New approaches integrating stimuli-responsive linkers into prodrugs are currently emerging. These “smart” prodrugs can enhance the effectivity of conventional prodrugs with promising clinical applicability. Oxidative stress is central to several diseases, including cancer. Therefore, the design of prodrugs that respond to ROS stimulus, allowing a selective drug release in this condition, is fairly encouraging. Aiming to investigate the ROS-responsiveness of prodrugs containing the ROS-cleavable moiety, Thioketal (TK), we performed proof-of-concept studies by synthesizing ROS-responsive conjugate, namely mPEG-TK-Cy5, through exploiting Cy5 fluorescent dye. We demonstrated that, differently to non-ROS-responsive control conjugate (mPEG-Cy5), mPEG-TK-Cy5 shows a selective release of Cy5 in response to ROS in both, ROS-simulated conditions and in vitro on glioblastoma cells. Our results confirm the applicability of TK-technology in the design of ROS-responsive prodrugs, which constitutes a promising approach in cancer treatment. The translatability of this technology for other diseases treatment makes this a highly relevant and promising approach.

ROS-responsive “smart” polymeric conjugate: Synthesis, characterization and proof-of-concept study / Oddone, N.; Pederzoli, F.; Duskey, J. T.; De Benedictis, C. A.; Grabrucker, A. M.; Forni, F.; Vandelli, M. A.; Ruozi, B.; Tosi, G.. - In: INTERNATIONAL JOURNAL OF PHARMACEUTICS. - ISSN 0378-5173. - 570:(2019), pp. 118655-118655. [10.1016/j.ijpharm.2019.118655]

ROS-responsive “smart” polymeric conjugate: Synthesis, characterization and proof-of-concept study

Oddone N.;Pederzoli F.;Duskey J. T.;Forni F.;Vandelli M. A.;Ruozi B.;Tosi G.
2019

Abstract

New approaches integrating stimuli-responsive linkers into prodrugs are currently emerging. These “smart” prodrugs can enhance the effectivity of conventional prodrugs with promising clinical applicability. Oxidative stress is central to several diseases, including cancer. Therefore, the design of prodrugs that respond to ROS stimulus, allowing a selective drug release in this condition, is fairly encouraging. Aiming to investigate the ROS-responsiveness of prodrugs containing the ROS-cleavable moiety, Thioketal (TK), we performed proof-of-concept studies by synthesizing ROS-responsive conjugate, namely mPEG-TK-Cy5, through exploiting Cy5 fluorescent dye. We demonstrated that, differently to non-ROS-responsive control conjugate (mPEG-Cy5), mPEG-TK-Cy5 shows a selective release of Cy5 in response to ROS in both, ROS-simulated conditions and in vitro on glioblastoma cells. Our results confirm the applicability of TK-technology in the design of ROS-responsive prodrugs, which constitutes a promising approach in cancer treatment. The translatability of this technology for other diseases treatment makes this a highly relevant and promising approach.
31-ago-2019
570
118655
118655
ROS-responsive “smart” polymeric conjugate: Synthesis, characterization and proof-of-concept study / Oddone, N.; Pederzoli, F.; Duskey, J. T.; De Benedictis, C. A.; Grabrucker, A. M.; Forni, F.; Vandelli, M. A.; Ruozi, B.; Tosi, G.. - In: INTERNATIONAL JOURNAL OF PHARMACEUTICS. - ISSN 0378-5173. - 570:(2019), pp. 118655-118655. [10.1016/j.ijpharm.2019.118655]
Oddone, N.; Pederzoli, F.; Duskey, J. T.; De Benedictis, C. A.; Grabrucker, A. M.; Forni, F.; Vandelli, M. A.; Ruozi, B.; Tosi, G.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1188507
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