&lt;p&gt;Distinct Proteins in Protein Corona of Nanoparticles Represent a Promising Venue for Endogenous Targeting – Part I: In vitro Release and Intracellular Uptake Perspective&lt;/p&gt;

Sebak, Aya; Gomaa, Iman; ElMeshad, Aliaa Nabil; Farag, Mahmoud Hussien; Breitinger, Hans‐Georg; Abdel‐Kader, Mahmoud H.

doi:10.2147/ijn.s273713

Cited by 20 publications

(19 citation statements)

References 66 publications

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“… 63 In addition, the mechanism of the intracellular uptake has proven to contribute to a great extent to both uptake and the elimination of the NPs. In part I of this study, 27 the evaluation of the endocytic mechanism of the NPs’ uptake has been performed. The results suggest that the NPs are internalized via an energy-dependent pathway.…”

Section: Discussionmentioning

confidence: 99%

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<p>Distinct Proteins in Protein Corona of Nanoparticles Represent a Promising Venue for Endogenous Targeting – Part II: In vitro and in vivo Kinetics Study</p>

Sebak

Gomaa

ElMeshad

et al. 2020

IJN

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Introduction: Nanoparticles (NPs), upon introduction to the biological systems, become wrapped by serum and cellular proteins constituting the protein corona (PC). This PC contributes largely to the NPs' interaction with the biological systems and their subsequent functions. On the one hand, PC can decrease the efficiency of targeting by directing the NPs to the reticuloendothelial system (RES) or by masking the active targeting moieties and decreasing their ability to bind to their target receptors. On the other hand, some components of PC have offered hopes for achieving endogenous targeting. Methods: In this study, we aimed at the investigation of the role of the PC in determining the behavior of cRGDyk peptide-unconjugated and-conjugated NPs (uNPs and cNPs) exhibiting different physicochemical properties and their interaction with melanoma on in vitro and in vivo levels. Mathematical modeling has been utilized to understand the kinetics of the interaction of NPs with the tumor cells and different organs, respectively. Results: Endocytosis and exocytosis were reported to occur simultaneously for the utilized NPs. The balance was largely dependent on the NPs' physicochemical properties and the role of the PC. In addition, distinct proteins present in the PC (illustrated in the results of the PC analysis in part I) have also determined the patterns of the NPs' distribution in different organs and tissues of the vascular system, the RES system and the target tumot tissue. Vitronectin (VN) was found to mediate higher accumulation in integrin receptor-expressing melanoma cells, while complement 3 protein (C3) and clusterin (CLU), as an opsonin and dysopsonin, respectively, regulated the balance between the RES uptake and blood circulation. Discussion: PC, if properly modulated by tuning NPs' physicochemical properties, can serve as a potential venue for optimum utilization of NPs in cancer therapy.

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Section: Discussionmentioning

confidence: 99%

“…In the first part of this study, 27 NPs possessing different physicochemical properties were synthesized. Polylactic co-glycolic acid (PLGA) NPs (NP1 and NP2) and lipid-polymer hybrid NPs (NP3 and NP4) were synthesized to constitute the uNPs.…”

Section: Introductionmentioning

confidence: 99%

<p>Distinct Proteins in Protein Corona of Nanoparticles Represent a Promising Venue for Endogenous Targeting – Part II: In vitro and in vivo Kinetics Study</p>

Sebak

Gomaa

ElMeshad

et al. 2020

IJN

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“…For determination of the intracellular concentration of TFs, a modified protocol by Sebak et al 68 was followed. A noncytotoxic concentration of 250 μg/mL fluorescein-loaded TFs was incubated with the activated and nonactivated B16F10 melanoma cells under 37°C and 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

“…Similarly, 20 μM nystatin and 50 μM amiloride were utilized as inhibitors of caveolin-dependent endocytosis and micropinocytosis, respectively. [68][69][70][71]…”

Section: Intracellular Uptake Of Fluorescein-loaded Tfs and Mechanism Of Endocytosismentioning

confidence: 99%

Green Synthesized Honokiol Transfersomes Relieve the Immunosuppressive and Stem-Like Cell Characteristics of the Aggressive B16F10 Melanoma

