Cancer-specific drug-drug nanoparticles of pro-apoptotic and cathepsin B-cleavable peptide-conjugated doxorubicin for drug-resistant cancer therapy

Biomaterials ◽  
2020 ◽  
Vol 261 ◽  
pp. 120347
Author(s):  
Man Kyu Shim ◽  
Yujeong Moon ◽  
Suah Yang ◽  
Jinseong Kim ◽  
Hanhee Cho ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Cathepsin B ◽  
Specific Drug ◽  
Drug Resistant ◽  
Drug Nanoparticles ◽  
Cleavable Peptide

scholarly journals Single cell-derived clonal analysis of human glioblastoma links functional and genomic heterogeneity

2015 ◽  
Vol 112 (3) ◽  
pp. 851-856 ◽  
Author(s):  
Mona Meyer ◽  
Jüri Reimand ◽  
Xiaoyang Lan ◽  
Renee Head ◽  
Xueming Zhu ◽  
...  
Keyword(s):  
Functional Significance ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Clonal Analysis ◽  
Specific Drug ◽  
Drug Resistant ◽  
Naive Patient ◽  
Functional Behavior ◽  
Proliferation And Differentiation ◽  
Genomic Analyses

Glioblastoma (GBM) is a cancer comprised of morphologically, genetically, and phenotypically diverse cells. However, an understanding of the functional significance of intratumoral heterogeneity is lacking. We devised a method to isolate and functionally profile tumorigenic clones from patient glioblastoma samples. Individual clones demonstrated unique proliferation and differentiation abilities. Importantly, naïve patient tumors included clones that were temozolomide resistant, indicating that resistance to conventional GBM therapy can preexist in untreated tumors at a clonal level. Further, candidate therapies for resistant clones were detected with clone-specific drug screening. Genomic analyses revealed genes and pathways that associate with specific functional behavior of single clones. Our results suggest that functional clonal profiling used to identify tumorigenic and drug-resistant tumor clones will lead to the discovery of new GBM clone-specific treatment strategies.

Codelivery for Paclitaxel and Bcl-2 Conversion Gene by PHB-PDMAEMA Amphiphilic Cationic Copolymer for Effective Drug Resistant Cancer Therapy

2017 ◽  
Vol 17 (11) ◽  
pp. 1700186 ◽  
Author(s):  
Xiaoyuan Wang ◽  
Sing Shy Liow ◽  
Qiaoqiong Wu ◽  
Chuang Li ◽  
Cally Owh ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Effective Drug ◽  
Drug Resistant

scholarly journals Cathepsin B-Overexpressed Tumor Cell Activatable Albumin-Binding Doxorubicin Prodrug for Cancer-Targeted Therapy

Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 83
Author(s):  
Hanhee Cho ◽  
Man Kyu Shim ◽  
Suah Yang ◽  
Sukyung Song ◽  
Yujeong Moon ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cathepsin B ◽  
Half Life ◽  
Albumin Binding ◽  
Normal Tissues ◽  
Cleavable Peptide ◽  
Tumor Accumulation ◽  
Maleimide Group ◽  
Cancer Targeted Therapy

Prodrugs are bioreversible medications that should undergo an enzymatic or chemical transformation in the tumor microenvironment to release active drugs, which improve cancer selectivity to reduce toxicities of anticancer drugs. However, such approaches have been challenged by poor therapeutic efficacy attributed to a short half-life and low tumor targeting. Herein, we propose cathepsin B-overexpressed tumor cell activatable albumin-binding doxorubicin prodrug, Al-ProD, that consists of a albumin-binding maleimide group, cathepsin B-cleavable peptide (FRRG), and doxorubicin. The Al-ProD binds to in situ albumin, and albumin-bound Al-ProD indicates high tumor accumulation with prolonged half-life, and selctively releases doxorubicin in cathepsin B-overexpressed tumor cells, inducing a potent antitumor efficacy. Concurrently, toxicity of Al-ProD toward normal tissues with innately low cathepsin B expression is significantly reduced by maintaining an inactive state, thereby increasing the safety of chemotherapy. This study offers a promising approach for effective and safe chemotherapy, which may open new avenues for drug design and translational medicine.

A light-controllable specific drug delivery nanoplatform for targeted bimodal imaging-guided photothermal/chemo synergistic cancer therapy

2018 ◽  
Vol 80 ◽  
pp. 308-326 ◽  
Author(s):  
Yuan Guo ◽  
Xing-Yue Wang ◽  
Yu-Li Chen ◽  
Feng-Qiu Liu ◽  
Mi-Xiao Tan ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cancer Therapy ◽  
Specific Drug ◽  
Bimodal Imaging

scholarly journals Pharmacophore hybridisation and nanoscale assembly to discover self-delivering lysosomotropic new-chemical entities for cancer therapy

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhao Ma ◽  
Jin Li ◽  
Kai Lin ◽  
Mythili Ramachandran ◽  
Dalin Zhang ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cancer Therapy ◽  
Self Assembly ◽  
The Self ◽  
Single Drug ◽  
Drug Nanoparticles ◽  
Lysosomal Dysfunction ◽  
New Chemical Entities ◽  
Autophagy Inhibition

Abstract Integration of the unique advantages of the fields of drug discovery and drug delivery is invaluable for the advancement of drug development. Here we propose a self-delivering one-component new-chemical-entity nanomedicine (ONN) strategy to improve cancer therapy through incorporation of the self-assembly principle into drug design. A lysosomotropic detergent (MSDH) and an autophagy inhibitor (Lys05) are hybridised to develop bisaminoquinoline derivatives that can intrinsically form nanoassemblies. The selected BAQ12 and BAQ13 ONNs are highly effective in inducing lysosomal disruption, lysosomal dysfunction and autophagy blockade and exhibit 30-fold higher antiproliferative activity than hydroxychloroquine used in clinical trials. These single-drug nanoparticles demonstrate excellent pharmacokinetic and toxicological profiles and dramatic antitumour efficacy in vivo. In addition, they are able to encapsulate and deliver additional drugs to tumour sites and are thus promising agents for autophagy inhibition-based combination therapy. Given their transdisciplinary advantages, these BAQ ONNs have enormous potential to improve cancer therapy.

Targeted and Sustained Corelease of Chemotherapeutics and Gene by Injectable Supramolecular Hydrogel for Drug-Resistant Cancer Therapy

2018 ◽  
Vol 40 (5) ◽  
pp. 1800117 ◽  
Author(s):  
Xuan Liu ◽  
Zibiao Li ◽  
Xian Jun Loh ◽  
Kaifeng Chen ◽  
Zhen Li ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Drug Resistant ◽  
Supramolecular Hydrogel
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