DNA–affibody nanoparticle delivery system for cisplatin-based breast cancer chemotherapy

Zhang, Chao; Zhang, Hong Lei; Han, Meng Nan; Yang, Xue Li; Pei, Chao Hong; Xu, Zhi Dong; Du, Jie; Wei, Li; Chen, Shengxi

doi:10.1039/c8ra08735k

Cited by 17 publications

(14 citation statements)

References 29 publications

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“…[146] Using the same affibody-TDN carrier for cisplatin delivery, a 1.6-fold increase in growth inhibition of BT474 cells was obtained. [84] After 72 h incubation, 82.9% of cell growth was inhibited by 33.3 × 10 -6 m cisplatin, whereas treatment with the nanoparticles resulted in 94.6% inhibition. [84] The effect was more pronounced in cells that highly overexpress HER2.…”

Section: Antibodies and Antibody-derived Proteinsmentioning

confidence: 97%

“…[84] After 72 h incubation, 82.9% of cell growth was inhibited by 33.3 × 10 -6 m cisplatin, whereas treatment with the nanoparticles resulted in 94.6% inhibition. [84] The effect was more pronounced in cells that highly overexpress HER2. [84,146] A HER2 affibody was also used by Zhang et al [147] to deliver the antitumor nucleoside analog 5-fluorodeoxyuridine (FUdR).…”

Section: Antibodies and Antibody-derived Proteinsmentioning

confidence: 97%

“…[84] The effect was more pronounced in cells that highly overexpress HER2. [84,146] A HER2 affibody was also used by Zhang et al [147] to deliver the antitumor nucleoside analog 5-fluorodeoxyuridine (FUdR). Polymeric FUdR molecules (consisting of ten FUdRs) were covalently linked to the 5' end of four DNA strands which self-assemble into the TDN.…”

Section: Antibodies and Antibody-derived Proteinsmentioning

confidence: 99%

“…[83] DNs have also been combined with the platinum-based drugs cisplatin and 56MESS. [84][85][86] The effectiveness of cisplatin compared to its Pt(IV) prodrug which was covalently linked to three differently shaped DNs (constructed with the brick method) was observed in cisplatin-resistant cancer cells (A549cisR) and in non-resistant lung cancer cells (A549). [87] The results showed that the DNs could remarkably enhance the cellular internalization of platinum drugs, and thus, increase the anticancer activity for these resistant cell lines.…”

Section: Cargo Molecules For Drug Deliverymentioning

confidence: 99%

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Prospective Cancer Therapies Using Stimuli‐Responsive DNA Nanostructures

Seitz

Ahmed

Nurmi

et al. 2021

Macromolecular Bioscience

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Nanostructures based on DNA self-assembly present an innovative way to address the increasing need for target-specific delivery of therapeutic molecules. Currently, most of the chemotherapeutics being used in clinical practice have undesired and exceedingly high off-target toxicity. This is a challenge in particular for small molecules, and hence, developing robust and effective methods to lower these side effects and enhance the antitumor activity is of paramount importance. Prospectively, these issues could be tackled with the help of DNA nanotechnology, which provides a route for the fabrication of custom, biocompatible, and multimodal structures, which can, to some extent, resist nuclease degradation and survive in the cellular environment. Similar to widely employed liposomal products, the DNA nanostructures (DNs) are loaded with selected drugs, and then by employing a specific stimulus, the payload can be released at its target region. This review explores several strategies and triggers to achieve targeted delivery of DNs. Notably, different modalities are explained through which DNs can interact with their respective targets as well as how structural changes triggered by external stimuli can be used to achieve the display or release of the cargo. Furthermore, the prospects and challenges of this technology are highlighted.

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Section: Antibodies and Antibody-derived Proteinsmentioning

confidence: 97%

Section: Antibodies and Antibody-derived Proteinsmentioning

confidence: 97%

Section: Antibodies and Antibody-derived Proteinsmentioning

confidence: 99%

Section: Cargo Molecules For Drug Deliverymentioning

confidence: 99%

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Prospective Cancer Therapies Using Stimuli‐Responsive DNA Nanostructures

Seitz

Ahmed

Nurmi

et al. 2021

Macromolecular Bioscience

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“…Then, this nanoparticle was employed for transporting doxorubicin and cisplatin to specific cancer cells through non-covalent bonding, respectively, to enhance the targeting of drug treatment. 23,24 However, their main issues are the difficulty in accurately controlling drug loading and the leak of chemotherapy drugs during in vivo transport. 25 These are the main obstructions in the development and clinical application of this kind of nanodrugs.…”

