Abstract:
BACKGROUND:Liposomes have been employed to improve pharmacokinetics and reduce side effects of drugs. They can be functionalized with antibodies for targeted delivery. While the monoclonal antibody trastuzumab has been employed in the therapy of HER2-positive breast cancer, the resistance developed during treatment has been reported. Rapamycin could be used in combination with trastuzumab for improved therapeutic response. OBJECTIVE:In this study, we aimed to develop rapamycin-loaded liposomes and immunoliposomes with trastuzumab, characterize them and evaluate their in vitro cytotoxicity. METHOD:Formulations were prepared by the thin film hydration method and immunoliposome was conjugated to antibody by covalent bond. Characterization involved particle size, polydispersity, zeta potential, encapsulation efficiency, functionalization efficiency, DSC and FTIR assays. Cell studies were conducted through the MTT assay. RESULTS:SPC:Chol:DSPE-PEG formulation prepared at 1:10 drug to lipid ratio presented high encapsulation efficiency, appropriate particle size, low polydispersity, negative zeta potential and colloidal stability. Rapamycin exhibited intermolecular interactions with lipids and underwent crystallinity reduction. Rapamycin-loaded immunoliposomes were prepared with high trastuzumab functionalization efficiency and antibody stability. Cytotoxicity studies showed that the HER2-positive SK-BR-3 cell line was sensitive to trastuzumab, either as free drug or in the context of immunoliposomes, and is more sensitive to rapamycin than the triple negative MDA-MB-231 cells. For MDA-MB-231, the liposomal rapamycin was more cytotoxic than the free drug. Furthermore, the immunoliposomes showed potent cytotoxicity against SK-BR-3 cells. Finally, rapamycin and trastuzumab exhibited in vitro synergistic effect, particularly through immunoliposomes. CONCLUSION:The formulation developed herein has potential for in vivo evaluation.
journal_name
Anticancer Agents Med Chemjournal_title
Anti-cancer agents in medicinal chemistryauthors
Eloy JO,Petrilli R,Brueggemeier RW,Marchetti JM,Lee RJsubject
Has Abstractpub_date
2017-01-01 00:00:00pages
48-56issue
1eissn
1871-5206issn
1875-5992pii
ACAMC-EPUB-75952journal_volume
17pub_type
杂志文章abstract::Histone deacetylase inhibitors (HDACIs) represent one of the most promising, recently developed classes of anticancer agents already approved by the U.S. FDA. The effectiveness of these new drugs has currently being explored in a variety of cancer cell lines, in vitro, animal models, in vivo, as well as in clinical tr...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:
更新日期:2013-03-01 00:00:00
abstract::Replication fork reversal and restart has gained immense interest as a central response mechanism to replication stress following DNA damage. Although the exact mechanism of fork reversal has not been elucidated precisely, the involvement of diverse pathways and different factors has been demonstrated, which are centr...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520620666200518082433
更新日期:2020-01-01 00:00:00
abstract::Apoptosis, or programmed cell death, is an important physiologic process multicellular organisms use to maintain homeostasis by providing a means for elimination of redundant cells during development. Furthermore, cells that have become damaged or are defective undergo apoptosis to prevent disease. It is an important ...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/187152009789377763
更新日期:2009-11-01 00:00:00
abstract::Phospholipase A2 (PLA2), Cyclooxygenase (COX) and 5-Lipoxygenase (5-LOX) are arachidonic acid metabolizing enzymes and their inhibitors have been developed as therapeutic molecules for cancer and inflammation related disorders. In the present study, PLA2, COX 1&2 and 5-LOX inhibitory studies of Borassus flabellifer se...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520615666150202110936
更新日期:2015-01-01 00:00:00
abstract::Polyphenol-protein interaction (PPI) is reversible in that polyphenol-protein complex can be dissociated and release the free polyphenols. The aim of this study is to evaluate the contribution of polyphenol-protein interaction on improving the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging capacity of polyphe...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/187152012802650101
更新日期:2012-10-01 00:00:00
abstract::Sphingosine 1-phosphate (S1P) is a bioactive lipid with diverse biological functions, including cell proliferation, differentiation, angiogenesis, chemotaxis, and migration. Many of the activities of S1P are mediated through five closely related G-protein-coupled receptors of the sphingosine-1-phosphate receptor famil...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/187152011797655041
更新日期:2011-11-01 00:00:00
abstract::The systematic improvement of methods used for unraveling physiological and pathological role of proteases, as well as for elucidation of relevant hydrolase structures contributes to the progress in the area of new inhibitor-like drugs development. Many of protease inhibitors have entered clinics and are now successfu...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/187152009789056877
