Fluorescence lifetime nanothermometer based on the equilibrium formation of anthracene AIE-excimers in living cells.

The effective measurement of temperature in living systems at the nano and microscopic scales continues to be a challenge to this day. Here, we study the use of 2-(anthracen-2-yl)-1,3-diisopropylguanidine, 1, as a nanothermometer based on fluorescence lifetime measurements and its bioimaging applications. In aqueous solution, 1 is shown in aggregated form and the equilibrium between the two main aggregate types (T-shaped and π-π) is highly sensitive to the temperature. The heating of the medium shifts the equilibrium toward the formation of highly emissive T-shaped aggregates. This species shows a high fluorescence emission and a long lifetime in comparison with the π-π aggregates and the freé monomer. A linear relationship between the fluorescence lifetime and the temperature both in aqueous solution and in a synthetic intracellular buffer was found. Fluorescence lifetime imaging microscopy (FLIM) also showed a linear relationship between lifetime and temperature with an excellent sensitivity in MCF7 breast cancer cells, which opens the door for its potential use as FLIM nanothermometer in the biomedical field.

Evaluation of heteroscorpionate ligands as scaffolds for the generation of Ruthenium(II) metallodrugs in breast cancer therapy.

The modular synthesis of the heteroscorpionate core is explored as a tool for the rapid development of ruthenium-based therapeutic agents. Starting with a series of structurally diverse alcohol-NN ligands, a family of heteroscorpionate-based ruthenium derivatives was synthesized, characterized, and evaluated as an alternative to platinum therapy for breast cancer therapy. In vitro, the antitumoral activity of the novel derivatives was assessed in a series of breast cancer cell lines using UNICAM-1 and cisplatin as metallodrug control. Through this approach, a bimetallic heteroscorpionate-based metallodrug (RUSCO-2) was identified as the lead compound of the series with an IC50 value range as low as 3-5 µM. Notably, RUSCO-2 was found to be highly cytotoxic in TNBC cell lines, suggesting a mode of action independent of the receptor status of the cells. As a proof of concept and taking advantage of the luminescent properties of one of the complexes obtained, uptake was monitored in human breast cancer MCF7 cell lines by fluorescence lifetime imaging microscopy (FLIM) to reveal that the compound is evenly distributed in the cytoplasm and that the incorporation of the heteroscorpionate ligand protects it from aqueous processes, conversion in another entity, or the loss of the chloride group. Finally, ROS studies were conducted, lipophilicity was estimated, the chloride/water exchange was studied, and stability studies in simulated biological media were carried out to propose structure-activity relationships.

Formation of Highly Emissive Anthracene Excimers for Aggregation-Induced Emission/Self-Assembly Directed (Bio)imaging.

AIEgens have emerged as a promising alternative to molecular rotors in bioimaging applications. However, transferring the concept of aggregation-induced emission (AIE) from solution to living systems remains a challenge. Given the highly heterogeneous nature and the compartmentalization of the cell, different approaches are needed to control the self-assembly within the crowded intricate cellular environment. Herein, we report for the first time the self-assembly mechanism of an anthracene-guanidine derivative (AG) forming the rare and highly emissive T-shaped dimer in breast cancer cell lines as a proof of concept. This process is highly sensitive to the local environment in terms of polarity, viscosity, and/or water quantity that should enable the use of the AG as a fluorescence lifetime imaging biosensor for intracellular imaging of cellular structures and the monitoring of intracellular state parameters. Different populations of the monomer and T-shaped and π-π dimers were observed in the cell membrane, cytoplasm, and nucleoplasm, related to the local viscosity and presence of water. The T-shaped dimer is formed preferentially in the nucleus because of the higher density and viscosity compared to the cytoplasm. The present results should serve as a precursor for the development of new design strategies for molecular systems for a wide range of applications such as cell viscosity, density, or temperature sensing and imaging.

Guanylation Reactions for the Rational Design of Cancer Therapeutic Agents.

The modular synthesis of the guanidine core by guanylation reactions using commercially available ZnEt2 as a catalyst has been exploited as a tool for the rapid development of antitumoral guanidine candidates. Therefore, a series of phenyl-guanidines were straightforwardly obtained in very high yields. From the in vitro assessment of the antitumoral activity of such structurally diverse guanidines, the guanidine termed ACB3 has been identified as the lead compound of the series. Several biological assays, an estimation of AMDE values, and an uptake study using Fluorescence Lifetime Imaging Microscopy were conducted to gain insight into the mechanism of action. Cell death apoptosis, induction of cell cycle arrest, and reduction in cell adhesion and colony formation have been demonstrated for the lead compound in the series. In this work, and as a proof of concept, we discuss the potential of the catalytic guanylation reactions for high-throughput testing and the rational design of guanidine-based cancer therapeutic agents.

