Antibody-mediated drug delivery

Arslan, Fatma; Atar, Kıvılcım Öztürk; Çalış, Sema

doi:10.1016/j.ijpharm.2021.120268

Cited by 59 publications

(40 citation statements)

References 94 publications

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“…To date, different type of molecules, mainly antibodies, have been used as bioligands for active target therapy to improve important aspects such as selective cellular internalization, minimizing undesired secondary effects [ 30 ]. However, nanocapsules conjugated to proteins modify their antibody 3D structure and the new derivatives are more detectable by RES, being a relatively large and a new not-natural entity, compared to natural peptides or proteins alone, or well-designed hydrophilic capsules separately [ 31 ]. Despite the fact that the use of fragments of antibodies has recently opened new possibilities to improve theses bioligand nanoparticles [ 32 ], trying to avoid its immunogenicity, this type of targeting is still in preliminary studies [ 33 ].…”

Section: Resultsmentioning

confidence: 99%

Multi-Smart and Scalable Bioligands-Free Nanomedical Platform for Intratumorally Targeted Tambjamine Delivery, a Difficult to Administrate Highly Cytotoxic Drug

Pérez-Hernández

Cuscó²,

Benítez-García

et al. 2021

Biomedicines

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Cancer is one of the leading causes of mortality worldwide due, in part, to limited success of some current therapeutic approaches. The clinical potential of many promising drugs is restricted by their systemic toxicity and lack of selectivity towards cancer cells, leading to insufficient drug concentration at the tumor site. To overcome these hurdles, we developed a novel drug delivery system based on polyurea/polyurethane nanocapsules (NCs) showing pH-synchronized amphoteric properties that facilitate their accumulation and selectivity into acidic tissues, such as tumor microenvironment. We have demonstrated that the anticancer drug used in this study, a hydrophobic anionophore named T21, increases its cytotoxic activity in acidic conditions when nanoencapsulated, which correlates with a more efficient cellular internalization. A biodistribution assay performed in mice has shown that the NCs are able to reach the tumor and the observed systemic toxicity of the free drug is significantly reduced in vivo when nanoencapsulated. Additionally, T21 antitumor activity is preserved, accompanied by tumor mass reduction compared to control mice. Altogether, this work shows these NCs as a potential drug delivery system able to reach the tumor microenvironment, reducing the undesired systemic toxic effects. Moreover, these nanosystems are prepared under scalable methodologies and straightforward process, and provide tumor selectivity through a smart mechanism independent of targeting ligands.

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Section: Resultsmentioning

confidence: 99%

Multi-Smart and Scalable Bioligands-Free Nanomedical Platform for Intratumorally Targeted Tambjamine Delivery, a Difficult to Administrate Highly Cytotoxic Drug

Pérez-Hernández

Cuscó²,

Benítez-García

et al. 2021

Biomedicines

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“…The chemical modification of enzymes offers alternatives to improve their therapeutic properties. Some examples of targeting agents that are conjugated with enzymes are antibodies and biomolecules such as proteins, peptides, saccharides, hormones, vitamins, DNA [114,115] and protein-polymer conjugates, such as PEG. PEG is a nontoxic, nonimmunogenic and amphipathic polymer widely used to modulate the activity and pharmacokinetics of enzyme drugs, affecting the immunoreactivity, immunogenicity and in vivo degradation of the enzymes [116].…”

Section: Modification Of Enzymesmentioning

confidence: 99%

“…Innovative biotechnology strategies are being developed to solve enzyme drugs drawbacks; NPs are being studied as vehicles [100], as well as virosomes [105], liposomes [106], EVs [108] and erythrocytes [113]. Additionally, molecular modifications are being carried out to improve enzyme characteristics; conjugations with biomolecules such as antibodies, DNA or metabolites are under study [114,115,118,119], and PEG modifications are being used in therapy [116]. At the same time, novel approaches to enzyme therapy applications are under study for cancer [14][15][16]60], neurodegenerative diseases [68], joint problems [56][57][58], inflammation [71,72] and infections [70].…”

Section: Future Perspectivesmentioning

confidence: 99%

Enzyme Therapy: Current Challenges and Future Perspectives

Fuente

Lombardero²,

Gómez-González

et al. 2021

IJMS

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In recent years, enzymes have risen as promising therapeutic tools for different pathologies, from metabolic deficiencies, such as fibrosis conditions, ocular pathologies or joint problems, to cancer or cardiovascular diseases. Treatments based on the catalytic activity of enzymes are able to convert a wide range of target molecules to restore the correct physiological metabolism. These treatments present several advantages compared to established therapeutic approaches thanks to their affinity and specificity properties. However, enzymes present some challenges, such as short in vivo half-life, lack of targeted action and, in particular, patient immune system reaction against the enzyme. For this reason, it is important to monitor serum immune response during treatment. This can be achieved by conventional techniques (ELISA) but also by new promising tools such as microarrays. These assays have gained popularity due to their high-throughput analysis capacity, their simplicity, and their potential to monitor the immune response of patients during enzyme therapies. In this growing field, research is still ongoing to solve current health problems such as COVID-19. Currently, promising therapeutic alternatives using the angiotensin-converting enzyme 2 (ACE2) are being studied to treat COVID-19.

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“…9,[20][21][22][23] Among said strategies, active targeting DDSs are the most promising, through which drugs are delivered to cancer tissue via linked ligands or antibodies recognizing the specific receptors on the surface of tumor cells. [24][25][26] The folate receptor is a high glucosyl phosphatidyl inositol anchor protein on the surface of primary and metastatic tumor cells, including bladder cancer cells, but almost no folate receptor is presented on the surface of normal cells. [27][28][29] However, DDSs need to be firstly directed to tumor sites in the before recognizing cell surface receptors.…”

Section: Introductionmentioning

confidence: 99%