scholarly journals Molecularly engineered carrier-free co-delivery nanoassembly for self-sensitized photothermal cancer therapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xinzhu Shan ◽  
Xuanbo Zhang ◽  
Chen Wang ◽  
Zhiqiang Zhao ◽  
Shenwu Zhang ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Tumor Cells ◽  
Xenograft Model ◽  
Hsp90 Inhibitor ◽  
Therapeutic Modality ◽  
Gambogic Acid ◽  
Hsp90 Inhibition ◽  
Photothermal Conversion ◽  
Synergistic Cytotoxicity ◽  
Carrier Free

Abstract Background Photothermal therapy (PTT) has been extensively investigated as a tumor-localizing therapeutic modality for neoplastic disorders. However, the hyperthermia effect of PTT is greatly restricted by the thermoresistance of tumor cells. Particularly, the compensatory expression of heat shock protein 90 (HSP90) has been found to significantly accelerate the thermal tolerance of tumor cells. Thus, a combination of HSP90 inhibitor and photothermal photosensitizer is expected to significantly enhance antitumor efficacy of PTT through hyperthermia sensitization. However, it remains challenging to precisely co-deliver two or more drugs into tumors. Methods A carrier-free co-delivery nanoassembly of gambogic acid (GA, a HSP90 inhibitor) and DiR is ingeniously fabricated based on a facile and precise molecular co-assembly technique. The assembly mechanisms, photothermal conversion efficiency, laser-triggered drug release, cellular uptake, synergistic cytotoxicity of the nanoassembly are investigated in vitro. Furthermore, the pharmacokinetics, biodistribution and self-enhanced PTT efficacy were explored in vivo. Results The nanoassembly presents multiple advantages throughout the whole drug delivery process, including carrier-free fabrication with good reproducibility, high drug co-loading efficiency with convenient dose adjustment, synchronous co-delivery of DiR and GA with long systemic circulation, as well as self-tracing tumor accumulation with efficient photothermal conversion. As expected, HSP90 inhibition-augmented PTT is observed in a 4T1 tumor BALB/c mice xenograft model. Conclusion Our study provides a novel and facile dual-drug co-assembly strategy for self-sensitized cancer therapy. Graphic abstract

Hybrid Compounds & Oxidative Stress Induced Apoptosis in Cancer Therapy

2020 ◽  
Vol 27 (13) ◽  
pp. 2118-2132 ◽  
Author(s):  
Aysegul Hanikoglu ◽  
Hakan Ozben ◽  
Ferhat Hanikoglu ◽  
Tomris Ozben
Keyword(s):  
Oxidative Stress ◽  
Drug Resistance ◽  
Side Effects ◽  
Cancer Therapy ◽  
Tumor Cells ◽  
Anticancer Drugs ◽  
Chemotherapeutic Agents ◽  
Oxidation Reactions ◽  
Hybrid Compounds ◽  
Induced Apoptosis

: Elevated Reactive Oxygen Species (ROS) generated by the conventional cancer therapies and the endogenous production of ROS have been observed in various types of cancers. In contrast to the harmful effects of oxidative stress in different pathologies other than cancer, ROS can speed anti-tumorigenic signaling and cause apoptosis of tumor cells via oxidative stress as demonstrated in several studies. The primary actions of antioxidants in cells are to provide a redox balance between reduction-oxidation reactions. Antioxidants in tumor cells can scavenge excess ROS, causing resistance to ROS induced apoptosis. Various chemotherapeutic drugs, in their clinical use, have evoked drug resistance and serious side effects. Consequently, drugs having single-targets are not able to provide an effective cancer therapy. Recently, developed hybrid anticancer drugs promise great therapeutic advantages due to their capacity to overcome the limitations encountered with conventional chemotherapeutic agents. Hybrid compounds have advantages in comparison to the single cancer drugs which have usually low solubility, adverse side effects, and drug resistance. This review addresses two important treatments strategies in cancer therapy: oxidative stress induced apoptosis and hybrid anticancer drugs.

