Double targeting and aptamer-assisted controlled release delivery of epirubicin to cancer cells by aptamers-based dendrimer in vitro and in vivo

Taghdisi, Seyed Mohammad; Danesh, Noor Mohammad; Ramezani, Mohammad; Lavaee, Parirokh; Jalalian, Seyed Hamid; Yazdian-Robati, Rezvan; Abnous, Khalil

doi:10.1016/j.ejpb.2016.03.013

Cited by 119 publications

(40 citation statements)

References 31 publications

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“…The tight complexing structure, like a dandelion achene, would firmly hold the drug while disperse it with a gust of ATP flow. Different from the nucleotide‐based backbone drug vector, this formulation could maintain stable nanostructure without addition of positive‐charged proteins or polymers thus reducing potential cytotoxicity of the drug delivery system . To further fuel the endocytosis efficiency of the nanoparticle, both the l ‐form and the d ‐form of [des‐Arg 10 ]kallidin would be tested as the active targeting ligands.…”

Section: Introductionmentioning

confidence: 99%

ATP/pH Dual Responsive Nanoparticle with d‐[des‐Arg¹⁰]Kallidin Mediated Efficient In Vivo Targeting Drug Delivery

Zhang

Lü

Wang

et al. 2016

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Inflammation has been reported as one significant hallmark of breast cancer in relation to tumor development, metastasis, and invasion. The bradykinin receptor 1 (B1R) is highly expressed on inflammatory breast tumor cells thus providing a promising targeting site for tumor recognition and sufficient receptor mediated endocytosis. In this study, the authors evaluate the targeting efficiency of l-form and d-form [des-Arg ]kallidin both in vitro and in vivo. To further improve the drug delivery efficiency, the authors establish a dandelion like nanoparticle by combining the polymeric drug conjugates and aptamer complex together. The doxorubicin conjugated polymer is complexed with adenosine-5'-triphosphate (ATP) sensitive hybridized aptamer in self-assembly process by intercalating into the double strand scaffolds. The acid labile conjugating bond and ATP sensitive aptamer endow the nanoparticle with dual responsiveness to intracellular milieu, thus triggering a quick drug release in tumor cells. Remarkable therapeutic effects and tuned in vivo pharmacokinetics profiles are shown by the aptamer complexed drug conjugates nanoparticle with B1R active targeting modification. Therefore the strategies of B1R targeting and ATP/pH dual-responsiveness nanoparticle help achieve enhanced drug accumulation within tumor cells and efficient chemotherapy for breast cancer.

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Section: Introductionmentioning

confidence: 99%

ATP/pH Dual Responsive Nanoparticle with d‐[des‐Arg¹⁰]Kallidin Mediated Efficient In Vivo Targeting Drug Delivery

Zhang

Lü

Wang

et al. 2016

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“…An interesting study by Taghdisi et al involved the development of aptamer-based dendrimers with a double targeting strategy (two aptamers: MUC1 and AS1411) and encapsulating epirubicin (Epi), an anthracycline drug, acting against cancer cells in vitro and in vivo ( Figure 4) [25]. Clinical administration of Epi (e.g., to breast and colon cancers) has been limited by nonspecific interactions inducing cardiotoxicity and bone marrow suppression.…”

Section: Dendrimer-aptamer Bioconjugates In Nanomedicinementioning

confidence: 99%

Dendrimer– and polymeric nanoparticle–aptamer bioconjugates as nonviral delivery systems: a new approach in medicine

