Development of a novel near-infrared fluorescent theranostic combretastain A-4 analogue, YK-5-252, to target triple negative breast cancer

2017 ◽  
Vol 25 (7) ◽  
pp. 2226-2233 ◽  
Author(s):  
Yali Kong ◽  
Jacqueline Smith ◽  
Kongwen Li ◽  
Jake Cui ◽  
John Han ◽  
...  
Nano Research ◽  
2021 ◽  
Author(s):  
Alessia Felici ◽  
Daniele Di Mascolo ◽  
Miguel Ferreira ◽  
Simone Lauciello ◽  
Luca Bono ◽  
...  

AbstractTaxane efficacy in triple negative breast cancer (TNBC) is limited by insufficient tumor accumulation and severe off-target effects. Nanomedicines offer a unique opportunity to enhance the anti-cancer potency of this drug. Here, 1,000 nm × 400 nm discoidal polymeric nanoconstructs (DPN) encapsulating docetaxel (DTXL) and the near infrared compound lipid-Cy5 were engineered. DPN were obtained by filling multiple times cylindrical wells in a poly(vinyl alcohol) template with a polymer mixture comprising poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) diacrylate (PEG-DA) chains together with therapeutic and imaging agents. The resulting “multi-passage” DPN exhibited higher DTXL loading, lipid-Cy5 stability, and stiffness as compared to the conventional “single-passage” approach. Confocal microscopy confirmed that DTXL-DPN were not taken up by MDA-MB-231 cells but would rather sit next to the cell membrane and slowly release DTXL thereof. Empty DPN had no toxicity on TNBC cells, whereas DTXL-DPN presented a cytotoxic potential comparable to free DTXL (IC50 = 2.6 nM ± 1.0 nM vs. 7.0 nM ± 1.09 nM at 72 h). In orthotopic murine models, DPN accumulated in TNBC more efficiently than free-DTXL. With only 2 mg/kg DTXL, intravenously administered every 2 days for a total of 13 treatments, DTXL-DPN induced tumor regression and were associated to an overall 80% survival rate as opposed to a 30% survival rate for free-DTXL, at 120 days. All untreated mice succumbed before 90 days. Collectively, this data demonstrates that vascular confined multi-passage DPN, biomimicking the behavior of circulating platelets, can efficiently deliver chemotherapeutic molecules to malignant tissues and effectively treat orthotopic TNBC at minimal taxane doses.


Author(s):  
Wei Xie ◽  
Huijie Zhao ◽  
Fengxian Wang ◽  
Yiyun Wang ◽  
Yuan He ◽  
...  

Abstract Background Anti-angiogenic therapy has been widely applied to the clinical treatment of malignant tumors. However, the efficacy of such treatments has been called into question, especially in triple-negative breast cancer (TNBC). Bevacizumab, the first anti-angiogenic agent approved by FDA, actually increases invasive and metastatic properties of TNBC cells, resulting from the activation of Wnt/β-catenin signaling in response to hypoxia. As a critical receptor of Wnt/β-catenin signaling, Frizzled-7 (Fzd7) is aberrantly expressed in TNBC, indicating Fzd7 a potential target for developing drugs to be combined with anti-angiogenic agents. Methods Hybridoma technique and antibody humanization technique were utilized to generate a Fzd7-targeting antibody (SHH002-hu1). Biolayer interferometry (BLI) assay and near infrared (NIR) imaging were conducted to detect the affinity and targeting ability of SHH002-hu1. Next, whether SHH002-hu1 could suppress the invasion and migration of TNBC cells induced by Bevacizumab were validated, and the underlying molecular mechanisms were elucidated by luciferase reporter and western blot assays. The nude-mice transplanted TNBC models were established to assess the anti-TNBC activities of SHH002-hu1 when combined with Bevacizumab. Then, the effects on putative TNBC stem-like cells and Wnt/β-catenin signaling were evaluated by immunofluorescence (IF). Further, the tumor-initiating and self-renew capacity of TNBC cells were studied by secondary nude mouse xenograft model and sphere formation assay. In addition, the effects of SHH002-hu1 on the adaptation of TNBC cells to hypoxia were evaluated by the detection of vasculogenic mimicry (VM) and hypoxia-inducible factor-1α (HIF-1α) transcriptional activity. Results The novel humanized antibody targeting Fzd7 (SHH002-hu1) exhibited extremely high affinity with Fzd7, and specifically targeted to Fzd7+ cells and tumor tissues. SHH002-hu1 repressed invasion, migration and epithelial-mesenchymal cell transformation (EMT) of TNBC cells induced by Bevacizumab through abating Wnt/β-catenin signaling. SHH002-hu1 significantly enhanced the capacity of Bevacizumab to inhibit the growth of TNBC via reducing the subpopulation of putative TNBC stem-like cells, further attenuating Bevacizumab-enhanced tumor-initiating and self-renew capacity of TNBC cells. Moreover, SHH002-hu1 effectively restrained the adaptation of TNBC cells to hypoxia via disrupting Wnt/β-catenin signaling. Conclusion SHH002-hu1 significantly enhances the anti-TNBC capacity of Bevacizumab, and shows the potential of preventing TNBC recurrence, suggesting SHH002-hu1 a good candidate for the synergistic therapy together with Bevacizumab.


