Cell-penetrating Peptides for Cancer-targeting Therapy and Imaging

Wang, Weiqin; Abbad, Sarra; Zhang, Zhenhai; Wang, Shu; Zhou, Jianping; Lv, Huixia

doi:10.2174/1568009615666150211104524

Cited by 11 publications

(5 citation statements)

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“…The penetration mechanism is not yet fully comprehended, but obviously is associated with the presence of cationic amino acid residues in the peptides. Cell-penetrating peptides have no binding selectivity to cells of a specific molecular profile but significantly facilitate cell entry [270,271].…”

Section: Active Targetingmentioning

confidence: 99%

Targeted Delivery to Tumors: Multidirectional Strategies to Improve Treatment Efficiency

Kutova

Guryev

Соколова

et al. 2019

Cancers

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Malignant tumors are characterized by structural and molecular peculiarities providing a possibility to directionally deliver antitumor drugs with minimal impact on healthy tissues and reduced side effects. Newly formed blood vessels in malignant lesions exhibit chaotic growth, disordered structure, irregular shape and diameter, protrusions, and blind ends, resulting in immature vasculature; the newly formed lymphatic vessels also have aberrant structure. Structural features of the tumor vasculature determine relatively easy penetration of large molecules as well as nanometer-sized particles through a blood–tissue barrier and their accumulation in a tumor tissue. Also, malignant cells have altered molecular profile due to significant changes in tumor cell metabolism at every level from the genome to metabolome. Recently, the tumor interaction with cells of immune system becomes the focus of particular attention, that among others findings resulted in extensive study of cells with preferential tropism to tumor. In this review we summarize the information on the diversity of currently existing approaches to targeted drug delivery to tumor, including (i) passive targeting based on the specific features of tumor vasculature, (ii) active targeting which implies a specific binding of the antitumor agent with its molecular target, and (iii) cell-mediated tumor targeting.

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Section: Active Targetingmentioning

confidence: 99%

Targeted Delivery to Tumors: Multidirectional Strategies to Improve Treatment Efficiency

Kutova

Guryev

Соколова

et al. 2019

Cancers

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“…Active targeting by the addition of a binding moiety (antibody or tumor-homing peptide) ensures specific attachment of CPP-nucleic acid complexes to target molecules overexpressed on the cancer cell surface. 3,[12][13][14] However, this strategy has problems: 1) adding a targeting moiety will not eliminate the uptake ability of CPP cargos by normal cells, which often causes undesired side effects; 3 2) sometimes the delivery efficacy is lost or the internalization mode is altered when CPP cargos are coupled to the targeting moiety. 13 Passive targeting of CPP-based nucleic acid complexes is frequently pursued through changing properties (eg, enhanced permeability and retention effect) caused by a reaction with endogenous microenvironment factors (eg, pH, enzyme) at tumor sites.…”

Section: Introductionmentioning

confidence: 99%

“…Although attaining encouraging results, these passive targeting practices are still limited by the spatial distribution of the tumor microenvironment. 8,11,12,15,16 Therefore, novel approaches to enhance the targeting efficiency of CPP-delivered nucleic acid drugs specifically to tumors are urgent.…”

Section: Introductionmentioning

confidence: 99%

Macropinocytosis activated by oncogenic Dbl enables specific targeted delivery of Tat/pDNA nano-complexes into ovarian cancer cells