Enhanced Antitumoral Activity of Encapsulated BET Inhibitors When Combined with PARP Inhibitors for the Treatment of Triple-Negative Breast and Ovarian Cancers.

BRCA1/2 protein-deficient or mutated cancers comprise a group of aggressive malignancies. Although PARPis have shown considerably efficacy in their treatment, the widespread use of these agents in clinical practice is restricted by various factors, including the development of acquired resistance due to the presence of compensatory pathways. BETis can completely disrupt the HR pathway by repressing the expression of BRCA1 and could be aimed at generation combination regimes to overcome PARPi resistance and enhance PARPi efficacy. Due to the poor pharmacokinetic profile and short half-life, the first-in-class BETi JQ1 was loaded into newly developed nanocarrier formulations to improve the effectivity of olaparib for the treatment of BRCAness cancers. First, polylactide polymeric nanoparticles were generated by double emulsion. Moreover, liposomes were prepared by ethanol injection and evaporation solvent method. JQ1-loaded drug delivery systems display optimal hydrodynamic radii between 60 and 120 nm, with a very low polydispersity index (PdI), and encapsulation efficiencies of 92 and 16% for lipid- and polymeric-based formulations, respectively. Formulations show high stability and sustained release. We confirmed that all assayed JQ1 formulations improved antiproliferative activity compared to the free JQ1 in models of ovarian and breast cancers. In addition, synergistic interaction between JQ1 and JQ1-loaded nanocarriers and olaparib evidenced the ability of encapsulated JQ1 to enhance antitumoral activity of PARPis.

Ionogels Derived from Fluorinated Ionic Liquids to Enhance Aqueous Drug Solubility for Local Drug Administration.

Gelatin is a popular biopolymer for biomedical applications due to its harmless impact with a negligible inflammatory response in the host organism. Gelatin interacts with soluble molecules in aqueous media as ionic counterparts such as ionic liquids (ILs) to be used as cosolvents to generate the so-called Ionogels. The perfluorinated IL (FIL), 1-ethyl-3-methylpyridinium perfluorobutanesulfonate, has been selected as co-hydrosolvent for fish gelatin due to its low cytotoxicity and hydrophobicity aprotic polar structure to improve the drug aqueous solubility. A series of FIL/water emulsions with different FIL content and their corresponding shark gelatin/FIL Ionogel has been designed to enhance the drug solubility whilst retaining the mechanical structure and their nanostructure was probed by simultaneous SAXS/WAXS, FTIR and Raman spectroscopy, DSC and rheological experiments. Likewise, the FIL assisted the solubility of the antitumoural Doxorubicin whilst retaining the performing mechanical properties of the drug delivery system network for the drug storage as well as the local administration by a syringe. In addition, the different controlled release mechanisms of two different antitumoral such as Doxorubicin and Mithramycin from two different Ionogels formulations were compared to previous gelatin hydrogels which proved the key structure correlation required to attain specific therapeutic dosages.

Shedding light on the binding mechanism of kinase inhibitors BI-2536, Volasetib and Ro-3280 with their pharmacological target PLK1.

In the present work, the interactions of the novel kinase inhibitors BI-2536, Volasetib (BI-6727) and Ro-3280 with the pharmacological target PLK1 have been studied by fluorescence spectroscopy and molecular dynamics calculations. High Stern-Volmer constants were found in fluorescence experiments suggesting the formation of stable protein-ligand complexes. In addition, it was observed that the binding constant between BI-2536 and PLK1 increases about 100-fold in presence of the phosphopeptide Cdc25C-p that docks to the polo box domain of the protein and releases the kinase domain. All the determined binding constants are higher for the kinase inhibitors than for their competitor for the active center (ATP) being BI-2536 and Volasertib the inhibitors that showed more affinity for PLK1. Calculated binding free energies confirmed the higher affinity of PLK1 for BI-2536 and Volasertib than for ATP. The higher affinity of the inhibitors to PLK1 compared to ATP was mainly attributed to stronger van der Waals interactions. Results may help with the challenge of designing and developing new kinase inhibitors more effective in clinical cancer therapy.

