Journal
BIOMACROMOLECULES
Volume 23, Issue 1, Pages 276-290Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.biomac.1c01264
Keywords
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Funding
- Czech Science Foundation [20-21421S]
- Ministry of Education, Youth and Sports of the Czech Republic [LM2018124, CZ. 02.1.01/0.0/0.0/16_013/0001821, UJEP-IGA-TC-2019-53-01-2, COST LTC19049]
- European Union-European Structural and Investments Funds [CZ.02.1.01/0.0/0.0/17_048/0007411]
- FCT-Fundacao para a Ciencia e a Tecnologia, Portugal [UIDB/00674/2020, UIDP/00674/2020]
- ARDITI-Agencia Regional para o Desenvolvimento da Investigacao Tecnologia e Inovacao [M1420-01-0145-FEDER-000005-CQM+]
- FCT Ph.D. Grant [2020.04679.BD]
- COST (European Cooperation in Science and Technology) [CA 17140]
- Fundação para a Ciência e a Tecnologia [2020.04679.BD] Funding Source: FCT
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This study presents a stable glycodendrimer (glyco-DDM) series with excellent biocompatibility and potential applications in drug delivery, particularly showing promising results in encapsulating anticancer agents. The glyco-DDM/DOX complexes exhibit gradual and pH-dependent release profiles, preferential internalization in cancer cells, and promising cytotoxic effects on cancer cell lines. The results suggest that novel glycoDDMs and their drug complexes hold great promise in drug delivery and related applications.
The complexity of drug delivery mechanisms calls for the development of new transport system designs. Here, we report a robust synthetic procedure toward stable glycodendrimer (glyco-DDM) series bearing glucose, galactose, and oligo(ethylene glycol)-modified galactose peripheral units. In vitro cytotoxicity assays showed exceptional biocompatibility of the glyco-DDMs. To demonstrate applicability in drug delivery, the anticancer agent doxorubicin (DOX) was encapsulated in the glyco-DDM structure. The anticancer activity of the resulting glyco-DDM/DOX complexes was evaluated on the noncancerous (BJ) and cancerous (MCF-7 and A2780) cell lines, revealing their promising generation- and concentration- dependent effect. The glycoDDM/DOX complexes show gradual and pH-dependent DOX release profiles. Fluorescence spectra elucidated the encapsulation process. Confocal fluorescence microscopy demonstrated preferential cancer cell internalization of the glyco-DDM/DOX complexes. The conclusions were supported by computer modeling. Overall, our results are consistent with the assumption that novel glycoDDMs and their drug complexes are very promising in drug delivery and related applications.
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