Phosphatidylserine targeting peptide-functionalized pH sensitive mixed micelles for enhanced anti-tumor drug delivery

Guan, Siyu; Zhang, Qianqian; Bao, Jianwei; Duan, Tijie; Hu, Rongfeng; Czech, Tori; Tang, Jihui

doi:10.1016/j.ejpb.2019.12.012

Cited by 19 publications

(11 citation statements)

References 45 publications

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“…Similarly, more than 85% reduction in the uptake of micelles was recorded at 4 °C (data not shown). While binding of free PBA would have rendered the majority of diol sites inaccessible to functionalized micelles in the first case, uptake reduction in the second case strongly suggests that internalization occurred through an energy-dependent, receptor-mediated mechanism [ 37 ]. Our results are in agreement with the observations of Tang and coworkers [ 38 ] on PBA-functionalized gelatin nanoparticles.…”

Section: Resultsmentioning

confidence: 99%

Synthesis, Colloidal Characterization and Targetability of Phenylboronic Acid Functionalized α-Tocopheryl Polyethylene Glycol Succinate in Cancer Cells

et al. 2020

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This study reports targetable micelles developed after covalent functionalization of α-tocopheryl polyethylene glycol succinate (TPGS) with amino phenylboronic acid (APBA). Nuclear magnetic resonance (NMR) and infrared (IR) spectroscopic results showed successful attachment of APBA to the hydrophilic segment of TPGS. Dynamic light scattering and small-angle neutron scattering studies revealed that the conjugate self-assembled in water to produce spherical core-shell micelles (14–20 nm) which remained stable against temperature (ca. 25–45 °C) and pH changes. The micelles could solubilize a high payload of paclitaxel (PLX) without exhibiting changes in the average size. However, at the saturation solubility, drug molecules migrated from the core to the shell region and engaged with APBA groups via π–π stacking interaction. Confocal microscopy and cell sorting analyses verified the effective translocation ability of TPGS-APBA micelles in sialic acid (SA) expressing MDA-MB-453 cells. At equivalent PLX dose, TPGS-APBA micelles showed about a twofold improvement in apoptotic death among the cells exposed for 2 h. Our findings indicate that the attachment of APBA can be a potential strategy for improving the intra-cellular localization of carriers among cancer cells expressing SA residues.

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Section: Resultsmentioning

confidence: 99%

Synthesis, Colloidal Characterization and Targetability of Phenylboronic Acid Functionalized α-Tocopheryl Polyethylene Glycol Succinate in Cancer Cells

et al. 2020

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“…These pH sensitive micelles represent an acid triggered drug release system that is suitable for the acidic tumor environment. An in vivo study showed that the conjugated agents had improved cytotoxicity and uptake by tumor cells, as well as accumulation at tumor sites 157 .…”

Section: Ps Binding Molecules and Cancer Therapymentioning

confidence: 99%

Targeting phosphatidylserine for Cancer therapy: prospects and challenges

Chang

Xiao

et al. 2020

Theranostics

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Cancer is a leading cause of mortality and morbidity worldwide. Despite major improvements in current therapeutic methods, ideal therapeutic strategies for improved tumor elimination are still lacking. Recently, immunotherapy has attracted much attention, and many immune-active agents have been approved for clinical use alone or in combination with other cancer drugs. However, some patients have a poor response to these agents. New agents and strategies are needed to overcome such deficiencies. Phosphatidylserine (PS) is an essential component of bilayer cell membranes and is normally present in the inner leaflet. In the physiological state, PS exposure on the external leaflet not only acts as an engulfment signal for phagocytosis in apoptotic cells but also participates in blood coagulation, myoblast fusion and immune regulation in nonapoptotic cells. In the tumor microenvironment, PS exposure is significantly increased on the surface of tumor cells or tumor cell-derived microvesicles, which have innate immunosuppressive properties and facilitate tumor growth and metastasis. To date, agents targeting PS have been developed, some of which are under investigation in clinical trials as combination drugs for various cancers. However, controversial results are emerging in laboratory research as well as in clinical trials, and the efficiency of PS-targeting agents remains uncertain. In this review, we summarize recent progress in our understanding of the physiological and pathological roles of PS, with a focus on immune suppressive features. In addition, we discuss current drug developments that are based on PS-targeting strategies in both experimental and clinical studies. We hope to provide a future research direction for the development of new agents for cancer therapy.

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“…In recent years, drug delivery systems (DDSs) based on nanocarriers have been widely developed, and antitumor drug carriers (such as liposomes (Wang et al, 2020 ), micelles (Guan et al, 2020 ), polymer nanogels (Maiti et al, 2018 ), magnetic nanoparticles (NPs) (Avval et al, 2020 ), and nanocapsules (de Cristo Soares Alves et al, 2020 )) are usually produced on the nanoscale to increase their permeability and retention in tumor tissues. However, these carriers are identified as ‘nonself’ and are still quickly cleared by the immune system with a short half-life.…”

Section: Introductionmentioning

confidence: 99%

Cell-derived biomimetic nanocarriers for targeted cancer therapy: cell membranes and extracellular vesicles

Zhao

et al. 2021

Drug Delivery

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Nanotechnology provides synthetic carriers for cancer drug delivery that protect cargos from degradation, control drug release and increase local accumulation at tumors. However, these non-natural vehicles display poor tumor targeting and potential toxicity and are eliminated by the immune system. Recently, biomimetic nanocarriers have been widely developed based on the concept of 'mimicking nature.' Among them, cell-derived biomimetic vehicles have become the focus of bionics research because of their multiple natural functions, such as low immunogenicity, long circulation time and targeting ability. Cell membrane-coated carriers and extracellular vesicles are two widely used cell-based biomimetic materials. Here, this review summarizes the latest progress in the application of these two biomimetic carriers in targeted cancer therapy. Their properties and performance are compared, and their future challenges and development prospects are discussed.

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Phosphatidylserine targeting peptide-functionalized pH sensitive mixed micelles for enhanced anti-tumor drug delivery

Cited by 19 publications

References 45 publications

Synthesis, Colloidal Characterization and Targetability of Phenylboronic Acid Functionalized α-Tocopheryl Polyethylene Glycol Succinate in Cancer Cells

Synthesis, Colloidal Characterization and Targetability of Phenylboronic Acid Functionalized α-Tocopheryl Polyethylene Glycol Succinate in Cancer Cells

Targeting phosphatidylserine for Cancer therapy: prospects and challenges

Cell-derived biomimetic nanocarriers for targeted cancer therapy: cell membranes and extracellular vesicles

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