Multifunctional PLA/Gelatin Bionanocomposites for Tailored Drug Delivery Systems.

A series of bionanocomposites composed of shark gelatin hydrogels and PLA nanoparticles featuring different nanostructures were designed to generate multifunctional drug delivery systems with tailored release rates required for personalized treatment approaches. The global conception of the systems was considered from the desired customization of the drug release while featuring the viscoelastic properties needed for their ease of storage and posterior local administration as well as their biocompatibility and cell growth capability for the successful administration at the biomolecular level. The hydrogel matrix offers the support to develop a direct thermal method to convert the typical kinetic trapped nanostructures afforded by the formulation method whilst avoiding the detrimental nanoparticle agglomeration that diminishes their therapeutic effect. The nanoparticles generated were successfully formulated with two different antitumoral compounds (doxorubicin and dasatinib) possessing different structures to prove the loading versatility of the drug delivery system. The bionanocomposites were characterized by several techniques (SEM, DLS, RAMAN, DSC, SAXS/WAXS and rheology) as well as their reversible sol-gel transition upon thermal treatment that occurs during the drug delivery system preparation and the thermal annealing step. In addition, the local applicability of the drug delivery system was assessed by the so-called "syringe test" to validate both the storage capability and its flow properties at simulated physiological conditions. Finally, the drug release profiles of the doxorubicin from both the PLA nanoparticles or the bionanocomposites were analyzed and correlated to the nanostructure of the drug delivery system.

Characterization of Tuna Gelatin-Based Hydrogels as a Matrix for Drug Delivery.

The skin of yellowfin tuna is one of the fishery industry solid residues with the greatest potential to add extra value to its circular economy that remains yet unexploited. Particularly, the high collagen content of fish skin allows generating gelatin by hydrolysis, which is ideal for forming hydrogels due to its biocompatibility and gelling capability. Hydrogels have been used as drug carriers for local administration due to their mechanical properties and drug loading capacity. Herein, novel tuna gelatin hydrogels were designed as drug vehicles with two structurally different antitumoral model compounds such as Doxorubicin and Crocin to be administrated locally in tissues with complex human anatomies after surgical resection. The characterization by gel permeation chromatography (GPC) of purified gelatin confirmed their heterogeneity composition, exhibiting three major bands that correspond to the ß and α chains along with high molecular weight species. In addition, the Fourier Transform Infrared (FT-IR) spectra of gelatin probed the secondary structure of the gelatin showing the simultaneous existence of α helix, ß sheet, and random coil structures. Morphological studies at different length scales were performed by a multi-technique approach using SAXS/WAXS, AFM and cryo-SEM that revealed the porous network formed by the interaction of gelatin planar aggregates. In addition, the sol-gel transition, as well as the gelation point and the hydrogel strength, were studied using dynamic rheology and differential scanning calorimetry. Likewise, the loading and release profiles followed by UV-visible spectroscopy indicated that the novel gelatin hydrogels improve the drug release of Doxorubicin and Crocin in a sustained fashion, indicating the structure-function importance in the material composition.

Mithramycin delivery systems to develop effective therapies in sarcomas.

BACKGROUND: Sarcomas comprise a group of aggressive malignancies with very little treatment options beyond standard chemotherapy. Reposition of approved drugs represents an attractive approach to identify effective therapeutic compounds. One example is mithramycin (MTM), a natural antibiotic which has demonstrated a strong antitumour activity in several tumour types, including sarcomas. However, its widespread use in the clinic was limited by its poor toxicity profile. RESULTS: In order to improve the therapeutic index of MTM, we have loaded MTM into newly developed nanocarrier formulations. First, polylactide (PLA) polymeric nanoparticles (NPs) were generated by nanoprecipitation. Also, liposomes (LIP) were prepared by ethanol injection and evaporation solvent method. Finally, MTM-loaded hydrogels (HG) were obtained by passive loading using a urea derivative non-peptidic hydrogelator. MTM-loaded NPs and LIP display optimal hydrodynamic radii between 80 and 105 nm with a very low polydispersity index (PdI) and encapsulation efficiencies (EE) of 92 and 30%, respectively. All formulations show a high stability and different release rates ranging from a fast release in HG (100% after 30 min) to more sustained release from NPs (100% after 24 h) and LIP (40% after 48 h). In vitro assays confirmed that all assayed MTM formulations retain the cytotoxic, anti-invasive and anti-stemness potential of free MTM in models of myxoid liposarcoma, undifferentiated pleomorphic sarcoma and chondrosarcoma. In addition, whole genome transcriptomic analysis evidenced the ability of MTM, both free and encapsulated, to act as a multi-repressor of several tumour-promoting pathways at once. Importantly, the treatment of mice bearing sarcoma xenografts showed that encapsulated MTM exhibited enhanced therapeutic effects and was better tolerated than free MTM. CONCLUSIONS: Overall, these novel formulations may represent an efficient and safer MTM-delivering alternative for sarcoma treatment.

