scholarly journals Functionalized Organic–Inorganic Liposome Nanocomposites for the Effective Photo-Thermal Therapy of Breast Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Haibin Liu ◽  
Feng Zhuang ◽  
Chengjian Zhang ◽  
Wanzhao Ai ◽  
Wei Liu ◽  
...  

Organic–inorganic nanocomposites for photothermal therapy of cancers emerged as a promising strategy against malignant tumors. However, it is still a big challenge to develop a nanocomposite system that can maximize the synergistic photo-thermal therapy effect as well as preserve high stability for simultaneous delivery of the chemotherapeutic drugs and photo-thermal agents. Here, we have exploited an organic liposome containing inorganic core for co-loading the aggregates of bovine serum albumin (BSA), indocyanine green (ICG), and doxorubicin (DOX), abbreviated as BID-liposomal nanocomposites. The three kinds of substances were aggregated in the core of liposomal nanocomposites through hydrophobic and electrostatic interactions. In vitro characterization shows that BID-liposomal nanocomposites were spherical nanoparticles with size of 30–50 nm and good storage stability. Moreover, BID-Liposomal nanocomposites illustrate the strongest cytotoxicity among all the formulations against murine 4T1 tumor cells. In breast cancer-bearing mouse models, BID liposomes lead to significant improvements in tumor inhibition effects with no obvious toxicity. Therefore, the BID-liposomal nanoparticle is believed to be a promising strategy for chemo-photo-thermal therapy against cancers.

2019 ◽  
Vol 33 (9) ◽  
pp. 1202-1213 ◽  
Author(s):  
Hao Li ◽  
Wei Zhang ◽  
Li Ding ◽  
Xing-Wang Li ◽  
Yang Wu ◽  
...  

To realize the photothermal therapy ability of Prussian blue-modified ferritin nanoparticles (PB-Ft NPs) and its synergistic effect with chemotherapy, PB-Ft NPs were synthesized by a simple surface double decomposition reaction. Mean sizes of ferritin and PB-Ft NPs were 10.4 nm and 12.6 nm, respectively. The obtained PB-Ft NPs were verified to have both the photothermal conversion ability of Prussian blue and the morphology of ferritin. The in vitro and in vivo photothermal therapy results confirm PB-Ft NPs can successfully inhibit the growth of murine breast cancer cell line (4T1) without any obvious side effect. Moreover, taking use of the peroxidase-like activity of PB-Ft NPs, the photothermal therapy effect of PB-Ft NPs effectively improved the curative effect of gemcitabine (GEM) via enhancing reactive oxygen species production. The obtained PB-Ft NPs can be served as a useful and safe photothermal therapy agent in breast cancer. Moreover, PB-Ft NPs-assisted photothermal therapy can be applied as an adjunctive therapy with various established cancer treatments such as chemotherapy.


2021 ◽  
Author(s):  
yujuan Kang ◽  
Lin Wan ◽  
Qin Wang ◽  
Yanling Yin ◽  
Jiena Liu ◽  
...  

Abstract Background: Long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) plays a positive role in the progression of human malignant tumors. However, the molecular mechanism of SNHG1 remains elusive in breast cancer. Results: LncRNA SNHG1 was upregulated and had a positive relationship with poor prognosis according to bioinformatics analysis. Silencing SNHG1 inhibited tumorigenesis in breast cancer both in vitro and in vivo. Mechanistically, SNHG1 functioned as a ceRNA to promote TERT expression by sponging miR-18b-5p. Moreover, miR-18b-5p acted as a tumor repressor in breast cancer. Finally, E2F1, a transcription factor, enhanced SNHG1 transcription.Conclusions: Our results provide a comprehensive understanding of the oncogenic mechanism of lncRNA SNHG1 in breast cancer. Importantly, we identified a novel E2F1–SNHG1–miR-18b-5p–TERT axis, which may be a potential therapeutic target for breast cancer.


2017 ◽  
Vol 77 (08) ◽  
pp. 861-869 ◽  
Author(s):  
Angrit Stachs ◽  
Steffi Hartmann ◽  
Bernd Gerber

