Degradable Hollow Mesoporous Silicon/Carbon Nanoparticles for Photoacoustic Imaging-Guided Highly Effective Chemo-Thermal Tumor Therapy in Vitro and in Vivo

Gold nanoparticles offer the possibility to combine both imaging and therapy of otherwise difficult to treat tumors. To validate and further improve their potential, we describe the use of gold nanostars that were functionalized with a polyethyleneglycol-maleimide coating for in vitro and in vivo photoacoustic imaging (PAI), computed tomography (CT), as well as photothermal therapy (PTT) of cancer cells and tumor masses, respectively. Nanostar shaped particles show a high absorption coefficient in the near infrared region and have a hydrodynamic size in biological medium around 100 nm, which allows optimal intra-tumoral retention. Using these nanostars for in vitro labeling of tumor cells, high intracellular nanostar concentrations could be achieved, resulting in high PAI and CT contrast and effective PTT. By injecting the nanostars intratumorally, high contrast could be generated in vivo using PAI and CT, which allowed successful multi-modal tumor imaging. PTT was successfully induced, resulting in tumor cell death and subsequent inhibition of tumor growth. Therefore, gold nanostars are versatile theranostic agents for tumor therapy.

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Internal and External Triggering Mechanism of “Smart” Nanoparticle-Based DDSs in Targeted Tumor Therapy

Current Pharmaceutical Design ◽

10.2174/1381612824666180510094607 ◽

2018 ◽

Vol 24 (15) ◽

pp. 1639-1651 ◽

Cited By ~ 2

Author(s):

Xian-ling Qian ◽

Jun Li ◽

Ran Wei ◽

Hui Lin ◽

Li-xia Xiong

Keyword(s):

Targeted Delivery ◽

Tumor Therapy ◽

Burst Release ◽

Tumor Site ◽

Chemotherapeutic Drugs ◽

Triggering Mechanism ◽

Triggering Factors ◽

Or Genes

Background: Anticancer chemotherapeutics have a lot of problems via conventional Drug Delivery Systems (DDSs), including non-specificity, burst release, severe side-effects, and damage to normal cells. Owing to its potential to circumventing these problems, nanotechnology has gained increasing attention in targeted tumor therapy. Chemotherapeutic drugs or genes encapsulated in nanoparticles could be used to target therapies to the tumor site in three ways: “passive”, “active”, and “smart” targeting. Objective: To summarize the mechanisms of various internal and external “smart” stimulating factors on the basis of findings from in vivo and in vitro studies. Method: A thorough search of PubMed was conducted in order to identify the majority of trials, studies and novel articles related to the subject. Results: Activated by internal triggering factors (pH, redox, enzyme, hypoxia, etc.) or external triggering factors (temperature, light of different wavelengths, ultrasound, magnetic fields, etc.), “smart” DDSs exhibit targeted delivery to the tumor site, and controlled release of chemotherapeutic drugs or genes. Conclusion: In this review article, we summarize and classify the internal and external triggering mechanism of “smart” nanoparticle-based DDSs in targeted tumor therapy, and the most recent research advances are illustrated for better understanding.

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Diaphanous related formin 3 knockdown suppresses cell proliferation and metastasis of osteosarcoma cells

Discover Oncology ◽

10.1007/s12672-021-00415-8 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Zehua Zhang ◽

Fei Dai ◽

Fei Luo ◽

Wenjie Wu ◽

Shuai Zhang ◽

...

Keyword(s):

Cell Proliferation ◽

Tumor Therapy ◽

Disease Free Survival ◽

Tumor Stage ◽

Migration And Invasion ◽

Osteosarcoma Cell ◽

Proliferation And Metastasis ◽

New Biomarkers

AbstractOsteosarcoma is a malignant osteoblastic tumor that can gravely endanger the lives and health of children and adolescents. Therefore, there is an urgent need to explore new biomarkers for osteosarcoma and determine new targeted therapies to improve the efficacy of osteosarcoma treatment. Diaphanous related formin 3 (DIAPH3) promotes tumorigenesis in hepatocellular carcinoma and lung adenocarcinoma, suggesting that DIAPH3 may be a target for tumor therapy. To date, there have been no reports on the function of DIAPH3 in osteosarcoma. DIAPH3 protein expression in osteosarcoma tissues and healthy bone tissues adjacent to cancer cells was examined by immunohistochemical staining. DIAPH3 mRNA expression correlates with overall survival and reduced disease-free survival. DIAPH3 protein is upregulated in osteosarcoma tissues, and its expression is significantly associated with tumor size, tumor stage, node metastasis, and distant metastasis. Functional in vitro experiments revealed that DIAPH3 knockdown suppressed cell proliferation and suppressed cell migration and invasion of osteosarcoma cell lines MG-63 and HOS. Functional experiments demonstrated that DIAPH3 knockdown inhibited subcutaneous tumor growth and lung metastasis in vivo. In conclusion, DIAPH3 expression can predict the clinical outcome of osteosarcoma. In addition, DIAPH3 is involved in the proliferation and metastasis of osteosarcoma, and as such, DIAPH3 may be a potential therapeutic target for osteosarcoma.

