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1.
J Pharm Sci ; 113(7): 1865-1873, 2024 Jul.
Article En | MEDLINE | ID: mdl-38342338

Here, a novel targeted nanostructure complex was designed as an alternative to the traditional treatment approaches for breast cancer. A delivery system utilizing CuS nanoparticles (CuS NPs) was developed for the purpose of targeted administration of doxorubicin (Dox), an anticancer agent. To regulate Dox release, chitosan (CS), a biodegradable and hydrophilic polymer with biocompatible properties, was applied to coat the Dox-loaded CuS NPs. Furthermore, AS1411 aptamer, served as a targeting agent for breast cancer cells (MCF-7 and 4T1 cells), was conjugated with CS-Dox-CuS NPs effectively. To assess the effectiveness of APT-CS-CuS NPs, various methods such as flow cytometry analysis, MTT assay, fluorescence imaging, and in vivo antitumor efficacy were employed. The hollow core and porous surface of CuS NPs improved the Dox loading capacity and entrapment efficiency (almost 100%). The rate of drug release at the tumor site (citrate buffer with pH 5.6) exhibited a marked increase in comparison to that observed within the physiological environment (phosphate buffer with pH 7.4). The targeted formulation (APT-CS-Dox-CuS NPs) significantly increased cytotoxicity of the Dox payload in target cells, including 4T1 (p ≤ 0.0001 (****)) and MCF7 (p ≤ 0.01 (**)) cells compared to CHO cells. Moreover, the ability of tumor growth inhibition of the targeted system was significantly (p ≤ 0.05 (*)) more than free Dox in tumor-bearing mice. The findings indicate that the targeted formulation augmented effectiveness and specificity while minimizing harm to non-targeted cells, signifying its potential as a sophisticated cancer drug delivery system.


Aptamers, Nucleotide , Chitosan , Doxorubicin , Nanoparticles , Doxorubicin/administration & dosage , Doxorubicin/pharmacology , Doxorubicin/pharmacokinetics , Doxorubicin/chemistry , Chitosan/chemistry , Animals , Humans , Aptamers, Nucleotide/chemistry , Aptamers, Nucleotide/administration & dosage , Female , Nanoparticles/chemistry , Mice , MCF-7 Cells , Cell Line, Tumor , Antibiotics, Antineoplastic/administration & dosage , Antibiotics, Antineoplastic/pharmacokinetics , Antibiotics, Antineoplastic/pharmacology , Antibiotics, Antineoplastic/chemistry , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Drug Delivery Systems/methods , Mice, Inbred BALB C , Drug Liberation , Drug Carriers/chemistry , Cricetulus , CHO Cells , Copper , Oligodeoxyribonucleotides
2.
J Drug Target ; 31(9): 986-997, 2023 12.
Article En | MEDLINE | ID: mdl-37869893

Chemotherapy has been widely acknowledged as a primary approach for cancer treatment. However, the administration of chemotherapy agents is often limited by their adverse effects that result from an inability to distinguish between healthy and malignant cells. As such, utilising nanocarriers in targeted drug delivery can significantly reduce these side effects while enhancing therapeutic efficacy. Herein, we developed copper sulphide nanoparticles (CuSNPs) loaded with epirubicin (Epi) coated by polyarginine and 5TR1 aptamer (CEPA) to target mucin-1 which is overexpressed on various types of cancer cells. MTT results revealed that CEPA significantly induced cytotoxicity of the drug in desired cell lines (C26 and MCF-7, mucin+) compared to CEPA-treated CHO cells (non-target, mucin-), verifying the targeting ability of CEPA complex. The obtained results from both flow cytometry analysis and cell imaging demonstrated that CEPA complex had successful internalisation in both target cell lines but no internalisation in CHO cell line. The result of in vivo assay showed more tumour inhibition and more accumulation in tumour tissue for CEPA complex in comparison to free Epi. To conclude, the CEPA complex has demonstrated superior efficacy and fewer adverse reactions compared to Epi. This indicates a promising and effective strategy for treating cancer.


Copper , Nanoparticles , Cricetinae , Animals , Humans , Epirubicin/pharmacology , Epirubicin/therapeutic use , Cricetulus , Cell Line, Tumor , MCF-7 Cells , Drug Delivery Systems/methods , Mucins
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