AbstractBecause of the efficacy of systemic therapies, neoplasias which occur in pediatric and adolescent patients and in young adults have high cure rates. This means that fulfilling their wish to have children has become a more pressing concern, particularly among young women with malignant tumors. Premature ovarian failure is also a not insignificant problem as it has a lasting detrimental effect on quality of life. Every oncology patient who may potentially wish to have children should be informed about their options for preserving fertility prior to starting treatment. The rates of patient who received detailed briefing on this point remain low. This review presents the effects of different chemotherapeutic drugs on gonadal function together with an overview of currently valid recommendations on fertility preservation. Risk groups are defined and the specific approaches for malignancies of various organ systems are described. Cryopreservation of oocytes, fertilized embryos and ovarian tissue are fertility-preserving options for girls/young women. The data on the benefits of administering GnRH analogs for ovarian protection prior to starting chemotherapy are not clear. In postpubertal boys or male cancer patients, the standard approach is to cryopreserve sperm before starting therapy. The cryopreservation of testicular tissue is possible for prepubertal boys, however in-vitro sperm maturation is still in its experimental stages. This review also presents existing drug options for the preservation of ovarian function in oncology patients prior to chemotherapy, particularly for patients with (hormone-sensitive) breast cancer, and looks at the special issues of fertility-preserving surgery and radiation therapy in patients with gynecologic malignancies.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yi Li ◽  
Kexin Wang ◽  
Yupeng Chen ◽  
Jieqi Cai ◽  
Xuemei Qin ◽  
...  

Breast cancer (BC) is one of the most common malignant tumors among women worldwide and can be treated using various methods; however, side effects of these treatments cannot be ignored. Increasing evidence indicates that compound kushen injection (CKI) can be used to treat BC. However, traditional Chinese medicine (TCM) is characterized by “multi-components” and “multi-targets”, which make it challenging to clarify the potential therapeutic mechanisms of CKI on BC. Herein, we designed a novel system pharmacology strategy using differentially expressed gene analysis, pharmacokinetics synthesis screening, target identification, network analysis, and docking validation to construct the synergy contribution degree (SCD) and therapeutic response index (TRI) model to capture the critical components responding to synergistic mechanisms of CKI in BC. Through our designed mathematical models, we defined 24 components as a high contribution group of synergistic components (HCGSC) from 113 potentially active components of CKI based on ADME parameters. Pathway enrichment analysis of HCGSC targets indicated that Rhizoma Heterosmilacis and Radix Sophorae Flavescentis could synergistically target the PI3K-Akt signaling pathway and the cAMP signaling pathway to treat BC. Additionally, TRI analysis showed that the average affinity of HCGSC and targets involved in the key pathways reached -6.47 kcal/mmol, while in vitro experiments proved that two of the three high TRI-scored components in the HCGSC showed significant inhibitory effects on breast cancer cell proliferation and migration. These results demonstrate the accuracy and reliability of the proposed strategy.


2018 ◽  
Vol 8 (5-s) ◽  
pp. 139-142 ◽  
Author(s):  
Muthu Dhandapani ◽  
Babu Balakrishnan ◽  
Ganesan Sivamani

Dysfunctions of Wnt, Hedgehog and Notch pathways are evident in multiple tumor types and malignancies. A number of studies have suggested that dysregulation of Wnt/β-catenin signaling occurs in human breast cancer. Specifically, inhibition of Wnt/ β-catenin pathway is implicated in arresting of cancer stem cells (CSCs), a small subset of cancer cells capable of self-renewal and differentiation into heterogeneous tumor cells. Here, we investigated tumor initiating property of breast cancer stem cell in-vitro with XAV-939 an inhibitor of Wnt/β-catenin signaling pathway. Targeting Wnt/β-catenin signaling with this inhibitor represents a promising strategy to suppress metastasis. Keywords: Cancer Stem Cell, 3D Mammosphere, Wnt/β-catenin, metastasis, CD44+/CD24


2020 ◽  
Author(s):  
Yan Shen ◽  
Yuan Ding ◽  
Jiasheng Tu ◽  
Pengcheng Xu ◽  
Wenqian Yang ◽  
...  

Abstract BackgroundAlthough many treatments are available for breast cancer, poor tumor targeting limits the effectiveness of most approaches and a monotherapy will yield satisfactory results difficultly. Furthermore, the lack of accurate diagnostic and tumor monitoring methods also limit the benefits of treatment. This study aimed to design a nanocarrier based on porous gold nanoshell (PGNSs) co-decorated with methoxy polyethylene glycol (mPEG) and trastuzumab (Herceptin®, HER) which can specifically bind to human epidermal receptor-2 (Her-2) over-expressed breast cancer cells and was incorporated with a derivative of the microtubule-targeting drug maytansine (DM1). PGNSs were prepared and then covered by the mPEG, DM1 and HER via the electrostatic interactions and Au-S bonds. The cytotoxicity of DM1-mPEG/HER-PGNSs on SK-BR-3 and MCF-7 cancer cells was evaluated in terms of cell viability and apoptosis analysis. The selective cancer cell uptake and accumulation were studied via ICP-MS and fluorescence imaging in vitro and in vivo. The multimodal imaging and synergistic chemo-photothermal therapeutic efficacy was investigated in breast cancer tumor-bearing mice. Then the molecular mechanism of the nanoparticles in anti-tumor applications were also elucidated.ResultThe as-prepared DM1-mPEG/HER-PGNSs with a size of 78.6 nm displayed excellent colloidal stability, photothermal conversion ability, and redox-sensitive drug release. These DM1-mPEG/HER-PGNSs exhibited selectively uptake by cancer cells in vitro and accumulation to tumor sites in vivo. Moreover, the DM1-mPEG/HER-PGNSs showed enhanced multimodal computed tomography (CT), photoacoustic (PA) and photothermal (PT) imaging and chemo-thermal combination therapy. The therapeutic mechanism involved the induction of tumor cell apoptosis via the activation of tubulin, caspase-3 and the HSP70 pathway. Meanwhile, the suppression of M2 macrophages and anti-metastatic functions were observed.ConclusionThese DM1-mPEG/HER-PGNSs would display nanodart-like targeting CT/PA/PT imaging in vivo and powerful tumor inhibition mediated by chemo-thermal combination therapy suggest that these unique gold nanocarriers are potential theranostic nanoagents that can serve both as a probe for enhanced multimodal imaging and as a novel targeted antitumor drug delivery system to achieve precision nanomedicine for cancer.