更新日期:2009-09-01 00:00:00
abstract::A physiologically stable thiolate gold(I) derivative [Au(Spyrimidine)(PTA-CH2Ph)]Br has shown inhibition in colon cancer proliferation of Caco-2/TC7, Caco-2/PD7 and HTC-116-luc2 cell lines via apoptotic pathway and S-phase arrest in the cell cycle. Intraperitoneal injection of [Au(Spyrimidine)(PTA-CH2Ph)]Br in athymic...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520615666150129211440
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:The existence of drug-resistance and lack of selectivity encourages scientists to search for novel and more selective cytotoxic agents. OBJECTIVES:In this work, novel 1,3,4-triarylpyrazole derivatives were synthesized to study their cytotoxicity on MCF7 (human breast Cell Line). In addition, QSAR studies we...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520619666190207094610
更新日期:2019-01-01 00:00:00
abstract::Effective elicitation of endogenous immunity is associated with improved prognosis for cancer patients. Clinical evidence in hematological and solid cancers shows that intratumoral injection of immunostimulatory genes primes and augments endogenous T cell responses. The ability of pro-inflammatory chemokines/cytokines...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/18715206113136660375
更新日期:2014-02-01 00:00:00
abstract:BACKGROUND:Intrinsic resistance to apoptotic cell death due to co-occurrence of mutated KRAS and p53 is frequently reported in pancreatic cancer that renders them aggressive, highly proliferative and metastatic. In addition, these cancer types are less sensitive to apoptosis inducing drugs where promotion of autophagic...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:The genetic heterogeneity of tumor cells and the development of therapy-resistant cancer cells in addition to the high cost necessitate the continuous development of novel targeted therapies. METHODS:In this regard, 14 novel benzoxazinone derivatives were synthesized and examined for anticancer activity aga...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520619666190201145221
更新日期:2019-01-01 00:00:00
abstract::Synthetic alkylphospholipids (APLs), exhibit similarity to the platelet-activating factor (PAF). These compounds have antiproliferative effects on tumour cells and can therefore be regarded as a new class of drugs. Unlike classic cytostatic agents, synthetic alkylphospholipids do not interfere with the DNA or the mito...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1871520614666140309222845
更新日期:2014-05-01 00:00:00
abstract::Indole compounds, found in cruciferous vegetables, are potent anti-cancer agents. Studies with indole-3-carbinol (I3C) and its dimeric product, 3,3'-diindolylmethane (DIM) suggest that these compounds have the ability to deregulate multiple cellular signaling pathways, including PI3K/Akt/mTOR signaling pathway. These ...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/18715206113139990078
更新日期:2013-09-01 00:00:00
abstract:BACKGROUND:Pyrazolo[3,4-d]pyrimidine scaffold was reported to possess potent cytotoxic and CDK2 inhibitory activity as analogue of roscovitine. OBJECTIVE:To design and synthesize novel 1-(4-flourophenyl)pyrazolo[3,4-d]pyrimidine derivatives as bioisosters of roscovitine with potential cytotoxic and CDK2 inhibitory act...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520619666190417153350
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:The network interactions link human disease proteins to regulatory cellular pathways leading to better understanding of protein functions and cellular processes. Revealing the network of signaling pathways in cancer through protein-protein interactions at molecular level enhances our understanding of Hepatoc...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520618666180507141632
更新日期:2018-01-01 00:00:00
abstract::A number of N-alkylated 4-anilinofuro[2,3-b]quinoline derivatives were synthesized and evaluated in vitro against PC-3, A549, and MCF-7 cancer cells and M-10 normal human mammary epithelial cells. The known antimitotic CIL-102 was moderately active against the growth of PC-3 prostate cancer cells with an IC50 value of...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520615666150121122700
更新日期:2015-01-01 00:00:00
abstract::Organic sulfur compounds (OSCs) derived from plants, fungi or bacteria can serve as chemopreventive and/or chemotherapeutic agents and have been attracting medical and research interest as a promising source for novel anti-cancer agents. Garlic, which has long been used as a medicinal plant in different cultures due t...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/187152011795347522
更新日期:2011-03-01 00:00:00
