nanocrystals by TAT modification

Lv, Feng-mei; Wang, Jun; Chen, Haini; Sui, Li; Feng, Liang; Liu, Zhepeng; Yu, Liu; Wei, Gang; Lu, Weiyue

doi:10.1016/j.jconrel.2021.07.008

Cited by 28 publications

(11 citation statements)

References 36 publications

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“…The exact mechanism of CPP-mediated transport across biological membranes is still unknown. The efficiency and transport mechanism of CPP can be influenced by various factors, including CPP sequence, amphipathicity, charge, cell type, and cargo (Kauffman et al, 2015 ). Based on the energy requirement for the process of internalization, the cellular uptake pathways of CPPs have been generally divided into two categories: the energy-dependent endocytosis and the energy-independent non-endocytic uptake mechanism (Xie et al., 2020 ).…”

Section: Approaches For Enhancing Intracellular Delivery Of Anticance...mentioning

confidence: 99%

Functional ligands for improving anticancer drug therapy: current status and applications to drug delivery systems

et al. 2022

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Conventional chemotherapy lacking target selectivity often leads to severe side effects, limiting the effectiveness of chemotherapy. Therefore, drug delivery systems ensuring both selective drug release and efficient intracellular uptake at the target sites are highly demanded in chemotherapy to improve the quality of life of patients with low toxicity. One of the effective approaches for tumor-selective drug delivery is the adoption of functional ligands that can interact with specific receptors overexpressed in malignant cancer cells. Various functional ligands including folic acid, hyaluronic acid, transferrin, peptides, and antibodies, have been extensively explored to develop tumor-selective drug delivery systems. Furthermore, cell-penetrating peptides or ligands for tight junction opening are also actively pursued to improve the intracellular trafficking of anticancer drugs. Sometimes, multiple ligands with different roles are used in combination to enhance the cellular uptake as well as target selectivity of anticancer drugs. In this review, the current status of various functional ligands applicable to improve the effectiveness of cancer chemotherapy is overviewed with a focus on their roles, characteristics, and preclinical/clinical applications.

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Section: Approaches For Enhancing Intracellular Delivery Of Anticance...mentioning

confidence: 99%

Functional ligands for improving anticancer drug therapy: current status and applications to drug delivery systems

et al. 2022

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“…In fact, Tang et al, attributed Tat-induced synaptic damage to its ability to penetrate cell membranes [ 19 ]. Indeed, a short sequence of Tat is being used as a cell penetrating peptide for delivering drugs in other illnesses like cancer [ 51 ]. It seems that Tat uses different strategies to get inside and out of the cell, which makes it a significant target for prevention of neuronal alterations.…”

Section: Transactivator Of Transcription Tatmentioning

confidence: 99%

Sirtuins Modulation: A Promising Strategy for HIV-Associated Neurocognitive Impairments

Figarola-Centurión

Escoto-Delgadillo

González-Enríquez

et al. 2022

IJMS

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HIV-Associated neurocognitive disorder (HAND) is one of the major concerns since it persists in 40% of this population. Nowadays, HAND neuropathogenesis is considered to be caused by the infected cells that cross the brain–blood barrier and produce viral proteins that can be secreted and internalized into neurons leading to disruption of cellular processes. The evidence points to viral proteins such as Tat as the causal agent for neuronal alteration and thus HAND. The hallmarks in Tat-induced neurodegeneration are endoplasmic reticulum stress and mitochondrial dysfunction. Sirtuins (SIRTs) are NAD+-dependent deacetylases involved in mitochondria biogenesis, unfolded protein response, and intrinsic apoptosis pathway. Tat interaction with these deacetylases causes inhibition of SIRT1 and SIRT3. Studies revealed that SIRTs activation promotes neuroprotection in neurodegenerative diseases such Alzheimer’s and Parkinson’s disease. Therefore, this review focuses on Tat-induced neurotoxicity mechanisms that involve SIRTs as key regulators and their modulation as a therapeutic strategy for tackling HAND and thereby improving the quality of life of people living with HIV.

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“…However, studies have primarily focused on how to enhance targeting efficacy and cell/tissue penetration ability, while attempts to fabricate multi-nanoparticle embedded complexes to enhance the in vivo circulation have been crude. As for nanocrystals, several researchers have attempted to enhance the in vivo performance of docetaxel nanocrystals, for example, after modification with apo-Transferrin human (Tf) [47] or trans-activator of transcription (TAT) peptide [48], the anti-tumor efficacy of unmodified docetaxel micelles was enhanced. However, what needs to be emphasized is that, as a pure drug system, modification of nanocrystals is limited.…”

Section: Pharmacokinetic Behavior Of Doc(nc)@mpeg-plamentioning

confidence: 99%

Nanocrystal-Loaded Micelles for the Enhanced In Vivo Circulation of Docetaxel

et al. 2021

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Prolonging in vivo circulation has proved to be an efficient route for enhancing the therapeutic effect of rapidly metabolized drugs. In this study, we aimed to construct a nanocrystal-loaded micelles delivery system to enhance the blood circulation of docetaxel (DOC). We employed high-pressure homogenization to prepare docetaxel nanocrystals (DOC(Nc)), and then produced docetaxel nanocrystal-loaded micelles (DOC(Nc)@mPEG-PLA) by a thin-film hydration method. The particle sizes of optimized DOC(Nc), docetaxel micelles (DOC@mPEG-PLA), and DOC(Nc)@mPEG-PLA were 168.4, 36.3, and 72.5 nm, respectively. The crystallinity of docetaxel was decreased after transforming it into nanocrystals, and the crystalline state of docetaxel in micelles was amorphous. The constructed DOC(Nc)@mPEG-PLA showed good stability as its particle size showed no significant change in 7 days. Despite their rapid dissolution, docetaxel nanocrystals exhibited higher bioavailability. The micelles prolonged the retention time of docetaxel in the circulation system of rats, and DOC(Nc)@mPEG-PLA exhibited the highest retention time and bioavailability. These results reveal that constructing nanocrystal-loaded micelles may be a promising way to enhance the in vivo circulation and bioavailability of rapidly metabolized drugs such as docetaxel.

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Enhanced mucosal penetration and efficient inhibition efficacy against cervical cancer of PEGylated docetaxel nanocrystals by TAT modification

Cited by 28 publications

References 36 publications

Functional ligands for improving anticancer drug therapy: current status and applications to drug delivery systems

Functional ligands for improving anticancer drug therapy: current status and applications to drug delivery systems

Sirtuins Modulation: A Promising Strategy for HIV-Associated Neurocognitive Impairments

Nanocrystal-Loaded Micelles for the Enhanced In Vivo Circulation of Docetaxel

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