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Fourier transform‐infrared spectra of different components and formulations. DOPE, 1,2‐dioleoyl‐sn‐glycero‐3‐phosphoethanolamine; mAb, monoclonal antibody
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Abstract Epirubicin (EPI) is one of the potent breast cancer (BC) chemotherapeutic agents, but its adverse effects limit its efficacy. Herein, EPI was selected to be loaded in liposomal carrier, which has been targeted by a monoclonal antibody, Herceptin. The preparation process of liposomes was a modified ethanol injection method followed by Herce...
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Human epidermal growth factor receptor 2 (HER2) proteins are overexpressed in a certain proportion of gastric cancer cases. Trastuzumab is a humanized monoclonal antibody that targets the HER2 receptor. Previous studies have demonstrated a synergistic interaction between trastuzumab and 5-fluorouracil/cisplatin in HER2-positive gastric cancer cells...
Background
Although dual blockade HER2-based neoadjuvant chemotherapy is associated with excellent outcomes for human epidermal growth factor receptor 2 (HER2)-positive breast cancer, pertuzumab is not available to all patients due to cost. The optimal neoadjuvant chemotherapy for HER2-positive breast cancer in the presence of a single HER2 blockad...
Background
Neoadjuvant chemotherapy (NAC) has been expanded to hormone receptor (HR) positive breast cancer (BC) patients with operable disease, to increase the likelihood of breast-conserving surgery. Genomic profiling at baseline would reveal NAC response relevant genomic features and signaling pathways, guiding clinical NAC utilization based on...
Citations
... A little differently, Khaleseh et al. [85] concluded that TZM-conjugated liposomes (immunoliposomes) had been formed based on FTIR and differential scanning calorimetry (DSC) findings, namely, the observation of the endothermic peak of TZM in the thermogram of the immunoliposomes. ...
The specific interaction between cell surface receptors and corresponding antibodies has driven opportunities for developing targeted cancer therapies using nanoparticle systems. It is challenging to design and develop such targeted nanomedicines using antibody ligands, as the final nanoconjugate’s specificity hinges on the cohesive functioning of its components. The multicomponent nature of antibody-conjugated nanoparticles also complicates the characterization process. Regardless of the type of nanoparticle, it is essential to perform physicochemical characterization to establish a solid foundation of knowledge and develop suitable preclinical studies. A meaningful physicochemical evaluation of antibody-conjugated nanoparticles should include determining the quantity and orientation of the antibodies, confirming the antibodies’ integrity following attachment, and assessing the immunoreactivity of the obtained nanoconjugates. In this review, the authors describe the various techniques (electrophoresis, spectroscopy, colorimetric assays, immunoassays, etc.) used to analyze the physicochemical properties of nanoparticles functionalized with antibodies and discuss the main results.
... Epirubicin (EPI), or 4'epidoxorubicin, is a chemotherapeutic agent belonging to the family of anthracyclines. It is effective against several cancers, including carcinoma, small cell lung carcinoma, ovarian cancer, gastric cancer, and non-Hodgkin's lymphoma (Khaleseh et al. 2021). EPI exhibits its antineoplastic effect by DNA intercalation, thus inhibiting the biosynthesis of DNA and RNA (Hemati Azandaryani et al. 2018) and stabilising the topoisomerase-DNA cleavable complex. ...
Epirubicin (EPI) is an effective chemotherapeutic against breast cancer, though EPI-related cardiotoxicity limits its usage. Endogenously derived 3-indolepropionic acid (3-IPA) from tryptophan metabolism is of interest due to its antioxidant capabilities which may have cardioprotective effects. Supplementation with 3-IPA may abate EPI's cardiotoxicity, and herein we studied the possibility of lessening EPI-induced cardiotoxicity in Wistar rats. Experimental rats (n = 30; BW 180–200 g) were randomly distributed in five cohorts (A–E; n = 6 each). Group A (control), Group B (EPI 2.5 mg/mL), and group C (3-IPA 40 mg/kg) while Groups D and E were co-treated with EPI (2.5 mg/mL) together with 3-IPA (D: 20 and E: 40 mg/kg). Following sacrifice, oxidative status, lipid profile, transaminases relevant to cardiac function, and inflammatory biomarkers were analysed. Also, 8-hydroxyl-2'-deoxyguanosine (8-OHdG) and cardiac troponin T (cTnT) levels were assessed using an enzyme-linked immunosorbent assay (ELISA). EPI-initiated increases in cardiotoxicity biomarkers were significantly (p < 0.05) reduced by 3-IPA supplementation. Decreased antioxidant and increases in reactive oxygen and nitrogen species (RONS), 8-OHdG and lipid peroxidation were lessened (p < 0.05) in rat hearts co-treated with 3-IPA. EPI-induced increases in nitric oxide and myeloperoxidase were reduced (p < 0.05) by 3-IPA co-treatment. In addition, 3-IPA reversed EPI-mediated alterations in alanine aminotransferase (ALT), aspartate amino transaminases (AST), lactate dehydrogenase (LDH), cardiac troponin T (cTnT), and serum lipid profile including total cholesterol and triglycerides. Microscopic examination of the cardiac tissues showed that histopathological lesions severity induced by EPI was lesser in 3-IPA co-treated rats. Our findings demonstrate that supplementing endogenously derived 3-IPA can enhance antioxidant protection in the cardiac tissue susceptible to EPI toxicity in female rats. These findings may benefit breast cancer patients undergoing chemotherapy by further validating these experimental data.
