scholarly journals Probing tricarbocyanine dyes for targeted delivery of anthracyclines

Author(s):  
Dmitriy Veriutin ◽  
Irina Doroshenko ◽  
Ekaterina Martynova ◽  
Ksenya Sapozhnikova ◽  
Elena Svirshchevskaya ◽  
...  

Heptamethine carbocyanine dyes possess bright fluorescence in the near IR range and affinity to cancer cells. Thus, these dyes could be utilized as fluorescent labels and vectors for drug delivery in their covalent conjugates with cytotoxic compounds. In this work we synthesized four drug-dye conjugates of tricarbocyanine dyes with anthracycline drug daunorubicin using a CuAAC reaction. Conjugates with hydrophobic dyes possess submicromolar cytotoxicity. Fluorescent imaging revealed significant accumulation of the conjugates in mitochondria, suggesting an enhancement of an additional mechanism of anthracycline cytotoxicity – generation of ROS. The hypothesis was supported by significant reduction of activity of the conjugates in presence of an antioxidant compound.

2020 ◽  
Vol 21 (11) ◽  
pp. 902-909
Author(s):  
Jingxin Zhang ◽  
Weiyue Shi ◽  
Gangqiang Xue ◽  
Qiang Ma ◽  
Haixin Cui ◽  
...  

Background: Among all cancers, lung cancer has high mortality among patients in most of the countries in the world. Targeted delivery of anticancer drugs can significantly reduce the side effects and dramatically improve the effects of the treatment. Folate, a suitable ligand, can be modified to the surface of tumor-selective drug delivery systems because it can selectively bind to the folate receptor, which is highly expressed on the surface of lung tumor cells. Objective: This study aimed to construct a kind of folate-targeted topotecan liposomes for investigating their efficacy and mechanism of action in the treatment of lung cancer in preclinical models. Methods: We conjugated topotecan liposomes with folate, and the liposomes were characterized by particle size, entrapment efficiency, cytotoxicity to A549 cells and in vitro release profile. Technical evaluations were performed on lung cancer A549 cells and xenografted A549 cancer cells in female nude mice, and the pharmacokinetics of the drug were evaluated in female SD rats. Results: The folate-targeted topotecan liposomes were proven to show effectiveness in targeting lung tumors. The anti-tumor effects of these liposomes were demonstrated by the decreased tumor volume and improved therapeutic efficacy. The folate-targeted topotecan liposomes also lengthened the topotecan blood circulation time. Conclusion: The folate-targeted topotecan liposomes are effective drug delivery systems and can be easily modified with folate, enabling the targeted liposomes to deliver topotecan to lung cancer cells and kill them, which could be used as potential carriers for lung chemotherapy.


2020 ◽  
Vol 6 (50) ◽  
pp. eabc3013
Author(s):  
Tianyuan Ci ◽  
Hongjun Li ◽  
Guojun Chen ◽  
Zejun Wang ◽  
Jinqiang Wang ◽  
...  

Live cells have been vastly engineered into drug delivery vehicles to leverage their targeting capability and cargo release behavior. Here, we describe a simple method to obtain therapeutics-containing “dead cells” by shocking live cancer cells in liquid nitrogen to eliminate pathogenicity while preserving their major structure and chemotaxis toward the lesion site. In an acute myeloid leukemia (AML) mouse model, we demonstrated that the liquid nitrogen–treated AML cells (LNT cells) can augment targeted delivery of doxorubicin (DOX) toward the bone marrow. Moreover, LNT cells serve as a cancer vaccine and promote antitumor immune responses that prolong the survival of tumor-bearing mice. Preimmunization with LNT cells along with an adjuvant also protected healthy mice from AML cell challenge.


2015 ◽  
Vol 3 (9) ◽  
pp. 1846-1855 ◽  
Author(s):  
Yunfei Mo ◽  
Haowen Wang ◽  
Jianghui Liu ◽  
Yong Lan ◽  
Rui Guo ◽  
...  