Transferrin-Conjugated Nanocarriers as Active-Targeted Drug Delivery Platforms for Cancer Therapy

2017 ◽  
Vol 23 (3) ◽  
pp. 454-466 ◽  
Author(s):  
Daniele R. Nogueira-Librelotto ◽  
Cristiane F. Codevilla ◽  
Ammad Farooqi ◽  
Clarice M. B. Rolim
Keyword(s):  
Drug Delivery ◽  
Cancer Therapy ◽  
Tumor Cells ◽  
Therapeutic Benefit ◽  
Active Targeting ◽  
Future Research ◽  
Passive Targeting ◽  
The Right ◽  
Review Current ◽  
Target Effects

A lot of effort has been devoted to achieving active targeting for cancer therapy in order to reach the right cells. Hence, increasingly it is being realized that active-targeted nanocarriers notably reduce off-target effects, mainly because of targeted localization in tumors and active cellular uptake. In this context, by taking advantage of the overexpression of transferrin receptors on the surface of tumor cells, transferrin-conjugated nanodevices have been designed, in hope that the biomarker grafting would help to maximize the therapeutic benefit and to minimize the side effects. Notably, active targeting nanoparticles have shown improved therapeutic performances in different tumor models as compared to their passive targeting counterparts. In this review, current development of nano-based devices conjugated with transferrin for active tumor-targeting drug delivery are highlighted and discussed. The main objective of this review is to provide a summary of the vast types of nanomaterials that have been used to deliver different chemotherapeutics into tumor cells, and to ultimately evaluate the progression on the strategies for cancer therapy in view of the future research.

Coconut-shell-derived activated carbon for NIR photo-activated synergistic photothermal-chemodynamic cancer therapy

2021 ◽  
Author(s):  
Gang Wu ◽  
Bao Jiang ◽  
Lin Zhou ◽  
Ao Wang ◽  
Shaohua Wei
Keyword(s):  
Activated Carbon ◽  
Cancer Therapy ◽  
Cancer Treatment ◽  
Photothermal Therapy ◽  
Carbon Nanoparticles ◽  
Coconut Shell ◽  
Photothermal Conversion

Activated carbon nanoparticles (ANs) were synthesized from coconut shell. ANs show peroxidase and photothermal conversion activities, allowing synergistic cancer treatment via chemodynamic therapy (CDT) and photothermal therapy (PTT).

scholarly journals ATRT-14. MACROPHAGE-TUMOR CELL INTERACTION PROMOTES ATRT PROGRESSION AND CHEMORESISTANCE

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii278-iii278
Author(s):  
Viktoria Melcher ◽  
Monika Graf ◽  
Marta Interlandi ◽  
Natalia Moreno ◽  
Flavia W de Faria ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Chemotherapy Resistance ◽  
Cell Communication ◽  
Xenograft Model ◽  
Cell Interaction ◽  
Immunofluorescent Staining ◽  
Genetic Traits ◽  
Rhabdoid Tumors

Abstract Atypical teratoid/rhabdoid tumors (ATRT) are pediatric brain neoplasms that are known for their heterogeneity concerning pathophysiology and outcome. The three genetically rather uniform but epigenetically distinct molecular subgroups of ATRT alone do not sufficiently explain the clinical heterogeneity. Therefore, we examined the tumor microenvironment (TME) in the context of tumor diversity. By using multiplex-immunofluorescent staining and single-cell RNA sequencing (scRNA-seq) we unveiled the pan-macrophage marker CD68 as a subgroup-independent negative prognostic marker for survival of ATRT patients. ScRNA-seq analysis of murine ATRT-SHH, ATRT-MYC and extracranial RT (eRT) provide a delineation of the TME, which is predominantly infiltrated by myeloid cells: more specifically a microglia-enriched niche in ATRT-SHH and a bone marrow-derived macrophage infiltration in ATRT-MYC and eRT. Exploring the cell-cell communication of tumor cells with tumor-associated immune cells, we found that Cd68+ tumor-associated macrophages (TAMs) are central to intercellular communication with tumor cells. Moreover, we uncovered distinct tumor phenotypes in murine ATRT-MYC that share genetic traits with TAMs. These intermediary cells considerably increase the intratumoral heterogeneity of ATRT-MYC tumors. In vitro co-culture experiments recapitulated the capability of ATRT-MYC cells to interchange cell material with macrophages extensively, in contrast to ATRT-SHH cells. We found that microglia are less involved in the exchange of information with ATRT cells and that direct contact is a prerequisite for incorporation. A relapse xenograft model implied that intermediary cells are involved in the acquisition of chemotherapy resistance. We show evidence that TAM-tumor cell interaction is one mechanism of chemotherapy resistance and relapse in ATRT.

scholarly journals Modeling the Treatment of Glioblastoma Multiforme and Cancer Stem Cells with Ordinary Differential Equations

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Kristen Abernathy ◽  
Jeremy Burke
Keyword(s):  
Stem Cells ◽  
Glioblastoma Multiforme ◽  
Cancer Therapy ◽  
Cancer Stem Cells ◽  
Differential Equations ◽  
Ordinary Differential Equations ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Tumor Recurrence ◽  
Common Event

