Metformin-encapsulating immunoliposomes conjugated with anti-TROP 2 antibody fragments for the active targeting of triple-negative breast cancer.

Trophoblast cell-surface antigen 2 (TROP 2) has re-emerged as a promising biomarker in triple-negative breast cancer (TNBC), with high overexpression in many TNBC cases. However, despite its potential and approval as an antibody-drug-conjugate for TNBC treatment, TROP 2-targeted delivery systems are currently underexplored. Therefore, this study was aimed at exploiting the potential of TROP 2 targeting by encapsulating metformin (Met), an antidiabetic drug associated with tumor growth inhibitory properties, inside liposomes decorated with TROP 2-targeting single-chain variable fragments (scFvs).

Design, optimization, characterization, and evaluation of metformin-loaded liposomes for triple negative breast cancer treatment.

Recently, metformin (Met) has shown to have antineoplastic properties in cancer treatment by improving hypoxic tumor conditions, and causing reduction in the synthesis of biomolecules, which are vital for cancer growth. However, as an orally administered drug, Met has low bioavailability and rapid renal clearance. Thus, the goal of this study was to vectorize Met inside liposomes in the context of triple negative breast cancer (TNBC), which currently lacks treatment options when compared to other types of breast cancer.

Radiolabeling, Quality Control and In Vivo Imaging of Multimodal Targeted Nanomedicines.

Following our previous study on the development of EGFR-targeted nanomedicine (NM-scFv) for the active delivery of siRNA in EGFR-positive cancers, this study focuses on the development and the quality control of a radiolabeling method to track it in in vivo conditions with nuclear imaging. Our NM-scFv is based on the electrostatic complexation of targeted nanovector (NV-scFv), siRNA and two cationic polymers. NV-scFv comprises an inorganic core, a fluorescent dye, a polymer layer and anti-EGFR ligands.

Formation of miRNA Nanoprobes-Conjugation Approaches Leading to the Functionalization.

Recently, microRNAs (miRNA) captured the interest as novel diagnostic and prognostic biomarkers, with their potential for early indication of numerous pathologies. Since miRNA is a short, non-coding RNA sequence, the sensitivity and selectivity of their detection remain a cornerstone of scientific research. As such, methods based on nanomaterials have emerged in hopes of developing fast and facile approaches.

Combination of Nanovectorized siRNA Directed against Survivin with Doxorubicin for Efficient Anti-Cancer Activity in HER2+ Breast Cancer Cells.

According to Globocan 2020, breast cancer is considered one of the most common cancers affecting women and is one of the leading causes of death in over 100 countries. The available classical treatment options do not always give satisfactory outcomes, and some patients develop resistance to these treatments. This study aims to investigate the combination of nanovectorized siRNA directed against anti-apoptotic protein Survivin (siSurvivin) by targeted stealth magnetic siRNA nanovectors (TS-MSN), designed in our lab, with Doxorubicin (DOX), as an option for HER2+ breast cancer treatment.

synergistic activity of cisplatin and EGFR-targeted nanomedicine of anti-Bcl-xL siRNA in a non-small lung cancer cell line model.

Apoptosis is an important process that directly affects the response of cancer cells to anticancer drugs. Among different factors involved in this process, the BcL-xL protein plays a critical role in inhibiting apoptosis induced by chemotherapy agents. Henceforth, its downregulation may have a synergistic activity that lowers the necessary dose of anticancer agents.

WITHDRAWN: In vitro synergistic activity of cisplatin and EGFR-targeted nanomedicine of anti-Bcl-xL siRNA in a non-small lung cancer cell line model.

This article was withdrawn from International Journal of Pharmaceutics in order to be published in International Journal of Pharmaceutics: X. The Publisher apologizes for any inconvenience this may cause.

Design and Validation of Nanofibers Made of Self-Assembled Peptides to Become Multifunctional Stimuli-Sensitive Nanovectors of Anticancer Drug Doxorubicin.

Self-assembled peptides possess remarkable potential as targeted drug delivery systems and key applications dwell anti-cancer therapy. Peptides can self-assemble into nanostructures of diverse sizes and shapes in response to changing environmental conditions (pH, temperature, ionic strength). Herein, we investigated the development of self-assembled peptide-based nanofibers (NFs) with the inclusion of a cell-penetrating peptide (namely gH625) and a matrix metalloproteinase-9 (MMP-9) responsive sequence, which proved to enhance respectively the penetration and tumor-triggered cleavage to release Doxorubicin in Triple Negative Breast Cancer cells where MMP-9 levels are elevated.

Peptides to Overcome the Limitations of Current Anticancer and Antimicrobial Nanotherapies.