Carboxyl single-walled carbon nanotubes (SWNTs) were used to construct an innovative drug delivery system by modification with chitosan (CHI) to enhance water solubility and biocompatibility.


Polymers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1717
Author(s):  
Yedi Herdiana ◽  
Nasrul Wathoni ◽  
Shaharum Shamsuddin ◽  
I Made Joni ◽  
Muchtaridi Muchtaridi

Breast cancer remains one of the world’s most dangerous diseases because of the difficulty of finding cost-effective and specific targets for effective and efficient treatment methods. The biodegradability and biocompatibility properties of chitosan-based nanoparticles (ChNPs) have good prospects for targeted drug delivery systems. ChNPs can transfer various antitumor drugs to targeted sites via passive and active targeting pathways. The modification of ChNPs has attracted the researcher to the loading of drugs to targeted cancer cells. The objective of our review was to summarize and discuss the modification in ChNPs in delivering anticancer drugs against breast cancer cells from published papers recorded in Scopus, PubMed, and Google Scholar. In order to improve cellular uptake, drug accumulation, cytotoxicity, and selectivity, we examined different kinds of modification of ChNPs. Notably, these forms of ChNPs use the characteristics of the enhanced permeability and retention (EPR) effect as a proper parameter and different biological ligands, such as proteins, peptides, monoclonal antibodies, and small particles. In addition, as a targeted delivery system, ChNPs provided and significantly improved the delivery of drugs into specific breast cancer cells (MDA-MB-231, 4T1 cells, SK-BR-3, MCF-7, T47D). In conclusion, a promising technique is presented for increasing the efficacy, selectivity, and effectiveness of candidate drug carriers in the treatment of breast cancer.


2020 ◽  
Author(s):  
Monika Ruzycka ◽  
Patrycja Kowalik ◽  
Agata Kowalczyk ◽  
Piotr Bujak ◽  
Anna M. Nowicka ◽  
...  

Abstract Background Lung cancer is one of the most frequently diagnosed cancer all over the world and a leading cancer-related mortality. The therapy of lung cancer includes surgery, chemotherapy and radiatherapy and mailny depends on the type and stage of lung cancer characterized based on WHO guidelines. Althought the conventional chemotherapy is the main treatment option for small cell lung cancer (SCLC) and a common treatment for non-SCLC it is characterized with lack of specificity resulting to severe toxicities of normal cells and harmful side effects. Therefore, targeted drug delivery (TDD) systems have been used to reduce the systemic toxicity of some conventional chemotherapies in lung cancer. Quantum dots (QDs) are fascinating nanoscale crystals that can serve as nanocarriers in TDD due to their unique physicochemical properties. Therefore, in this paper, the as-desiged QDs, Ag-In-Zn-S-based nanoconjugates for selective doxorubicin (DOX) targeting to lung cancer cells were developed. The QD nanocrystals were modified with 11-mercaptoundecanoic acid (MUA), L-cysteine (Cys) and lipoic acid (LA) used as drug carriers for targeted delivery of DOX to A549 cells through conjugated folic acid (FA) a self-navigation molecule that docks to the folate receptors on cancer cells. The comprechensive physicochemical, cytotoxicity and genotoxicity studies were performed to characterise the novel QD-based nanocaries and their anticancer cargos. Results The results from FTIR, DLS and fluorescence quenching evidenced the successful attachment of FA to the QDs nanocrystals and DOX to the QDs-FA nanocarriers. UV-vis analysis determined the amount of FA and DOX covalently anchored to the QDs nanocrystal surface. Biological screeining revealed that QDs-FA-DOX nanoconjugates showed higher cytotoxicity in comparison to other forms of the synthesized QD samples, suggesting the cytotoxic effect of liberated DOX from the QD constructs. QD-MUA-FA-DOX occurred to be the most cytotoxic against A549 cells among nanoconjugates. In vitro scratch assay also revealed significant inhibition of A549 migration only due to treatment with QD-MUA-FA-DOX. Studies evidenced that all the nanoconjugates at IC 50 induced significantly more DNA breaks than that observed in non-treated cells. All in all, significant and the greatest cytotoxicity, genotoxicity together with inhibition of migratory potential of A549 cells was observed for QD-MUA-FA-DOX. Conclusion The studies show the therapeutic efficacy of DOX-loaded QD-based cargos suggesting their promising role as novel drug delivery systems navigating to folate receptors in lung cancer cells.