Oncotarget ◽  
2017 ◽  
Vol 8 (49) ◽  
pp. 86566-86575 ◽  
Author(s):  
Meihua Zhang ◽  
Hoe Suk Kim ◽  
Tiefeng Jin ◽  
Jisu Woo ◽  
Yin Ji Piao ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Ke Li ◽  
Ruyue Li ◽  
Baona Zhou ◽  
Jing Chen ◽  
Kai Lan ◽  
...  

Triple-negative breast cancer (TNBC) has inadequate treatment approaches and a poor prognosis. It is urgent to develop new treatment approaches for TNBC. The combination of photothermal therapy (PTT) and chemotherapy is a very effective potential therapy for TNBC. However, asynchronous accumulation, unclear efficacy, and toxic side effects hinder the further promotion of this method. Therefore, we designed and constructed a new type of nanocarriers, the cascade release near-infrared imaging (NIFI) & thermal-chemo combination nanoparticles (CNC NPs), that can release drugs through the cascade of ultrasound triggering and pH responding to achieve the synchronous tumor accumulation, monitoring and synergistic treatment of two functional molecules. The key material of CNC NPs is the polydopamine (PDA), which, through self-assembling, forms a rigid shell that contains doxorubicin (DOX) and NIF fluorescent dye IR780 on the surface of the perfluorohexane (PFH) microbubbles. The results show that CNC NPs have a hollow core-shell structure with an average particle size of 97.3 ± 27.2 nm and have exceptional colloidal stability and photothermal conversion efficiency. The NPs can effectively perform cascade drug release through ultrasound triggering and pH responding. CNC NPs have good in vivo biological safety and excellent fluorescence imaging, drug delivery, and therapeutic abilities in the TNBC models. These results provide an experimental basis for the development of new clinical treatment methods for TNBC.


PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0136829 ◽  
Author(s):  
Tadanobu Nagaya ◽  
Kazuhide Sato ◽  
Toshiko Harada ◽  
Yuko Nakamura ◽  
Peter L. Choyke ◽  
...  

Nanomedicine ◽  
2020 ◽  
Vol 15 (6) ◽  
pp. 581-601 ◽  
Author(s):  
Anuradha Gadeval ◽  
Rahul Maheshwari ◽  
Nidhi Raval ◽  
Dnyaneshwar Kalyane ◽  
Kiran Kalia ◽  
...  

Aim: Green graphene oxide (GO) nanoplates, which are reduced and stabilized by quercetin and guided by folate receptors (quercetin reduced and loaded GO nanoparticles-folic acid [FA]), were developed to mediate combined photo-chemo-thermal therapy of triple-negative breast cancer. Materials & methods: Modified Hummers method was used for the synthesis of GO followed by its reduction using quercetin, FA was then conjugated as a targeting ligand. A cytotoxicity assay, apoptosis assay and cellular uptake assay were performed in vitro in MDA-MB-231 cell line with and without irradiation of a near-infrared 808 nm laser. Results & conclusion: Quercetin reduced and loaded GO nanoparticles-FA showed significantly high cellular uptake (p < 0.001) and cytotoxic effects in MDA-MB-231 cells, which was even more prominent under the situation of near-infrared 808 nm laser irradiation, making it a potential option for treating triple-negative breast cancer.


Nanoscale ◽  
2015 ◽  
Vol 7 (36) ◽  
pp. 14854-14864 ◽  
Author(s):  
Bing Feng ◽  
Zhiai Xu ◽  
Fangyuan Zhou ◽  
Haijun Yu ◽  
Qianqian Sun ◽  
...  

Gold nanorods with cisplatin–polypeptide wrapping were developed for combinational photothermal therapy and chemotherapy of triple negative breast cancer.


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