... Also known as ErbB2 or CD340, HER2 regulates cell growth and proliferation and is one of the most used surface receptors to target liposomes for breast cancer and others, such as prostate cancer [68]. A growing number of therapeutic agents, namely bleomycin [69], DTX [70,71], curcumin and resveratrol [72], idarubicin [73], and epirubicin [74], have been proposed as payloads in breast cancer targeting, using TZM-conjugated liposomes. With liposomes linked to listeriolysin O and TZM, the amount of bleomycin needed to reduce tumor cell growth and viability is nearly 57,000-fold lower than the concentration required if the drug is administered extracellularly [69]. ...
... By coating liposomes with TZM, there was a dramatic increase in the antiproliferative effects of curcumin and resveratrol in HER2-overexpressing breast cancer cells [72]. The works by Amin et al. [73] and Khaleseh et al. [74] showed that such a drug delivery system could be a good choice for anthracyclines as well and provided a promising background for further in vivo studies. ...
Nanotechnology takes the lead in providing new therapeutic options for cancer patients. In the last decades, lipid-based nanoparticles—solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), liposomes, and lipid–polymer hybrid nanoparticles—have received particular interest in anticancer drug delivery to solid tumors. To improve selectivity for target cells and, thus, therapeutic efficacy, lipid nanoparticles have been functionalized with antibodies that bind to receptors overexpressed in angiogenic endothelial cells or cancer cells. Most papers dealing with the preclinical results of antibody-conjugated nanoparticles claim low systemic toxicity and effective tumor inhibition, which have not been successfully translated into clinical use yet. This review aims to summarize the current “state-of-the-art” in anticancer drug delivery using antibody-functionalized lipid-based nanoparticles. It includes an update on promising candidates that entered clinical trials and some explanations for low translation success.
... Also, the decrease in vibrations of C-H and C--O groups to 1600 cm − 1 and 1416 cm − 1 in the PVA after conjugation with silver was mentioned in other reports [55]. Fig. 5 (c) shows the FT-IR analysis of EPI where the peak around 3500 cm − 1 is related to the OH and NH 2 groups and the peak at 1600 cm − 1 is related to C--O between the two aromatic rings [56]. Fig. 5 (d) shows the FT-IR of EPI/PVA/AgNPs where the stretching vibrational peak of OH was shifted to 3250 cm − 1 and its intensity was decreased. ...
The current study highlights the effective role of silver nanoparticles in improving the tumor targeting efficiency of epirubicin, chemotherapeutic agent. Regarding this, poly (vinyl alcohol)-coated silver nanoparticles were designed in a particle size of 18 ± 0.1 nm. Furthermore, poly (vinyl alcohol)-coated silver nanoparticles were conjugated with epirubicin in a conjugation efficiency of 88 ± 2%. Moreover, both poly (vinyl alcohol)-coated silver nanoparticles and epirubicin-conjugated poly (vinyl alcohol)-coated silver nanoparticles were radioiodinated using iodine-131 isotope and yielded 90.6 ± 0.1% and 80 ± 2%, respectively. Crucially, the comparative in-vivo distribution of radioiodinated poly (vinyl alcohol)-coated silver nanoparticles and epirubicin-conjugated poly (vinyl alcohol)-coated silver nanoparticles were studied in healthy and tumor models. Interestingly, the radioiodinated epirubicin-conjugated poly (vinyl alcohol)-coated silver nanoparticles exhibited reticuloendothelial system (RES) shirking and prolonged blood concentration. In addition, it targeted tumor site by 22.8 ± 1% ID/g within 1 h post IV injection. Further, the tumor targeting efficiency of the new systemwas confirmed by calculating the tumor to normal tissue and the tumor to blood ratios were 12.67 ± 0.5 and 1.74 ± 0.05, respectively at 1 h post IV injection. Consequently, the findings provided the radioiodinated epirubicin-conjugated poly (vinyl alcohol)-coated silver nanoparticles as a new potential approach for tumor targeting with a goal of treatment and/or imaging.