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Topotecan-loaded thermosensitive nanocargo for tumor therapy: In vitro and in vivo analyses

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2021.120871 ◽

2021 ◽

pp. 120871

Author(s):

Zhiyong Zhang ◽

Pan Yan ◽

Yan Zhao ◽

Mudan Ren ◽

Yarui Li ◽

...

Keyword(s):

Tumor Therapy

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In Vitro and In Vivo Multispectral Photoacoustic Imaging for the Evaluation of Chromophore Concentration

Sensors ◽

10.3390/s21103366 ◽

2021 ◽

Vol 21 (10) ◽

pp. 3366

Author(s):

Aneline Dolet ◽

Rita Ammanouil ◽

Virginie Petrilli ◽

Cédric Richard ◽

Piero Tortoli ◽

...

Keyword(s):

Remote Sensing ◽

Photoacoustic Imaging ◽

Hyperspectral Remote Sensing ◽

Reference Spectrum ◽

In Vivo Experiments ◽

Mouse Tumors ◽

Chromophore Concentration ◽

Saturation Rate

Multispectral photoacoustic imaging is a powerful noninvasive medical imaging technique that provides access to functional information. In this study, a set of methods is proposed and validated, with experimental multispectral photoacoustic images used to estimate the concentration of chromophores. The unmixing techniques used in this paper consist of two steps: (1) automatic extraction of the reference spectrum of each pure chromophore; and (2) abundance calculation of each pure chromophore from the estimated reference spectra. The compared strategies bring positivity and sum-to-one constraints, from the hyperspectral remote sensing field to multispectral photoacoustic, to evaluate chromophore concentration. Particularly, the study extracts the endmembers and compares the algorithms from the hyperspectral remote sensing domain and a dedicated algorithm for segmentation of multispectral photoacoustic data to this end. First, these strategies are tested with dilution and mixing of chromophores on colored 4% agar phantom data. Then, some preliminary in vivo experiments are performed. These consist of estimations of the oxygen saturation rate (sO2) in mouse tumors. This article proposes then a proof-of-concept of the interest to bring hyperspectral remote sensing algorithms to multispectral photoacoustic imaging for the estimation of chromophore concentration.

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Tumor-Targeting Peptides Search Strategy for the Delivery of Therapeutic and Diagnostic Molecules to Tumor Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22010314 ◽

2020 ◽

Vol 22 (1) ◽

pp. 314

Author(s):

Maria D. Dmitrieva ◽

Anna A. Voitova ◽

Maya A. Dymova ◽

Vladimir A. Richter ◽

Elena V. Kuligina

Keyword(s):

Phage Display ◽

Cell Sorting ◽

Targeted Delivery ◽

Tumor Targeting ◽

Search Strategy ◽

Tumor Therapy ◽

Therapeutic Agents ◽

Phage Libraries

Background: The combination of the unique properties of cancer cells makes it possible to find specific ligands that interact directly with the tumor, and to conduct targeted tumor therapy. Phage display is one of the most common methods for searching for specific ligands. Bacteriophages display peptides, and the peptides themselves can be used as targeting molecules for the delivery of diagnostic and therapeutic agents. Phage display can be performed both in vitro and in vivo. Moreover, it is possible to carry out the phage display on cells pre-enriched for a certain tumor marker, for example, CD44 and CD133. Methods: For this work we used several methods, such as phage display, sequencing, cell sorting, immunocytochemistry, phage titration. Results: We performed phage display using different screening systems (in vitro and in vivo), different phage libraries (Ph.D-7, Ph.D-12, Ph.D-C7C) on CD44+/CD133+ and without enrichment U-87 MG cells. The binding efficiency of bacteriophages displayed tumor-targeting peptides on U-87 MG cells was compared in vitro. We also conducted a comparative analysis in vivo of the specificity of the accumulation of selected bacteriophages in the tumor and in the control organs (liver, brain, kidney and lungs). Conclusions: The screening in vivo of linear phage peptide libraries for glioblastoma was the most effective strategy for obtaining tumor-targeting peptides providing targeted delivery of diagnostic and therapeutic agents to glioblastoma.