New titanocene derivative with improved stability and binding ability to albumin exhibits high anticancer activity.

Titanium-based therapies have emerged as a promising alternative for the treatment of cancer patients, particularly those with cisplatin resistant tumors. Unfortunately, some titanium compounds show stability and solubility problems that have hindered their use in clinical practice. Here, we designed and synthesized a new titanium complex containing a titanocene fragment, a tridentate ligand to improve its stability in water, and a long aliphatic chain, designed to facilitate a non-covalent interaction with albumin, the most abundant protein in human serum. The stability and human serum albumin affinity of the resulting titanium complex was investigated by UV-Vis absorption and fluorescence spectroscopy techniques. Complex [TiCp2{(OOC)2py-O-myr}] (3) (myr = C14H29, py = pyridine) and its analogous [TiCp2{(OOC)2py-OH}] (4), lacking the aliphatic chain, showed improved stability in phosphate saline buffer compared with [TiCp2Cl2] (1). 3 showed a strong interaction with human serum albumin in a 1:1 stoichiometry. The cytotoxic effect of 3 was higher compared to [TiCp2Cl2] in tumor cell lines and showed potential tumor selectivity when assayed in non-tumor human epithelial cells. Finally, 3 showed an antiproliferative effect on cancer cells, decreasing the population in the S phase, and increasing apoptotic cells in a significant manner. All this makes the novel Ti(IV) compound 3 a firm candidate to continue further studies of its therapeutic potential in vitro and in vivo.

Polyester Polymeric Nanoparticles as Platforms in the Development of Novel Nanomedicines for Cancer Treatment.

Many therapeutic agents have failed in their clinical development, due to the toxic effects associated with non-transformed tissues. In this context, nanotechnology has been exploited to overcome such limitations, and also improve navigation across biological barriers. Amongst the many materials used in nanomedicine, with promising properties as therapeutic carriers, the following one stands out: biodegradable and biocompatible polymers. Polymeric nanoparticles are ideal candidates for drug delivery, given the versatility of raw materials and their feasibility in large-scale production. Furthermore, polymeric nanoparticles show great potential for easy surface modifications to optimize pharmacokinetics, including the half-life in circulation and targeted tissue delivery. Herein, we provide an overview of the current applications of polymeric nanoparticles as platforms in the development of novel nanomedicines for cancer treatment. In particular, we will focus on the raw materials that are widely used for polymeric nanoparticle generation, current methods for formulation, mechanism of action, and clinical investigations.

Controlled Delivery of BET-PROTACs: In Vitro Evaluation of MZ1-Loaded Polymeric Antibody Conjugated Nanoparticles in Breast Cancer.

Bromo and extraterminal domain (BET) inhibitors-PROteolysis TArgeting Chimera (BETi-PROTAC) is a new family of compounds that induce proteasomal degradation through the ubiquitination of the tagged to BET inhibitors Bromodomain proteins, BRD2 and BRD. The encapsulation and controlled release of BET-PROTACs through their vectorization with antibodies, like trastuzumab, could facilitate their pharmacokinetic and efficacy profile. Antibody conjugated nanoparticles (ACNPs) using PROTACs have not been designed and evaluated. In this pioneer approach, the commercial MZ1 PROTAC was encapsulated into the FDA-approved polymeric nanoparticles. The nanoparticles were conjugated with trastuzumab to guide the delivery of MZ1 to breast tumoral cells that overexpress HER2. These ACNPs were characterized by means of size, polydispersity index, and Z-potential. Morphology of the nanoparticles, along with stability and release studies, completed the characterization. MZ1-loaded ACNPs showed a significant cytotoxic effect maintaining its mechanism of action and improving its therapeutic properties.