abstract::The androgen receptor (AR) plays a crucial role in the physiological and pathological functions of androgen. As a transcription factor, the AR modulates androgen activity by regulating the transcription of target genes that are involved in numerous physiological functions and pathological disorders, such as acne vulga...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/187152009789124655
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abstract:BACKGROUND:High-risk human papillomavirus (HR-HPV) persistent infection is the main cause of cervical cancer and its precancerous lesions. A previous study showed that HPV16 and HPV58 infections were the most common infection types in the local region. Some studies also declared that HPV58 E7 variants increased the ris...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520620666201106085227
更新日期:2020-11-05 00:00:00
abstract:METHODS:A novel series of isoxazole (S21-S30) derivatives were designed, synthesized and screened for their anticancer activity against estrogen receptor-positive MCF-7 and negative MDA-MB-435 breast cancer cell lines. The synthesized derivative has the ability to inhibit the growth of the human breast cancer cell line...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520618666171129153655
更新日期:2018-01-01 00:00:00
abstract::In both bacteria and eukaryotes the alkylated, oxidized, and deaminated bases and depurinated lesions are primarily repaired via an endogenous preventive pathway, i.e. base excision repair (BER). Radiation therapy and chemotherapy are two important modes of cancer treatment. Many of those therapeutic agents used in th...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/187152008784220366
更新日期:2008-05-01 00:00:00
abstract::A large group of aminoalkyl and aminoalkanol derivatives of selected dicarboximides were synthesized and characterized by 1HNMR, 13CNMR and ESI MS spectra analysis. The thirty nine new compounds were tested for their cytotoxic properties in human chronic (K562), acute leukemia (HL-60), and cervical cancer cells (HeLa)...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520616666160223114318
更新日期:2016-01-01 00:00:00
abstract::Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality in the world because current treatments, including both surgical and non-surgical ones, cannot effectively cure this disease. Increasing evidence has revealed the importance of cancer stem cells (CSCs) in hepatocarcinogenesis, an...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/187152011796011091
更新日期:2011-07-01 00:00:00
abstract:BACKGROUND:Tumor recurrence and metastasis are still leading causes of cancer mortality worldwide. The influence of traditional treatment strategies against metastatic tumors may still be limited. To search for novel and powerful agents against tumors has become a major research focus. In this study, Artemisinin (ARM),...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520620666200120100252
更新日期:2020-01-01 00:00:00
abstract::The respiratory epithelium expresses the cholinergic system including nicotinic receptors (nAChRs). It was reported that normal human bronchial epithelial cells (BEC), which are the precursor for squamous cell carcinomas, and small airway epithelial cells (SAEC), which are the precursor for adenocarcinomas, have sligh...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/187152007781058587
更新日期:2007-07-01 00:00:00
abstract::The therapeutic potential of targeting p21-Activated Kinases (PAK1 - 6) for the treatment of cancer has recently gained traction in the biotech industry. Many pharmaceutically-viable ATP competitive inhibitors have been through different stages of pre-clinical development with only a single compound evaluated in human...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2016-01-01 00:00:00
abstract:AIM:The aim of this study is to explore the therapeutic potential of S-allylcysteine (SAC) organosulphur compound as potent immune checkpoint inhibitor PD-L1. BACKGROUND:Natural compounds have been showing tremendous anticancerous potential via suppressing the expression of genes involved in development and progressio...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520620666200728121929
更新日期:2020-07-28 00:00:00
abstract::As cancers are one of the most important causes of human morbidity and mortality worldwide, researchers try to discover novel compounds and therapeutic approaches to decrease survival of cancer cells, angiogenesis, proliferation and metastasis. In the last decade, use of special phytochemical compounds and flavonoids ...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520620666200423071759
更新日期:2020-01-01 00:00:00
abstract::As early as the 1920s, the eminent physician and chemist, Otto Warburg, nominated for a second Nobel Prize for his work on fermentation, observed that the core metabolic signature of cancer cells is a high glycolytic flux. Warburg averred that the prime mover of cancer is defective mitochondrial respiration, which dri...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1871520614666140804224637
更新日期:2014-01-01 00:00:00