Cancer-targeted design of bioresponsive prodrug with enhanced cellular uptake to achieve precise cancer therapy

Zhang

Journal of Enzyme Inhibition and Medicinal Chemistry

et al. 2021

Chemical drug design based on the biochemical characteristics of cancer cells has become an important strategy for discovering new anti-tumour drugs to improve tumour targeting effects and reduce off-target toxicities. Colchicine is one of the most prominent and historically microtubule-targeting drugs, but its clinical applications are hindered by notorious adverse effects. In this study, we presented a novel tumour-specific conjugate 9 that consists of deacetylcolchicine (Deac), biotin, and a cleavable disulphide linker. 9 was found to exhibit potent anti-tumour activity and exerted higher selectivity between tumour and nontarget cells than Deac. The targeting moiety biotin might enhance the transport capability and selectivity of 9 to tumour cells via biotin receptor-mediated endocytosis. The tubulin polymerisation activity of 9 (with DTT) was close to the parent drug Deac. These preliminary results suggested that 9 is a high potency and reduced toxicity antitumor agent and worthy of further investigation.

Section: Introductionmentioning

confidence: 99%

“…Various biotin-conjugates (e.g. 2 and 3 , Figure 1 ) have been developed and tested in culture cells and animal models with successful results 7 , 9 , 10 . Utilising biotin as a “tumor-targeting ligand” is a promising method for designing tumour-specific conjugates.…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, and biological evaluation of biotinylated colchicine derivatives as potential antitumor agents

Zhang

Journal of Enzyme Inhibition and Medicinal Chemistry

et al. 2021

“…Drug delivery efficacy significantly depends on the cellular uptake of drugs. Effective uptake of drugs is a crucial issue for favorable treatment outcomes (Liang et al, 2018). Many studies have shown that RGD receptor a v b 3 integrin is overexpressed in cancer cells (Oe et al, 2014).…”

Section: Selective Uptake Of Rgdfc-se@sirna Nanoparticlesmentioning

confidence: 99%

Functionalized selenium nanoparticles for targeted siRNA delivery silence Derlin1 and promote antitumor efficacy against cervical cancer

et al. 2019

2020) Functionalized selenium nanoparticles for targeted siRNA delivery silence Derlin1 and promote antitumor efficacy against cervical cancer, Drug Delivery, 27:1, 15-25, ABSTRACT Small interfering RNA (siRNA) exhibits great potential as a novel therapeutic option due to its highly sequence-specific ability to silence genes. However, efficient and safe delivery carriers are required for developing novel therapeutic paradigms. Thus, the successful development of efficient delivery platforms for siRNA is a crucial issue for the development of siRNA-based drugs in cancer treatments. In this study, biocompatible selenium nanoparticles (SeNPs) were loaded with RGDfC peptide to fabricate tumor-targeting gene delivery vehicle RGDfC-SeNPs. Subsequently, RGDfC-SeNPs were loaded with Derlin1-siRNA to fabricate RGDfC-Se@siRNA, which are functionalized selenium nanoparticles. RGDfC-Se@siRNA showed greater uptake in HeLa cervical cancer cells in comparison with that in human umbilical vein endothelial cells (HUVECs), verifying the RGDfC-mediated specific uptake of RGDfC-Se@siRNA. RGDfC-Se@siRNA was capable of entering HeLa cells via clathrin-associated endocytosis, and showed faster siRNA release in a cancer cell microenvironment in comparison with a normal physiological environment. qPCR and western blotting assays both indicated that RGDfC-Se@siRNA exhibited an obvious gene silencing efficacy in HeLa cells. RGDfC-Se@siRNA suppressed the invasion, migration and the proliferation of HeLa cells, and triggered HeLa cell apoptosis. Moreover, RGDfC-Se@siRNA induced the disruption of mitochondrial membrane potentials. Meanwhile, RGDfC-Se@siRNA enhanced the generation of reactive oxygen species (ROS) in HeLa cell, suggesting that mitochondrial dysfunction mediated by ROS might play a significant role in RGDfC-Se@siRNA-induced apoptosis. Interestingly, RGDfC-SeNPs@siRNA exhibited significant antitumor activity in a HeLa tumor-bearing mouse model. Additionally, RGDfC-SeNPs@siRNA is nontoxic to main organ of mouse. The above results indicate that RGDfC-Se@siRNA provides a promising potential for cervical cancer therapy. ARTICLE HISTORY

“…Nano-sized particles are capable of working as pharmaceutical carriers for various delivery systems, orally, transdermally, or intravenously. Studies show that NPs have been tremendously used in the biomedical sector to treat diseases like diabetes [10][11][12] and cancer [13][14][15] . Among all the existing NPs, a polymer that makes good NPs is chitosan (CS) due to its special properties.…”

Section: Introductionmentioning

confidence: 99%

Untitled

2021

IJPSR

Nanotechnology can be applied to deliver and protect antioxidants in order to control the oxidative stress phenomena in several chronic pathologies. Chitosan (CS) and its carboxymethyl derivatives are smart biopolymers that are nontoxic, biocompatible, and biodegradable, and, hence, suitable for various biomedical applications, such as drug delivery gene therapy and tissue engineering. Vitis vinifera (VV) seeds are the major chemotherapeutic agent with antioxidant, antiinflammatory, antiproliferative, anticancer, and antimicrobial effects. However, the potential of these leaves as a chemotherapeutic agent is limited by their hydrophobicity and poor bioavailability. The chitosan tripolyphosphate (CS/TPP) nanoparticles have been used in this study as an alternative to encapsulate bioactive flavonoids from ethanolic extract of Vitis vinifera seeds. The Vitis vinifera seeds extract-loaded CS (CS-VVE) nanoparticles were characterized using FT-IR. The Zeta sizer and zeta potential confirmed that the particle has 216nm and 50.3mV. This study also found that the CS-VVE NPs shown anticancer activity in human colon cancer cell lines should be explored further for Cytotoxicity studies using MTT assay and tested drug-induced apoptotic process in the cell lines confirmed by the Dual staining. The CS-VVE nanoparticles showed specific toxicity towards cancer cells and non-toxicity to normal cells. It is suggested that the chitosan nanoparticles fabricated in our study may provide a suitable alternative to traditional adjuvant systems. Hence, it was observed from the present investigation that the anticancer activity of Vitis vinifera seed extract loaded chitosan nanoparticles provided a platform for treating cancer with biopolymer nanomaterials.