Antibody Conjugation of Nanoparticles as Therapeutics for Breast Cancer Treatment.

Breast cancer is the most common invasive tumor in women and the second leading cause of cancer-related death. Nanomedicine raises high expectations for millions of patients as it can provide better, more efficient, and affordable healthcare, and it has the potential to develop novel therapeutics for the treatment of solid tumors. In this regard, targeted therapies can be encapsulated into nanocarriers, and these nanovehicles are guided to the tumors through conjugation with antibodies-the so-called antibody-conjugated nanoparticles (ACNPs). ACNPs can preserve the chemical structure of drugs, deliver them in a controlled manner, and reduce toxicity. As certain breast cancer subtypes and indications have limited therapeutic options, this field provides hope for the future treatment of patients with difficult to treat breast cancers. In this review, we discuss the application of ACNPs for the treatment of this disease. Given the fact that ACNPs have shown clinical activity in this clinical setting, special emphasis on the role of the nanovehicles and their translation to the clinic is placed on the revision.

An Overview of Antibody Conjugated Polymeric Nanoparticles for Breast Cancer Therapy.

Nanoparticles (NPs) are promising drug delivery systems (DDS) for identifying and treating cancer. Active targeting NPs can be generated by conjugation with ligands that bind overexpressed or mutant cell surface receptors on target cells that are poorly or not even expressed on normal cells. Receptor-mediated endocytosis of the NPs occurs and the drug is released inside the cell or in the surrounding tissue due to the bystander effect. Antibodies are the most frequently used ligands to actively target tumor cells. In this context, antibody-based therapies have been extensively used in HER2+ breast cancer. However, some patients inherently display resistance and in advanced stages, almost all eventually progress. Functionalized NPs through conjugation with antibodies appear to be a promising strategy to optimize targeted therapies due to properties related to biocompatibility, suitable delivery control and efficiency of functionalization. This review is focused on the different strategies to conjugate antibodies into polymeric NPs. Recent antibody conjugation approaches applied to the improvement of breast cancer therapy are highlighted in this review.

Functionalized CdSe/ZnS Quantum Dots for Intracellular pH Measurements by Fluorescence Lifetime Imaging Microscopy.

pH is an important biomarker for many human diseases and great efforts are being made to develop new pH probes for bioimaging and biomedical applications. Here, the use of three different CdSe/ZnS QDs, functionalized with d-penicillamine and small peptides, as pH probes for fluorescence lifetime imaging microscopy (FLIM) is investigated. The fluorescence pH sensitivity of the nanoparticles is analyzed in different experimental media: aqueous solution, synthetic intracellular medium, and mesenchymal C3H10T1/2 and tumoral SK-MEL-2 cell lines. Different experiments along with theoretical calculations are conducted to unravel the mechanisms causing pH sensitivity of the nanoparticles and the effect of the length and composition of the peripheral branches on their photophysical properties. Absolute intracellular pH values measured in live cells with FLIM using a fluorescent probe based on a QD are reported here for the first time (intracellular pH values of 7.0 and 7.1 for C3H10T1/2 and SK-MEL-2 cells, respectively). These fluorescent nanoprobes can also be used to distinguish between different types of cells in cocultures on the basis of their different fluorescence lifetimes in dissimilar intracellular environments.

Screening and Preliminary Biochemical and Biological Studies of [RuCl(p-cymene)(N,N-bis(diphenylphosphino)-isopropylamine)][BF4] in Breast Cancer Models.

Breast cancer is the second leading cause of cancer death worldwide. Despite progress in drug discovery, identification of the correct population is the limiting factor to develop new compounds in the clinical setting. Therefore, the aim of this study is to evaluate the effects of a new metallodrug, [RuCl(p-cymene)(N,N-bis(diphenylphosphino)-isopropylamine)][BF4] (pnpRu-14), as a lead pnp-Ru compound by screening and preliminary biochemical and biological studies in different breast cancer subtypes. The results show that complex pnpRu-14 is much more effective in promoting in vitro cytotoxic effects on HER2+ and RH+/HER2- breast cancer than the reference metallodrugs cisplatin, carboplatin, or RAPTA-C. It is important to highlight that pnpRu-14 shows an impressive cytotoxicity against BT474 cells. Caspase-dependent apoptosis is the mechanism of action for these compounds. In addition, treatment of SKBR3, BT474, T47D, and MCF7 cancer cells with pnpRu-14 caused an accumulation of cells in the G0/G1 phase cells. The human serum albumin, DNA, and H1 histones binding properties of the lead compound are reported. Pharmacokinetic and biodistribution studies show a quick absorption of pnpRu-14 in serum with no significant accumulation in any of the tested organs. This work provides evidence to support the preclinical and clinical development of pnpRu-14 in breast cancer.