Biomedical research devotes a huge effort to the development of efficient non-viral nanovectors (NV) to improve the effectiveness of standard therapies. NVs should be stable, sustainable and biocompatible and enable controlled and targeted delivery of drugs. With the aim to foster the advancements of such devices, this review reports some recent results applicable to treat two types of pathologies, cancer and microbial infections, aiming to provide guidance in the overall design of personalized nanomedicines and highlight the key role played by peptides in this field.

Two-step formulation of magnetic nanoprobes for microRNA capture.

MicroRNAs (miRs) belong to a family of short non-coding endogenous RNAs. Their over-expression correlates with various pathologies: for instance, miRNA-155 (miR-155) is over-expressed upon the development of breast cancers. However, the detection of miRs as disease biomarkers suffers from insufficient sensitivity.

Active targeting strategy in nanomedicines using anti-EGFR ligands - A promising approach for cancer therapy and diagnosis.

As active targeting using nanomedicines establishes itself as a strategy of choice in cancer therapy, several target receptors or ligands overexpressed in cancer cells have been identified and exploited. Among them, the epidermal growth factor receptor (EGFR) has emerged as one of the most promising oncomarkers for active targeting nanomedicines due to its overexpression and its active involvement in a wide range of cancer types. Henceforth, many novel EGFR-targeted nanomedicines for cancer therapy have been developed, giving encouraging results both in vitro and in vivo.

Nanomedicines functionalized with anti-EGFR ligands for active targeting in cancer therapy: Biological strategy, design and quality control.

Recently, active targeting using nanocarriers with biological ligands has emerged as a novel strategy for improving the delivery of therapeutic and/or imaging agents to tumor cells. The presence of active targeting moieties on the surface of nanomedicines has been shown to play an important role in enhancing their accumulation in tumoral cells and tissues versus healthy ones. This property not only helps to increase the therapeutic index but also to minimize possible side effects of the designed nanocarriers.

Targeted nanomedicine with anti-EGFR scFv for siRNA delivery into triple negative breast cancer cells.

A targeted nanomedicine with humanized anti-EGFR scFv (NM-scFv) was developed for siRNA delivery into triple negative breast cancer (TNBC) cells. NM-scFv consisted of i) targeted nanovector (NV-scFv): nano-cargo with targeting properties; ii) siRNA: pharmacological agent and iii) cationic polymers (chitosan, poly-L-arginine): for siRNA complexation and endosomal escape. NV-scFv was based on superparamagnetic nanoparticle (SPION) labeled with Dylight™680, a PEG layer and a humanized anti-EGFR scFv.

One-step synthesis of gold nanoflowers of tunable size and absorption wavelength in the red & deep red range for SERS spectroscopy.

We describe a novel protocol for a one-step, seed-less, organic solvent- and surfactant-free synthesis of optically dense aqueous colloids of gold nanoflowers (AuNF), with tunable absorption wavelength between 620 and 800 nm. We demonstrate that simple variation of the ratio of two reagents allows the plasmonic band position to be tuned to any desired wavelength ± 5 nm, namely to those of the laser sources commonly used for SERS spectroscopy. The AuNF size distribution was sufficiently narrow, comparable to that known with seed-mediated synthesis.

Magnetic nanocarriers for the specific delivery of siRNA: Contribution of breast cancer cells active targeting for down-regulation efficiency.

The association between superparamagnetic iron oxide nanoparticles (SPION), carrying small interfering RNA (siRNA) as therapeutic agents and humanized anti- human epidermal growth factor receptor-2 (HER2) single-chain antibody fragments (scFv) for the active delivery into HER2-overexpressing cells appears as an interesting approach for patients with HER2-overexpressing advanced breast cancer. The obtained Targeted Stealth Magnetic siRNA Nanovectors (TS-MSN) are formulated by combining: (i) the synthesis protocol of Targeted Stealth Fluorescent Particles (T-SFP) which form the core of TS-MSN and (ii) the formulation protocol allowing the loading of T-SFP with polyplexes (siRNA and cationic polymers). TS-MSN have suitable physico-chemical characteristics for intravenous administration and protect siRNA against enzymatic degradation up to 24 h.

gH625 Cell-Penetrating Peptide Promotes the Endosomal Escape of Nanovectorized siRNA in a Triple-Negative Breast Cancer Cell Line.

The use of small interfering RNA (siRNA) to regulate oncogenes appears as a promising strategy in the context of cancer therapy, especially if they are vectorized by a smart delivery system. In this study, we investigated the cellular trafficking of a siRNA nanovector (called CS-MSN) functionalized with the cell-penetrating peptide gH625 in a triple-negative breast cancer model. With complementary techniques, we showed that siRNA nanovectors were internalized by both clathrin- and caveolae-mediated endocytosis.

Formulation and in vitro evaluation of a siRNA delivery nanosystem decorated with gH625 peptide for triple negative breast cancer theranosis.