Mignani

Shi

Ceña

et al. 2020

Drug Discovery Today

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Research Highlights Dendrimer-aptamer conjugates Polymer-aptamer conjugates  Delivery aptamers Cancer Aptamers are RNA or DNA oligonucleotides interacting to form unique 3D target conformations with high affinity and specificity, and are emerging as a powerful class of ligands for therapeutic applications. In addition, dendrimers are well-defined nano-sized symmetric polymeric molecules. In this review, we provide an analysis of the use of dendrimers modified with aptamers as nonviral vectors to specifically target tumor cells. Various anticancer agents have been encapsulated with dendrimers complexing with aptamers, including epirubicin, camptothecin, Bcl-xL short hairpin (sh)RNA, and 5-fluorouracil rhodamine-labeled dextran. Other types of polymeric nanoparticle (NP)-aptamer bioconjugates have also been developed and loaded with Pt(IV) derivatives, to target specific tumor cells. Keywords: dendrimer space; aptamers; polymeric nanoparticles; drug delivery. Teaser: We discuss the development of dendrimer-and polymeric nanoparticle-aptamer bioconjugates as a new approach in medicine Aptamer-based tools for therapeutic monitoring for precision therapy Aptamer comes from the Latin 'aptare' meaning to fit together or join, and from the Greek 'meros' meaning part. A nucleic acid aptamer is a short chain of artificial oligonucleotides of RNA or single-stranded DNA with a variable region of ~40-100 nucleotide bases [1]. Their unique, flexible 3D structure, and their high affinity and specificity with ligand-binding capabilities, are strongly related to their sequence. These important characteristics increase their ability to differentiate between targets. In contrast to antibodies, aptamers can bind to functional domains of their cognate target protein (e.g., substrate binding pockets and allosteric sites) ( Figure 1) [2]. Aptamers are considered to be 'smart ligands' and are often named 'nucleic acid antibodies'. The binding between aptamers and user-defined targets occurs through electrostatic interactions, which result in their versatility. The strong binding affinity and exceptional specificity induces a nano-or pico-molar dissociation constant (Kd). Their targets vary from small ions, such as Zn 2+, and large proteins, such as coagulation factor VIII, to whole cells, viruses, and tissues [3]. J o u r n a l P r e -p r o o f

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“…The Dox–APT–DNA–icosa were much more cytotoxic to MUC1+ cells than were either free DOX or DOX–DNA–icosa . Our group has used a DNA dendrimer (APT‐dendrimer) nanocarrier for MUC1‐targeted delivery of epirubicin (Epi) . Epi, an epimer of DOX, is most active during the S phase of the cell cycle.…”

Section: The Muc1 Aptamer In Targeted Drug Deliverymentioning

confidence: 99%

“…Tumor volumes after treatment with the double targeting NPs were significantly reduced when compared with the other treatment groups. Interestingly, the use of this dual targeting strategy significantly increased the targeting efficiency of MUC1 through renal clearance. Consequently, this aptamer and drug complex may be ineffective in vivo …”

Section: The Muc1 Aptamer In Targeted Drug Deliverymentioning

confidence: 99%

Anti‐MUC1 aptamer: A potential opportunity for cancer treatment

Nabavinia

Gholoobi

Charbgoo

et al. 2017

Medicinal Research Reviews

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Double targeting and aptamer-assisted controlled release delivery of epirubicin to cancer cells by aptamers-based dendrimer in vitro and in vivo

Cited by 119 publications

References 31 publications

ATP/pH Dual Responsive Nanoparticle with d‐[des‐Arg¹⁰]Kallidin Mediated Efficient In Vivo Targeting Drug Delivery

ATP/pH Dual Responsive Nanoparticle with d‐[des‐Arg¹⁰]Kallidin Mediated Efficient In Vivo Targeting Drug Delivery

Dendrimer– and polymeric nanoparticle–aptamer bioconjugates as nonviral delivery systems: a new approach in medicine

Anti‐MUC1 aptamer: A potential opportunity for cancer treatment

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Double targeting and aptamer-assisted controlled release delivery of epirubicin to cancer cells by aptamers-based dendrimer in vitro and in vivo

Cited by 119 publications

References 31 publications

ATP/pH Dual Responsive Nanoparticle with d‐[des‐Arg10]Kallidin Mediated Efficient In Vivo Targeting Drug Delivery

ATP/pH Dual Responsive Nanoparticle with d‐[des‐Arg10]Kallidin Mediated Efficient In Vivo Targeting Drug Delivery

Dendrimer– and polymeric nanoparticle–aptamer bioconjugates as nonviral delivery systems: a new approach in medicine

Anti‐MUC1 aptamer: A potential opportunity for cancer treatment

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ATP/pH Dual Responsive Nanoparticle with d‐[des‐Arg¹⁰]Kallidin Mediated Efficient In Vivo Targeting Drug Delivery

ATP/pH Dual Responsive Nanoparticle with d‐[des‐Arg¹⁰]Kallidin Mediated Efficient In Vivo Targeting Drug Delivery