... These findings were encouraging as the higher the value of zeta potential, the lower the aggregation and the greater the stability of the NPs (Soheyla and Foruhe, 2013). Fig. 4 (a) shows the FT-IR spectrum of EPI where the peak at 1600 cm − 1 is related to C--O between the two aromatic rings and the peak around 3500 cm − 1 is related to the OH and NH 2 groups (Khaleseh, 2021). Fig. 4 (b) shows the FT-IR of PEG, PEG/AgNPs and EPI/PEG/ AgNPs. ...
This work highlights boosting the tumor targeting efficiency of epirubicin through loading on a new radio-nanosystem, based on the effective role of silver nanoparticles (AgNPs). Accordingly, PEGylated silver nano-particles (PEG/AgNPs) were prepared in a size of 20.2 ± 0.1 nm. Additionally, epirubicin was loaded on PEG/ AgNPs with a loading efficiency of 63 ± 3 %. Furthermore, both of PEG/AgNPs and EPI/PEG/AgNPs were radiolabeled with 131 I isotope with radiolabeling yields of 85 ± 0.2 % and 90.3 ± 1 %, respectively. The in-vivo distribution of 131 I-PEG/AgNPs and 131 I-EPI/PEG/AgNPs were examined in healthy and tumor bearing mice models. Excitingly, 131 I-EPI/PEG/AgNPs revealed a reticuloendothelial system (RES) avoidance and prolonged circulating time. In addition, 131 I-EPI/PEG/AgNPs showed fast targeting of tumor site by 25.1 ± 0.1 %ID/g within 0.5 h after intravenous injection. Subsequently, the outcomes provided 131 I-EPI/PEG/AgNPs as a new potential system for enhancement of tumor targeting and theranosis (therapy and/or imaging).
Because of their high specificity, high affinity, and targeting, antibody drugs have been widely used in the treatment of many diseases and have become the most favored new drugs for research in the world. However, some antibody drugs (such as small-molecule antibody fragments) have a short half-life and need to be administered frequently, and are often associated with injection-site reactions and local toxicities during use. Increasing attention has been paid to the development of antibody drugs that are long-acting and have fewer side effects. This paper reviews existing strategies to achieve long-acting antibody drugs, including modification of the drug structure, the application of drug delivery systems, and changing their administration route. Among these, microspheres have been studied extensively regarding their excellent tolerance at the injection site, controllable loading and release of drugs, and good material safety. Subcutaneous injection is favored by most patients because it can be quickly self-administered. Subcutaneous injection of microspheres is expected to become the focus of developing long-lasting antibody drug strategies in the near future.
Targeted therapies using nanoparticles have been proposed to address some drawbacks of conventional chemotherapy. In the last two decades, surface modification of nanoparticles with antibody ligands has been extensively explored for the safe and effective delivery of chemotherapeutic drugs. By capitalizing on receptors overexpressed on cancer cells or angiogenic endothelial cells, antibody-functionalized nanoparticles are promising candidates to improve selectivity for target cells and, thus, therapeutic efficacy. This work offers a brief overview of nanotechnology applied to targeted cancer therapies and highlights the use of antibodies as targeting ligands. After presenting a summary of the most common methods for nanoparticle functionalization with antibodies, the authors discuss different targeting strategies divided into angiogenesis-associated targeting, uncontrolled cell proliferation targeting, and tumor cell targeting. Special emphasis is given to antibody-nanoparticle conjugates that have entered the clinical testing phase. Some explanations for the discrepancy between preclinical and clinical observations are also provided.
Targeted drug and gene delivery is the key for precision therapy. Lipid nanoparticles as non-viral vectors have attracted extensive attentions in treating a variety of diseases, such as cancer, immune disease, cardiac diseases and pathogen infection. They exhibit low immunogenicity and low cytotoxicity, which make them as the most-commonly used vectors. More importantly, their surfaces could be functionalized, which provide a platform to improve targeting and pharmacokinetic/pharmacodynamic properties. Although there has been great success to synthesize lipid nanoparticles, it remains as a challenge to produce active targeting lipid nanoparticles especially with definable targetability, high quality and good translation reproducibility. This review focus on the techniques to fabricate active targeting lipid nanoparticles. We start with a brief introduction of targeting lipid nanoparticles, followed by a focused discussion of various preparation approaches including one-pot assembly and post-insertion functionalization. The methods, mechanism and representative examples are introduced, together with the comparison of their advantages and restrictions. Finally, challenges facing formulation screening and clinical translation are discussed.