Ezzeldeen¹,

Swidan²,

ElMeshad³

et al. 2021

IJN

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Background: Honokiol (HK) is a natural bioactive compound with proven antineoplastic properties against melanoma. However, it shows very low bioavailability when administered orally. Alternatively, topical administration may offer a promising route. The objective of the current study was to fabricate HK transfersomes (HKTs) for topical treatment of melanoma. As an ultradeformable carrier system, transfersomes can overcome the physiological barriers to topical treatment of melanoma: the stratum corneum and the anomalous tumor microenvironment. Moreover, the immunomodulatory and stemness-regulation roles of HKTs were the main interest of this study. Methods: TFs were prepared using the modified scalable heating method. A three-factor, three-level Box-Behnken design was utilized for the optimization of the process and formulation variables. Intracellular uptake and cytotoxicity of HKTs were evaluated in nonactivated and stromal cell-activated B16F10 melanoma cells to investigate the influence of the complex tumor microenvironment on the efficacy of HK. Finally, ELISA and Western blot were performed to evaluate the expression levels of TGF-β and clusters of differentiation (CD47 and CD133, respectively). Results: The optimized formula exhibited a mean size of 190 nm, highly negative surface charge, high entrapment efficiency, and sustained release profile. HKTs showed potential to alleviate the immunosuppressive characteristics of B16F10 melanoma in vitro via downregulation of TGF-β signaling. In addition, HKTs reduced expression of the "do not eat me" signal -CD47. Moreover, HKTs possessed additional interesting potential to reduce the expression of the stem-like cell marker CD133. These outcomes were boosted upon combination with metformin, an antihyperglycemic drug recently reported to possess different functions in cancer, while combination with collagenase, an extracellular matrix-depleting enzyme, produced detrimental effects. Conclusion: HKTs represent a promising scalable formulation for treatment of the aggressive B16F10 melanoma, which is jam-packed with immunosuppressive and stem-like cell markers.

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“…When injected into a biological system, nanomaterials are surrounded by serum and cellular proteins, structures formed by these substances are termed protein corona (PC) [ 261 ]. Searching for technology that helps manufacture vast nanomaterials with combined required properties is one important goal in anticancer nanomaterial clinical translation.…”

Section: Cancer Treatment and Nanomaterials Designmentioning

confidence: 99%

Nanomaterials for cancer therapy: current progress and perspectives

et al. 2021

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Cancer is a disease with complex pathological process. Current chemotherapy faces problems such as lack of specificity, cytotoxicity, induction of multi-drug resistance and stem-like cells growth. Nanomaterials are materials in the nanorange 1–100 nm which possess unique optical, magnetic, and electrical properties. Nanomaterials used in cancer therapy can be classified into several main categories. Targeting cancer cells, tumor microenvironment, and immune system, these nanomaterials have been modified for a wide range of cancer therapies to overcome toxicity and lack of specificity, enhance drug capacity as well as bioavailability. Although the number of studies has been increasing, the number of approved nano-drugs has not increased much over the years. To better improve clinical translation, further research is needed for targeted drug delivery by nano-carriers to reduce toxicity, enhance permeability and retention effects, and minimize the shielding effect of protein corona. This review summarizes novel nanomaterials fabricated in research and clinical use, discusses current limitations and obstacles that hinder the translation from research to clinical use, and provides suggestions for more efficient adoption of nanomaterials in cancer therapy.

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<p>Distinct Proteins in Protein Corona of Nanoparticles Represent a Promising Venue for Endogenous Targeting – Part I: In vitro Release and Intracellular Uptake Perspective</p>

Cited by 20 publications

References 66 publications

<p>Distinct Proteins in Protein Corona of Nanoparticles Represent a Promising Venue for Endogenous Targeting – Part II: In vitro and in vivo Kinetics Study</p>

<p>Distinct Proteins in Protein Corona of Nanoparticles Represent a Promising Venue for Endogenous Targeting – Part II: In vitro and in vivo Kinetics Study</p>

Green Synthesized Honokiol Transfersomes Relieve the Immunosuppressive and Stem-Like Cell Characteristics of the Aggressive B16F10 Melanoma

Nanomaterials for cancer therapy: current progress and perspectives

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