The development of an efficient small interfering RNA (siRNA) delivery system has held scientists interest since the discovery of the RNA interference mechanism (RNAi). This strategy gives hope for the treatment of many severe diseases. Herein, we developed hybrid nanovectors able to deliver siRNA to triple negative breast cancer cells.

Impact of Site-Specific Conjugation of ScFv to Multifunctional Nanomedicines Using Second Generation Maleimide.

Biocompatible multifunctional nanomedicines (NMs) are known to be an attractive platform for targeted anticancer theranosis. However, these nanomedicines are of interest only if they efficiently target diseased cells and accumulate in tumors. Here we report the synthesis of a new generation of immunotargeted nanomedicines composed of a superparamagnetic iron oxide nanoparticle (SPION) core, polyethylene glycol coating and the anti-HER2 single chain fragment variable (scFv) of Trastuzumab antibody.

Targeting HER2-breast tumors with scFv-decorated bimodal nanoprobes.

Background: Recent advances in nanomedicine have shown the great interest of active targeting associated to nanoparticles. Single chain variable fragments (scFv) of disease-specific antibodies are very promising targeting entities because they are small, not immunogenic and able to bind their specific antigens. The present paper is devoted to biological properties in vitro and in vivo of fluorescent and pegylated iron oxide nanoparticles (SPIONs-Cy-PEG-scFv) functionalized with scFv targeting Human Epithelial growth Receptor 2 (HER2).

siRNA delivery system based on magnetic nanovectors: Characterization and stability evaluation.

Gene therapy and particularly small interfering RNA (siRNA) is a promising therapeutic method for treatment of various human diseases, especially cancer. However the lack of an ideal delivery system limits its clinical applications. Effective anticancer drug development represents the key for translation of research advances into medicines.

Stealth magnetic nanocarriers of siRNA as platform for breast cancer theranostics.

The endogenous mechanism of RNA interference is more and more used in research to obtain specific down-regulation of gene expression in diseases such as breast cancer. Currently, despite the new fields of study open up by RNA interference, the rapid degradation of siRNA by nucleases and their negative charges prevent them from crossing cell membranes. To overcome these limitations, superparamagnetic iron oxide nanoparticles (SPIONs) represent a promising alternative for nucleic acid delivery.

Synthesis and in vitro evaluation of fluorescent and magnetic nanoparticles functionalized with a cell penetrating peptide for cancer theranosis.

We synthesized rationally designed multifunctional nanoparticles (NPs) composed of a superparamagnetic iron oxide nanoparticle (SPION) core, cyanine fluorescent dye emitting in far red, polyethylene glycol (PEG) coating, and the membranotropic peptide gH625, from the cell-penetrating peptides (CPP) family. The peptide sequence was enriched with an additional cysteine so it can be involved as a reactive moiety in a certain orientation- and sequence-specific coupling of the CPP to the PEG shell of the NPs. Our data indicate that the presence of approximately 23 peptide molecules per SPION coated with approximately 137 PEG chains minimally changes the overall NP characteristics.

Folic acid-capped PEGylated magnetic nanoparticles enter cancer cells mostly via clathrin-dependent endocytosis.

Background: This work is focused on mechanisms of uptake in cancer cells of rationally designed, covalently assembled nanoparticles, made of superparamagnetic iron oxide nanoparticles (SPIONs), fluorophores (doxorubicin or Nile Blue), polyethylene glycol (PEG) and folic acid (FA), referred hereinafter as SFP-FA.

Methods: SFP-FA were characterized by DLS, zetametry and fluorescence spectroscopy. The SFP-FA uptake in cancer cells was monitored using fluorescence-based methods like fluorescence-assisted cell sorting, CLSM with single-photon and two-photon excitation.

Design strategies of hybrid metallic nanoparticles for theragnostic applications.

Metallic nanoparticles (MNPs) such as iron oxide and gold nanoparticles are interesting platforms to build theragnostic nanocarriers which combine both therapeutic and diagnostic functions within a single nanostructure. Nevertheless, their surface must be functionalized to be suitable for in vivo applications. Surface functionalization also provides binding sites for targeting ligands, and for drug loading.

Colloidal stability and thermo-responsive properties of iron oxide nanoparticles coated with polymers: advantages of Pluronic® F68-PEG mixture.

Superparamagnetic iron oxide nanoparticles (SPIONs) are recognized to be an attractive platform for developing novel drug delivery approaches and thus several types of functionalized magnetic nanocarriers based on SPIONs have been synthesized and studied. The coating of the metal oxide surface was achieved in a one-pot synthesis with biocompatible polyethylene glycol (PEG) and thermo-responsive modified Pluronic® F68. The resulting thermo-responsive magnetic nanocarriers can incorporate water insoluble drugs into their hydrophobic compartment and later release them in a temperature dependent manner.