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Fluorescence Quenching Nanoprobes Dedicated to In Vivo Photoacoustic Imaging and High-Efficient Tumor Therapy in Deep-Seated Tissue

Small ◽

10.1002/smll.201403395 ◽

2015 ◽

Vol 11 (22) ◽

pp. 2675-2686 ◽

Cited By ~ 42

Author(s):

Huan Qin ◽

Ting Zhou ◽

Sihua Yang ◽

Da Xing

Keyword(s):

Fluorescence Quenching ◽

Photoacoustic Imaging ◽

Tumor Therapy ◽

High Efficient

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Redox-Responsive Nanocarrier Based on Heparin End-Capped Mesoporous Silica Nanoparticles for Targeted Tumor Therapy in Vitro and in Vivo

Langmuir ◽

10.1021/la501924p ◽

2014 ◽

Vol 30 (26) ◽

pp. 7867-7877 ◽

Cited By ~ 58

Author(s):

Liangliang Dai ◽

Jinghua Li ◽

Beilu Zhang ◽

Junjie Liu ◽

Zhong Luo ◽

...

Keyword(s):

Mesoporous Silica ◽

Silica Nanoparticles ◽

Mesoporous Silica Nanoparticles ◽

Tumor Therapy ◽

Redox Responsive

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Efficient Photoacoustic Imaging With Biomimetic Mesoporous Silica-Based Nanoparticles

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.762956 ◽

2021 ◽

Vol 9 ◽

Author(s):

Chuangjia Huang ◽

Xiaoling Guan ◽

Hui Lin ◽

Lu Liang ◽

Yingling Miao ◽

...

Keyword(s):

Mesoporous Silica ◽

Near Infrared ◽

Ex Vivo ◽

Photoacoustic Imaging ◽

Mesoporous Silica Nanoparticles ◽

Good Biocompatibility ◽

Targeting Ability ◽

Body Clearance

Indocyanine green (ICG), a near-infrared (NIR) fluorescent dye approved by the Food and Drug Administration (FDA), has been extensively used as a photoacoustic (PA) probe for PA imaging. However, its practical application is limited by poor photostability in water, rapid body clearance, and non-specificity. Herein, we fabricated a novel biomimetic nanoprobe by coating ICG-loaded mesoporous silica nanoparticles with the cancer cell membrane (namely, CMI) for PA imaging. This probe exhibited good dispersion, large loading efficiency, good biocompatibility, and homologous targeting ability to Hela cells in vitro. Furthermore, the in vivo and ex vivo PA imaging on Hela tumor-bearing nude mice demonstrated that CMI could accumulate in tumor tissue and display a superior PA imaging efficacy compared with free ICG. All these results demonstrated that CMI might be a promising contrast agent for PA imaging of cervical carcinoma.

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Targeted Brain Tumor Therapy by Inhibiting the MDM2 Oncogene: In Vitro and In Vivo Antitumor Activity and Mechanism of Action

Cells ◽

10.3390/cells9071592 ◽

2020 ◽

Vol 9 (7) ◽

pp. 1592

Author(s):

Surendra R. Punganuru ◽

Viswanath Arutla ◽

Wei Zhao ◽

Mehrdad Rajaei ◽

Hemantkumar Deokar ◽

...

Keyword(s):

Brain Tumor ◽

Antitumor Activity ◽

Cell Lines ◽

Tumor Therapy ◽

Single Agent ◽

M Cell ◽

In Vivo Antitumor Activity ◽

The Brain

There is a desperate need for novel and efficacious chemotherapeutic strategies for human brain cancers. There are abundant molecular alterations along the p53 and MDM2 pathways in human glioma, which play critical roles in drug resistance. The present study was designed to evaluate the in vitro and in vivo antitumor activity of a novel brain-penetrating small molecule MDM2 degrader, termed SP-141. In a panel of nine human glioblastoma and medulloblastoma cell lines, SP-141, as a single agent, potently killed the brain tumor-derived cell lines with IC50 values ranging from 35.8 to 688.8 nM. Treatment with SP-141 resulted in diminished MDM2 and increased p53 and p21cip1 levels, G2/M cell cycle arrest, and marked apoptosis. In intracranial xenograft models of U87MG glioblastoma (wt p53) and DAOY medulloblastoma (mutant p53) expressing luciferase, treatment with SP-141 caused a significant 4- to 9-fold decrease in tumor growth in the absence of discernible toxicity. Further, combination treatment with a low dose of SP-141 (IC20) and temozolomide, a standard anti-glioma drug, led to synergistic cell killing (1.3- to 31-fold) in glioma cell lines, suggesting a novel means for overcoming temozolomide resistance. Considering that SP-141 can be taken up by the brain without the need for any special delivery, our results suggest that SP-141 should be further explored for the treatment of tumors of the central nervous system, regardless of the p53 status of the tumor.

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