Section: Introductionmentioning

confidence: 99%

<p>Enhancing Antitumor Efficacy of Nucleoside Analog 5-Fluorodeoxyuridine on HER2-Overexpressing Breast Cancer by Affibody-Engineered DNA Nanoparticle</p>

Zhang¹,

Han²,

Zhang³

et al. 2020

IJN

Self Cite

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Background: Chemotherapy, as an adjuvant treatment strategy for HER2-positive breast cancer, can effectively improve clinical symptoms and overcome the drug resistance of therapeutic monoclonal antibodies. Nucleoside analogues are a class of traditional chemotherapeutic drugs that are widely applied in adjuvant therapy. However, there are many critical issues that limit their clinical efficiency, including poor selectivity and stability, severe side effects and suboptimal therapeutic efficacy. Hence, this work aims to develop a new DNA nanocarrier for targeted drug delivery to solve the above problems. Methods: Four 41-mer DNA strands were synthesized and 10 FUdR molecules were attached to 5ʹ end of each DNA strand by DNA solid-phase synthesis. An affibody molecule was connected to the end of polymeric FUdR through a linker in one of the four strands. The affibody-FUdR-tetrahedral DNA nanostructures (affi-F/TDNs) were self-assembled through four DNA strands, in which one vertex was connected to an affibody at the end of a polymeric FUdR tail and three vertices were only polymeric FUdR tails. In vitro cellular uptake of affi-F/TDNs was examined visually with confocal fluorescence microscopy and flow cytometry, and the cytotoxicity of affi-F/TDNs against cancer cells was investigated with MTT assay. Cell apoptosis was detected by Annexin V-FITC/PI double staining method. Using NOD/SCID (Mus Musculus) mice model, the targeted killing efficacy of affi-F/TDNs was also evaluated. Results: The drug-loading of FUdR in affi-TDNs was 19.6% in mole ratio. The in vitro results showed that affi-F/TDNs had high selectivity and inhibition (81.2%) for breast cancer BT474 cells overexpressing HER2 and low toxicity in MCF-7 cells with low HER2 expression. During the in vivo application, affi-F/TDNs displayed good stability in the blood circulation, achieved specific accumulation in tumor region and the best antitumor efficacy (inhibition ratio of 58.1%), and showed excellent biocompatibility. Conclusions: The affibody-DNA tetrahedrons, as a simple and effective active targeting delivery nanocarrier, provided a new avenue for the transport of nucleoside antitumor drugs.

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Affibody‐Conjugated RALA Polymers Delivering Oligomeric 5‐Fluorodeoxyuridine for Targeted Therapy of HER2 Overexpressing Gastric Cancer

Zhang

Yin

Zhang

et al. 2020

Macromolecular Bioscience

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Affibody‐conjugated RALA (affi‐RA) are designed for delivering oligomeric 5‐fluorodeoxyuridine (FUdR, metabolite of 5‐FU) strand to raise the selectivity of 5‐fluorouracil (5‐FU), decrease its toxicity and improve its suboptimal therapeutic efficacy. The nanodrugs, FUdR@affi‐RA, are spontaneously assembled by electrostatic interaction between positively charged affi‐RA and negatively charged FUdR15‐strands (15 consecutive FUdR). FUdR@affi‐RA exhibits excellent stability under simulated physiological conditions. Compared with free FUdR, FUdR@affi‐RA shows excellent targeting and higher cytotoxicity in human epidermal growth factor receptor 2 (HER2) overexpressing gastric cancer N87 cells. Moreover, the anticancer mechanism studies reveal that FUdR@affi‐RA enhances the expression and activity of apoptosis‐associated proteins in the Bcl‐2/Bax‐caspase 8,9‐caspase 3 apoptotic pathway induced by FUdR. This study indicates that the fusion vector, affi‐RA, presents a promising delivery system platform for nucleoside analogue drugs and provides a new strategy for the development of therapeutics of cancer treatment.

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DNA–affibody nanoparticle delivery system for cisplatin-based breast cancer chemotherapy

Abstract: The novel nano-drug cisplatin-DNA tetrahedron-affibody has high specificity, high efficacy, and low toxicity for the treatment of HER2-overexpressing breast cancers.

Cited by 17 publications

References 29 publications

Prospective Cancer Therapies Using Stimuli‐Responsive DNA Nanostructures

Prospective Cancer Therapies Using Stimuli‐Responsive DNA Nanostructures

<p>Enhancing Antitumor Efficacy of Nucleoside Analog 5-Fluorodeoxyuridine on HER2-Overexpressing Breast Cancer by Affibody-Engineered DNA Nanoparticle</p>

Affibody‐Conjugated RALA Polymers Delivering Oligomeric 5‐Fluorodeoxyuridine for Targeted Therapy of HER2 Overexpressing Gastric Cancer

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