An iTEP-salinomycin nanoparticle that specifically and effectively inhibits metastases of 4T1 orthotopic breast tumors

Zhao, Peng; Xia, Guiquan; Dong, Shuyun; Jiang, Zhaong Xing; Chen, Mingnan

doi:10.1016/j.biomaterials.2016.03.032

Cited by 31 publications

(29 citation statements)

References 36 publications

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“…We incorporated versatile application for drug delivery into the innate design of iTEPs. They have been used to deliver a small molecule drug as a good inert carrier [50,51] . They have also been used to deliver CTL vaccine, and the vaccine potency was exaggerated by loading with immunogenic adjuvant, in this case the H 100 peptide, to trigger a desired immune response.…”

Section: Discussionmentioning

confidence: 99%

Engineering of a self-adjuvanted iTEP-delivered CTL vaccine

Dong

Wang

et al. 2017

Acta Pharmacol Sin

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Cytotoxic T lymphocyte (CTL) epitope peptide-based vaccines are widely used in cancer and infectious disease therapy. We previously generated an immune-tolerant elastin-like polypeptides (iTEPs)-based carrier to deliver a peptide CTL vaccine and enhance the efficiency of the vaccine. To further optimize the vaccine carrier, we intended to potentiate its function by designing an iTEP-based carrier that was able to deliver adjuvant and a vaccine epitope as one molecule. Thus, we fused a 9-mer H, a peptide derived from the high-mobility group box 1 protein (HMGB1) that could induce activation of dendritic cells (DCs), with an iTEP polymer to generate a new iTEP polymer named H-iTEP. The H-iTEP still kept the feature of reversible phase transition of iTEPs and should be able to be used as a polymer carrier to deliver peptide vaccines. The expression levels of CD80/CD86 on DCs were assessed using flow cytometry. The iTEP fusion-stimulated IL-6 secretion by DCs was measured with ELISA. Activation of antigen-specific CD8 T cells induced by iTEP fusions was examined through a B3Z hybridoma cell activation assay. In vivo CTL activation promoted by iTEP fusions was detected by an IFN-γ-based ELISPOT assay. The iTEP fused with H could induce maturation of DCs in vitro as evidenced by increased CD80 and CD86 expression. The iTEP fusion also promoted activation of DCs by increasing secretion of a proinflammatory cytokine IL-6. The N-terminus or C-terminus fusion of H to iTEP had a similar effect and a reduced form of cysteine in iTEP fusions was required for DC stimulation. iTEP fusions potentiated a co-administrated CTL vaccine by increasing an antigen-specific CTL response in vitro and in vivo. When the H-iTEP was fused to a CTL epitope to generate a one-molecule vaccine, this self-adjuvanted vaccine elicited a stronger antigen-specific CTL response than a vaccine adjuvanted by Incomplete Freund's Adjuvant. Thus, we have successfully generated a functional, one-molecule iTEP-based self-adjuvanted vaccine.

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Section: Discussionmentioning

confidence: 99%

Engineering of a self-adjuvanted iTEP-delivered CTL vaccine

Dong

Wang

et al. 2017

Acta Pharmacol Sin

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“…And then 0.1 mL of cells was inoculated into mice at the armpit of right forelimb to establish the model of mouse mammary carcinoma. The largest diameter ( L ) and smallest diameter ( W ) of each tumor were monitored after the inoculation to calculate the tumor volume

Tumor volume = \frac{L \times W^{2}}{2}

…”

Section: Methodsmentioning

confidence: 99%

A Versatile Prodrug Strategy to In Situ Encapsulate Drugs in MOF Nanocarriers: A Case of Cytarabine‐IR820 Prodrug Encapsulated ZIF‐8 toward Chemo‐Photothermal Therapy

Zhang

Liu

et al. 2018

Adv Funct Materials

191

147

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Zeolitic imidazolate framework-8 (ZIF-8) is an attractive metal organic framework (MOF) in drug delivery. Strong interaction between drugs and ZIF-8 is essential for high drug loadings through in situ construction of MOFs. However, only limited drugs with unique functional groups (COOH, SO 3 H, et al.) can interact with ZIF-8 and be encapsulated satisfactorily so far. Drugs without these functional groups are difficult to be loaded due to the lack of strong interaction. Herein a versatile prodrug strategy is proposed to solve the problems encountered by MOFs. Cytarabine (Ara) is chosen as a model drug since it cannot be loaded in ZIF-8 satisfactorily by itself. New indocyanine green (IR820) is utilized to bond with Ara for the formation of prodrug (Ara-IR820) and endows the prodrug with fluorescence imagingguided chemo-photothermal therapy, in which sulfonic groups strengthen the interaction between prodrug and ZIF-8. This prodrug loaded ZIF-8 is further functionalized with hyaluronic acid (HA) to result in active-targeting HA/ Ara-IR820@ZIF-8 nanoparticles. The in vitro and in vivo results demonstrate its excellent visual cancer therapy with tumor-targeted and pH-responsive release behavior. This design offers a new concept to solve the drug loading problem of MOFs, exhibiting a flexible strategy to expand the biomedical applications of MOFs.

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“…Salinomycin was encapsulated into amphiphilic Smo Inhibitor [53] iTEP À Salinomycin conjugates. The nanoconjugates of salinomycin significantly reduced the tumour growth in 4T1-orthotopic breast cancer model [42,43].…”

Section: Nanocarriers For Silencing Wnt/b-catenin Pathwaymentioning

confidence: 97%

Nanocarrier based approaches for targeting breast cancer stem cells

Pindiprolu

Chintamaneni

Karri

2017

Artificial Cells, Nanomedicine, and Biotechnology

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Breast cancer stem cells (BCSCs) are heterogeneous subpopulation of tumour initiating cells within breast tumours. They are spared even after chemotherapy and responsible for tumour relapse. Targeting BCSCs is, therefore, necessary to achieve radical cure in breast cancer. Despite the availability of agents targeting BCSCs, their clinical application is limited due to their off-target effects and bioavailability issues. Nanotechnology based drug carriers (nanocarriers) offer various advantages to deliver anti-BCSCs agents specifically to their target sites by overcoming their bioavailability issues. In this review, we describe various strategies for targeting BCSCs using nanocarriers.

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An iTEP-salinomycin nanoparticle that specifically and effectively inhibits metastases of 4T1 orthotopic breast tumors

Cited by 31 publications

References 36 publications

Engineering of a self-adjuvanted iTEP-delivered CTL vaccine

Engineering of a self-adjuvanted iTEP-delivered CTL vaccine

A Versatile Prodrug Strategy to In Situ Encapsulate Drugs in MOF Nanocarriers: A Case of Cytarabine‐IR820 Prodrug Encapsulated ZIF‐8 toward Chemo‐Photothermal Therapy

Nanocarrier based approaches for targeting breast cancer stem cells

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