Despite improvements in cancer therapy and treatments, tumor recurrence is a common event in cancer patients. One explanation of recurrence is that cancer therapy focuses on treatment of tumor cells and does not eradicate cancer stem cells (CSCs). CSCs are postulated to behave similar to normal stem cells in that their role is to maintain homeostasis. That is, when the population of tumor cells is reduced or depleted by treatment, CSCs will repopulate the tumor, causing recurrence. In this paper, we study the application of the CSC Hypothesis to the treatment of glioblastoma multiforme by immunotherapy. We extend the work of Kogan et al. (2008) to incorporate the dynamics of CSCs, prove the existence of a recurrence state, and provide an analysis of possible cancerous states and their dependence on treatment levels.

scholarly journals Pure drug nano-assemblies: A facile carrier-free nanoplatform for efficient cancer therapy

2021 ◽  
Author(s):  
Shuwen Fu ◽  
Guanting Li ◽  
Wenli Zang ◽  
Xinyu Zhou ◽  
Kexin Shi ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Carrier Free ◽  
Pure Drug

The Hsp70 inhibiting peptide aptamer A17 potentiates radiosensitization of tumor cells by Hsp90 inhibition

2017 ◽  
Vol 390 ◽  
pp. 146-152 ◽  
Author(s):  
Daniela Schilling ◽  
Carmen Garrido ◽  
Stephanie E. Combs ◽  
Gabriele Multhoff
Keyword(s):  
Tumor Cells ◽  
Hsp90 Inhibition ◽  
Peptide Aptamer

CSIG-17. IMMUNE MODULATORY ROLE OF TYPE I INTERFERON IN SYNGENEIC MOUSE GLIOMA MODELS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi36-vi37
Author(s):  
Evelina Blomberg ◽  
Manuela Silginer ◽  
Michael Weller
Keyword(s):  
Tumor Cells ◽  
Immune Cell ◽  
Synergistic Effects ◽  
Xenograft Model ◽  
Prolonged Survival ◽  
Type I ◽  
Syngeneic Mouse ◽  
Glioma Initiating Cells ◽  
Glioma Growth

Abstract Glioblastoma is characterized by a poor prognosis and a challenging phenotype for drug development. Although multimodal treatment, including surgery, radio- and chemotherapy is applied, the overall survival remains just above one year. Numerous clinical trials have studied targeted therapies against commonly deregulated pathways, but an efficient targeted drug is yet to be discovered. Likewise, immunotherapy has not been shown to be active. A subset of glioma tumor cells demonstrates stem-like properties; these cells are commonly referred to as glioma initiating cells (GIC). These types of cells are pluripotent and can by definition initiate and recapitulate glioma growth in experimental animals in vivo. Furthermore, these cells are often resistant to conventional therapies. Interferon β (IFN-β) is an immunomodulatory molecule with anti-cancer properties. We have previously shown that IFN-β greatly reduces sphere-formation capability of GIC. It was also confirmed that IFN-β sensitized resistant GIC to irradiation or the chemotherapeutic agent, temozolomide (TMZ). IFN-β treatment significantly prolonged survival in a xenograft model with GIC cells. In the current project, we want to use syngeneic mouse models to study the immunomodulatory effects of type I IFNs. Preliminary results indicate that abrogation of IFN signalling in tumor cells by CRISPR/Cas9 technology prolonged survival in mice only in cell lines which have substantial baseline autocrine IFN signalling. On the contrary, we did not observe a difference in survival when wild-type tumor cells were implanted in either IFNAR1 deficient or proficient hosts. Flow cytometry analysis will elucidate changes in immune cell recruitment and infiltration upon IFN signalling disruption. Moreover, we explore different treatments in combination with IFN-β as there are indications that TMZ or radiotherapy can have synergistic effects with stimulation of interferon type I signalling.

MnO2-Coated Porous Pt@CeO2 Core-Shell Nanostructures for Photoacoustic Imaging-Guided Tri-modal Cancer Therapy

Nanoscale ◽  
2021 ◽  
Author(s):  
Qing Xu ◽  
Danyang Li ◽  
Haijun Zhou ◽  
Biaoqi Chen ◽  
Junlei Wang ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Conversion Efficiency ◽  
Photoacoustic Imaging ◽  
Core Shell ◽  
Photothermal Conversion ◽  
The Core ◽  
Shell Nanostructures

We describe the synthesis of MnO2-coated porous Pt@CeO2 core–shell nanostructures (Pt@CeO2@MnO2) as a new theranostic nano-platform. The porous Pt cores endow the core–shell nanostructures with high photothermal conversion efficiency (80%)...

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