2021 ◽  
Vol 19 ◽  
Author(s):  
Haijun Shen ◽  
Qianqian Gao ◽  
Tingting Liu ◽  
Haoran Wang ◽  
Ran Zhang ◽  
...  

Background:: The combination of photothermal therapy (PTT) and chemotherapy has proven to be a promising strategy for cancer treatment. Various nanomaterials have shown great potential in combination therapy, including gold, graphene oxide, iron oxide, and other nanoparticles. However, their undefinable toxicity in vivo greatly slowed down their development for clinical applications. Objective: The present work aimed to develop a multifunctional nanoparticle for chemo-photothermal therapy composed of acknowledged biocompatible materials. Methods: A novel biocompatible nanoparticle (HIT-NPs) was self-assembled through the intrinsic interaction between D-α-tocopherol Succinate (TOS), human serum albumin (HSA) and indocyanine green (ICG). Doxorubicin (DOX) was then loaded due to the ion pairing between DOX and TOS. The feasibility of combined chemo-photothermal therapy induced by DOX-loaded HIT-NPs was carefully evaluated. Results: In vitro, HIT-NPs showed no cytotoxicity on human normal liver cells (HL-7702 cells) but obvious killing effects murine breast cancer cells (4T1 cells). The combined chemo-photothermal therapeutic effect on 4T1 cells was successfully obtained. DOX-loaded HIT-NPs could effectively accumulate in 4T1 subcutaneous tumors after intravenous injection, and the tumor temperature rapidly increased under laser exposure, indicating the feasibility of PTT in vivo. Conclusion: The self-assembled HIT-NPs could provide a promising platform for combined chemo-photothermal cancer therapy with full biocompatibility.


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.


2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Yong-Qu Zhang ◽  
Yuan-Ke Liang ◽  
Yang Wu ◽  
Min Chen ◽  
Wei-Ling Chen ◽  
...  

AbstractNotch receptors (Notch1–4) play critical roles in tumorigenesis and metastasis of malignant tumors, including breast cancer. Although abnormal Notch activation is related to various tumors, the importance of single receptors and their mechanism of activation in distinct breast cancer subtypes are still unclear. Previous studies by our group demonstrated that Notch3 may inhibit the emergence and progression of breast cancer. PTEN is a potent tumor suppressor, and its loss of function is sufficient to promote the occurrence and progression of tumors. Intriguingly, numerous studies have revealed that Notch1 is involved in the regulation of PTEN through its binding to CBF-1, a Notch transcription factor, and the PTEN promoter. In this study, we found that Notch3 and PTEN levels correlated with the luminal phenotype in breast cancer cell lines. Furthermore, we demonstrated that Notch3 transactivated PTEN by binding CSL-binding elements in the PTEN promoter and, at least in part, inhibiting the PTEN downstream AKT-mTOR pathway. Notably, Notch3 knockdown downregulated PTEN and promoted cell proliferation and tumorigenesis. In contrast, overexpression of the Notch3 intracellular domain upregulated PTEN and inhibited cell proliferation and tumorigenesis in vitro and in vivo. Moreover, inhibition or overexpression of PTEN partially reversed the promotion or inhibition of cell proliferation induced by Notch3 alterations. In general, Notch3 expression positively correlated with elevated expression of PTEN, ER, lower Ki-67 index, and incidence of involved node status and predicted better recurrence-free survival in breast cancer patients. Therefore, our findings demonstrate that Notch3 inhibits breast cancer proliferation and suppresses tumorigenesis by transactivating PTEN expression.


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