Development of New Targeted Nanotherapy Combined with Magneto-Fluorescent Nanoparticles against Colorectal Cancer

• Published in: International journal of molecular sciences Vol. 24; no. 7; p. 6612
• Main Authors: Marcelo, Gonçalo A, Montpeyó, David, Galhano, Joana, Martínez-Máñez, Ramón, Capelo-Martínez, José Luis, Lorenzo, Julia, Lodeiro, Carlos, Oliveira, Elisabete
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.04.2023; MDPI
• Subjects: Acetazolamide; Cancer; Carbon dioxide; Care and treatment; Cell Line, Tumor; Cetuximab - therapeutic use; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - metabolism; Cytotoxicity; Doxorubicin; Doxorubicin - therapeutic use; Drug Delivery Systems - methods; Drugs; Epidermal growth factor receptors; Fluorescence; Growth factors; Health aspects; Homeostasis; Humans; Hypoxia; Nanoparticles; Ofloxacin; Oral administration; oral formulations; target drug delivery; target nanocarriers; targeted anticancer therapy; Tumors; Spain; target drug delivery; targeted anticancer therapy; colorectal cancer; oral formulations; target nanocarriers
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24076612

The need for non-invasive therapies capable of conserving drug efficiency and stability while having specific targetability against colorectal cancer (CRC), has made nanoparticles preferable vehicles and principal building blocks for the development of complex and multi-action anti-tumoral approaches. For that purpose, we herein report the production of a combinatory anti-tumoral nanotherapy using the production of a new targeting towards CRC lines. To do so, Magneto-fluorescent NANO3 nanoparticles were used as nanocarriers for a combination of the drugs doxorubicin (DOX) and ofloxacin (OFLO). NANO3 nanoparticles' surface was modified with two different targeting agents, a newly synthesized (anti-CA IX acetazolamide derivative (AZM-SH)) and a commercially available (anti-epidermal growth factor receptor (EGFR), Cetuximab). The cytotoxicity revealed that only DOX-containing nanosystems showed significant and even competitive cytotoxicity when compared to that of free DOX. Interestingly, surface modification with AZM-SH promoted an increased cellular uptake in the HCT116 cell line, surpassing even those functionalized with Cetuximab. The results show that the new target has high potential to be used as a nanotherapy agent for CRC cells, surpassing commercial targets. As a proof-of-concept, an oral administration form of NANO3 systems was successfully combined with Eudragit enteric coating and studied under extreme conditions.