Drug Delivery ◽  
2016 ◽  
Vol 23 (5) ◽  
pp. 1838-1845 ◽  
Author(s):  
Shumei Zhang ◽  
Caixia Lu ◽  
Xiaoli Zhang ◽  
Junsheng Li ◽  
Hong Jiang

2019 ◽  
Vol 1 (1) ◽  
pp. 7
Author(s):  
R Nahrowi ◽  
A Setiawan ◽  
Noviany Noviany ◽  
I Sukmana ◽  
S D Yuwono

Paclitaxel is one of the cancer drugs that often used. These drug kills cancer cells byinhibiting mitotic cycle. The efficiency of paclitaxel is increased by the use ofnanomaterials as a carrier of paclitaxel. Nanomaterials can enhance encapsulationefficiency, improve the drug release to the target cell following nanomaterialdegradation, and improve local accumulation of drug in the cell through endocytosisreceptor. Nanomaterial that often used forencapsulation of paclitaxel is a polymerderived from natural resources such as cellulose. The advantages of cellulose as acarrier of paclitaxel are nontoxic, biodegradable, and very abundant from varioussources. One of the potential sources of cellulose for drug delivery system is cassavabaggase.Keywords: Paclitaxel, encapsulation, cell viability, nanocellulose


Author(s):  
G D Chandrethiya ◽  
P K Shelat ◽  
M N Zaveri

PEGylated gelatin nanoparticles loaded with colchicine were prepared by ethanol precipitation method. Poly-(ethylene glycol)-5000-monomethylether (MPEG 5000), a hydrophilic polymer, was used to pegylate gelatin.  Gluteraldehyde was used as cross-linking agent. To obtain a high quality product, major formulation parameters were optimized.  Spherical particles with mean particles of 193 nm were measured by a Malvern particle size analyzer. Entrapment efficiency was found to be 71.7 ± 1.4% and determined with reverse phase high performance liquid charomatography (RP-HPLC). The in vitro drug release study was performed by dialysis bag method for a period of 168 hours. Lyophilizaton study showed sucrose at lower concentrations proved the best cryoprotectant for this formulation.  Stability study revealed that lyophilized nanoparticles were equally effective (p < 0.05) after one year of storage at 2-8°C with ambient humidity. In vitro antitumoral activity was accessed using the MCF-7 cell line by MTT assay.  The IC50 value was found to be 0.034 μg/ml for the prepared formulation. The results indicate that PEGylated gelatin nanoparticles could be utilized as a potential drug delivery for targeted drug delivery of tumors.  


2020 ◽  
Vol 17 ◽  
Author(s):  
Neeraj Mittal ◽  
Varun Garg ◽  
Sanjay Kumar Bhadada ◽  
O. P. Katare

: The corona virus disease 2019 (COVID-19) has found its roots from Wuhan (China). COVID-19 is caused by a novel corona virus SARS-CoV2, previously named as 2019-nCoV. COVID-19 has spread across the globe and declared as pandemic by World health organization (WHO) on 11th March, 2020. Currently, there is no standard drug or vaccine available for the treatment, so repurposing of existing drugs is the only solution. Novel drug delivery systems (NDDS) will be boon for the repurposing of drugs. The role of various NDDS in repurposing of existing drugs for treatment of various viral diseases and their relevance in COVID-19 has discussed in this paper. It focuses on the currently ongoing research in the implementation of NDDS in COVID-19. Moreover it describes the role of NDDS in vaccine development for COVID-19. This paper also emphasizes how NDDS will help to develop the improved delivery systems (dosage forms) of existing therapeutic agents and also explore the new insights to find out the void spaces for a potential targeted delivery. So in these tough times, NDDS and nanotechnology can be a safeguard to humanity.


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