Biodegradable Magneto-Luminescent Mesopourous Nanoparticles as new Nano BioMedical tools in Cancer Treatment

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Biodegradable Magneto-Luminescent Mesoporous Nanoparticles As New Nanobiomedical Tools In Cancer Treatment

Publication . Marcelo, Gonçalo Alexandre dos Santos; Marques, Elisabete de Jesus Oliveira Marques; Lodeiro Y Espiño, Carlos; Lorenzo, Julia

Colorectal cancer (CRC) is the 3rd most common type of cancer worldwide and 2nd in mortality rate, accounting to 1.93 million cases and 916 000 deaths just in 2020. The development of CRC targeted therapies has been a hot topic in recent medical forums and among researchers, with the demand for non-invasive approaches, like oral ones, capable of preserving their therapeutic properties from administration to local action drastically increasing in the last decade. Its body location makes CRC a usually silent disease, whose commonly later detection and action usually lead to severe aggravations and even death. Targetability, drugs' resistance and toxicity of the said therapies are thus three of the key points for the development of effective therapies. On the other hand, the presence of cancerassociated bacterial infections and inflammations has been positively correlated with low treatment success rates and associated complications, with bacterial infections being particularly damaging in gastric and colorectal cancer. Some of the metabolites/toxins of these opportunistic bacteria have been linked to tumorigenesis and CRC drug-resistance. A conjoint therapy capable of addressing both CRC and associated bacteria, where drug preservation, null secondary toxicity and targetability are ensured. In light of the above-mentioned, herein we cover the synthesis of a new magnetofluorescent nanotherapy against both CRC and associated bacterial strains, going from the synthesis of sustainable, biocompatible, biodegradable and cheap nanocomposite particles (NANO3) to the testing of its dual drug cargo and delivery capacities, magneto-fluorescent properties and later assessment of its combined antibacterial and anti-tumor activity. The successful synthesis of new anti-CA IX targeting inhibitor as potential directing agent is also covered as a cheaper alternative to the commonly used and expensive antibodies. From an antimicrobial point of view, NANO3 showed significant activity against CRC-related bacterial strains, with their intrinsic magnetic properties potentiating a hyperthermia-assisted pH responsive release and antimicrobial therapy. The combined release of an antibiotic (i.e., ofloxacin) and an anti-tumor drug (i.e., doxorubicin) showed no hinderance on the activity of both active drugs. Accordingly, NANO3 anti-tumoral activity, arising solely from the loaded doxorubicin, was conserved and competitive to that of the free model drug. Targetability was conferred by successfully functionalizing of NANO3 with anti-EGFR and and/or anti-CA IX, the later favoring higher NANO3 uptake in HCT-116 cell line. A proof-of-concept oral delivery was also simulated, where a dual Eudragit® enteric coating successfully protected NANO3 formulations from stomachal and small intestine conditions, selectively dispensing it in colon environment and potentiating their use in a future anti-CRC oral therapy. In this thesis an optimization of a luminescent antimicrobial activity assay specific for nanoparticles was also carried out along with the evaluation of other cyanine-based antimicrobial scaffolds for a potential biomedical and food-based application.

2022Tese de doutoramento

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Fundação para a Ciência e a Tecnologia

Programa de financiamento

OE

Número da atribuição

COVID/BD/152680/2022