Niu¹,

Gao²,

Qi³

et al. 2018

IJN

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BackgroundSuccessful implementation of gene therapy heavily relies on efficiently delivering genetic materials and specific targeting into cells. Oncogene-driven endocytosis stimulates nutrient uptake and also develops an endocytosis-mediated defense against therapeutic agents. Cell-penetrating peptides, typically HIV-Tat, are well known for efficient delivery of nucleic acid drugs but lack targeting specificity. Various passive targeting strategies were pursued to enhance the tumor targeting efficiency; however, they are still limited by complicated cellular endocytosis routes and the heterogeneity of cancer types.MethodsTat/pDNA complexes were noncovalently compacted and their physiochemical properties were determined. The siRNA pool and pLV-RNAi-GFP lentivirus were used to knock down dbl oncogene (originally isolated from diffuse B-cell lymphoma) expression, and its overexpression was performed by plasmid transient transfection. The cellular uptake of fluorescent ligands was quantified by confocal imaging and flow cytometry analysis. The transgene efficiency was determined by the Luciferase expression assay. Rho GTPase activation was checked by the GST-Rho GTPase-binding domain pull-down assay.ResultspGL3 plasmid DNA was noncovalently compacted with the Tat peptide into nano-size complexes at high N/P ratios. Macropinocytosis, a clathrin- and caveolin-independent endocytosis process, was shown to contribute to the uptake of middle-sized (∼600 nm) Tat/pGL3 complexes. Cell-type-specific variation in macropinocytosis was essentially controlled by the action of the Dbl oncogene. Onco-Dbl presentation constantly induced a high level of macropinocytosis activity in ovarian cancer cells. Onco-Dbl overexpression hyperstimulated macropinocytosis enhancement in cells mainly through actin cytoskeleton reorganization mediated by the PH domain and Rac1 activation. The Dbl-driven Rho GTPase signaling collectively determined the cell-type-specific macropinocytosis phenotype.ConclusionSuch an aspect can be exploited to selectively confer targeted delivery of Tat/pDNA nano-complexes into ovarian cancer cells. Our work provides a novel alternative for targeted delivery of cell-penetrating peptide-based nucleic acid drugs into certain tumor types if specific endocytosis pathways are used.

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“…The hWAPL protein is highly expressed in cervical cancer patients, and HPV E6 and E7 oncoproteins induce hWAPL expression ( 25 ). Moreover, HPV E6 is associated with cervical carcinogenesis, and as such, is a therapeutic target for cervical cancer ( 26 ). Nevertheless, little is known about the function of hWAPL in cervical cancer.…”

Section: Discussionmentioning

confidence: 99%

TAT‑mediated si‑hWAPL inhibits the invasion and metastasis of cervical cancer stem cells

Gong

Zhou

et al. 2017

Exp Ther Med

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Human wings apart-like (hWAPL) is reported to have an association with cervical cancer. In the present study, the role of hWAPL in cervical cancer stem cells (CCSCs) was evaluated. Cervical tumorspheres were generated from cervical cancer tissues cultured in stem cell medium, and the expression of hWAPL by the tumorspheres was detected using immunohistochemistry. hWAPL expression levels in the tumorspheres were then upregulated using hWAPL adenoviral vectors or downregulated via the TAT-mediated knockdown of hWAPL and the effects on the tumorspheres were evaluated using colony formation, cell invasion and western blotting assays. The results demonstrated that the expression of hWAPL and human papillomavirus (HPV) was associated with the pluripotency of CCSCs, with hWAPL expression decreasing following the differentiation of cervical tumorspheres. Knockdown of hWAPL expression decreased HPV E6 expression and inhibited tumor invasion and colony formation. TAT-mediated knockdown of hWAPL with short interfering RNA significantly reduced tumor growth in nude mice. These results suggest that hWAPL is a marker of CCSC proliferation and is potentially a therapeutic target for cervical carcinoma through the downregulation of HPV E6.

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Cell-penetrating Peptides for Cancer-targeting Therapy and Imaging

Cited by 11 publications

References 0 publications

Targeted Delivery to Tumors: Multidirectional Strategies to Improve Treatment Efficiency

Targeted Delivery to Tumors: Multidirectional Strategies to Improve Treatment Efficiency

Macropinocytosis activated by oncogenic Dbl enables specific targeted delivery of Tat/pDNA nano-complexes into ovarian cancer cells

TAT‑mediated si‑hWAPL inhibits the invasion and metastasis of cervical cancer stem cells

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