Dataset Information

Decoration of Nanovesicles with pH (Low) Insertion Peptide (pHLIP) for Targeted Delivery.

ABSTRACT: Acidity at surface of cancer cells is a hallmark of tumor microenvironments, which does not depend on tumor perfusion, thus it may serve as a general biomarker for targeting tumor cells. We used the pH (low) insertion peptide (pHLIP) for decoration of liposomes and niosomes. pHLIP senses pH at the surface of cancer cells and inserts into the membrane of targeted cells, and brings nanomaterial to close proximity of cellular membrane. DMPC liposomes and Tween 20 or Span 20 niosomes with and without pHLIP in their coating were fully characterized in order to obtain fundamental understanding on nanocarrier features and facilitate the rational design of acidity sensitive nanovectors. The samples stability over time and in presence of serum was demonstrated. The size, ?-potential, and morphology of nanovectors, as well as their ability to entrap a hydrophilic probe and modulate its release were investigated. pHLIP decorated vesicles could be useful to obtain a prolonged (modified) release of biological active substances for targeting tumors and other acidic diseased tissues.

SUBMITTER: Rinaldi F

PROVIDER: S-EPMC6279677 | biostudies-other | 2018 Dec

REPOSITORIES: biostudies-other

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Decoration of Nanovesicles with pH (Low) Insertion Peptide (pHLIP) for Targeted Delivery.

Rinaldi Federica F Hanieh Patrizia N PN Del Favero Elena E Rondelli Valeria V Brocca Paola P Pereira Mohan C MC Andreev Oleg A OA Reshetnyak Yana K YK Marianecci Carlotta C Carafa Maria M

Nanoscale research letters 20181204 1

Acidity at surface of cancer cells is a hallmark of tumor microenvironments, which does not depend on tumor perfusion, thus it may serve as a general biomarker for targeting tumor cells. We used the pH (low) insertion peptide (pHLIP) for decoration of liposomes and niosomes. pHLIP senses pH at the surface of cancer cells and inserts into the membrane of targeted cells, and brings nanomaterial to close proximity of cellular membrane. DMPC liposomes and Tween 20 or Span 20 niosomes with and withou ...[more]

PMID: 30515583

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Project description:Rationale: miRNA therapeutics have gained attention during the past decade. These oligonucleotide treatments can modulate the expression of miRNAs in vivo and could be used to correct the imbalance of gene expression found in human diseases such as obesity, metabolic syndrome and atherosclerosis. The in vivo efficacy of current anti-miRNAs technologies hindered by physiological and cellular barriers to delivery into targeted cells and the nature of miRNAs that allows one to target an entire pathway that may lead to deleterious off-target effects. For these reasons, novel targeted delivery systems to inhibit miRNAs in specific tissues will be important for developing effective therapeutic strategies for numerous diseases including atherosclerosis. Objective: To explore the application of anti-miR-33 (miR-33-5p) conjugated pH Low-Insertion Peptides (pHLIP) constructs for the specific targeting of macrophages located in vascular lesions in the regression of atherosclerosis. Methods and Results: The anti-miR-33 conjugated pHLIP constructs are preferentially delivered to atherosclerotic plaques macrophages. The inhibition of miR-33 using pHLIP-directed macrophage targeting improves atherosclerosis regression by increasing collagen content and decreased lipid accumulation within vascular lesions. Single cell RNA sequencing analysis revealed higher expression of fibrotic genes (Col2a1, Col3a1, Col1a2, Fn1, etc) and tissue inhibitor of metalloproteinase 3 (Timp3), and downregulation of matrix metallopeptidase 12 (Mmp12) in macrophages from atherosclerotic lesions targeted by pHLIP- anti-miR-33. Conclusions: This study provides proof of principle for the application of pHLIP for treating advanced atherosclerosis via pharmacological inhibition of miR-33 in macrophages that avoids the deleterious effects in other metabolic tissues. This may open new therapeutic opportunities for atherosclerosis-associated cardiovascular diseases via selective delivery of other protective miRNAs.

Dataset Information

Decoration of Nanovesicles with pH (Low) Insertion Peptide (pHLIP) for Targeted Delivery.

Publications

Decoration of Nanovesicles with pH (Low) Insertion Peptide (pHLIP) for Targeted Delivery.

Similar Datasets

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