Poly(Cyclohexene Phthalate) Nanoparticles for Controlled Dasatinib Delivery in Breast Cancer Therapy.

The effect on the activity in breast cancer models of the small tyrosine kinase inhibitor dasatinib (DAS), either alone or in combination with other antitumoral agents, has been recently explored. However, DAS is characterized by its low and highly pH-dependent solubility, which could lead to poor uptake of the drug limiting its tumoral efficacy. Thus far, the development of safe and efficient delivery vehicles of DAS to improve the therapeutic efficacy minimizing the toxicity profile is still required. In this work, a biodegradable and biocompatible polyester is assessed, for the first time, as raw material for the generation of polymeric nanoparticles (NPs). NPs of 100 nm with a narrow polydispersity were formulated for the encapsulation of DAS. The enzymatic and cellular degradation of the new drug delivery system has been studied, and the toxicity and blood compatibility evaluated for its potential clinical use. The new material used for the generation of nanoparticles led to encapsulate DAS in an efficient manner with quicker release DAS profile when compared with the FDA-approved biopolymer Polylactide. The new DAS-loaded polymeric nanocarrier gave a superior efficacy when compared to free DAS with no difference in the mechanism of action. The new NPs shown to be a promising DAS delivery system to be further evaluated for breast cancer treatment.

Assessment of doxorubicin delivery devices based on tailored bare polycaprolactone against glioblastoma.

Bare polycaprolactones with controlled molar mass and dispersity were employed to manufacture biodegradable devices, which were applied for doxorubicin delivery in glioblastoma. Micro- and nanoscale devices were prepared by emulsion formation or by a combination of precipitation and hydrolysis. The carriers were characterized by scanning electron microscopy, dynamic light scattering techniques, thermogravimetric analysis and differential scanning calorimetry. The encapsulation parameters and drug-release profiles are discussed in order to evaluate the influence of different fundamental parameters, such as molar mass and dispersity value, pH, morphology or crystallinity, on the efficiency of the doxorubicin delivery systems. The ability of doxorubicin-loaded micro- and nanoscale devices to induce cellular toxicity in glioblastoma cells was also explored. A cell viability assay against C6 cells of doxorubicin-loaded nanocarriers showed higher cytotoxicity than doxorubicin-loaded microcarriers. In addition, doxorubicin-loaded nanocarriers also showed good antitumor profile in human tumoral cells and improved the security profile in relation to free doxorubicin in non-tumoral cells. Consistent with the assessment study described in this manuscript, the results provide a proof of concept for the suitability of the approach, based on bare polycaprolactone, to local controlled-sustained release of doxorubicin for the treatment of glioblastoma.

Trastuzumab-Targeted Biodegradable Nanoparticles for Enhanced Delivery of Dasatinib in HER2+ Metastasic Breast Cancer.

Dasatinib (DAS) is a multikinase inhibitor that acts on several signaling kinases. DAS is used as a second-line treatment for chronic accelerated myeloid and Philadelphia chromosome-positive acute lymphoblastic leukemia. The therapeutic potential of DAS in other solid tumours is under evaluation. As for many other compounds, an improvement in their pharmacokinetic and delivery properties would potential augment the efficacy. Antibody-targeted biodegradable nanoparticles can be useful in targeted cancer therapy. DAS has shown activity in human epidermal growth factor receptor 2 (HER2) positive tumors, so conjugation of this compound with the anti-HER2 antibody trastuzumab (TAB) with the use of nanocarriers could improve its efficacy. TAB-targeted DAS-loaded nanoparticles were generated by nanotechnology. The guided nanocarriers enhanced in vitro cytotoxicity of DAS against HER2 human breast cancer cell lines. Cellular mechanistic, release studies and nanoparticles stability were undertaken to provide evidences for positioning DAS-loaded TAB-targeted nanoparticles as a potential strategy for further development in HER2-overexpressing breast cancer therapy.