Engineering folate-targeting diselenide-containing triblock copolymer as a redox-responsive shell-sheddable micelle for antitumor therapy in vivo

Abstract

On-demand drug actuation is highly desired. Redox-responsive polymeric DDSs have been shown to be able to respond and release their cargo in a selective manner when encountering a significant change in the potential difference, such as that present between cancerous and healthy tissues. This study offers an added advantage to the field of redox-responsive polymers by reporting a new type of shell-sheddable micelle based on an amphiphilic triblock co-polymer, containing diselenide as a redox-sensitive linkage. The linkage was smartly located at the hydrophilic-hydrophilic bridge in the co-polymer offering complete collapse of the micelle when exposed to the right trigger. The system was able to delay tumor growth and reduce toxicity in a breast cancer tumor model following intraperitoneal injection in mice.

<p>Manganese dioxide nanosheets: from preparation to biomedical applications</p>

“…The controlled drug delivery systems (c-DDSs) for current medications have received increasing interest from numerous chemists and clinical physicians owing to their low toxicities, broad therapeutic windows and ideal administrational efficacies compared with conventional DDSs 117–121. On-demand DDSs triggered by intrinsic physiological microenvironment changes (eg, pH,122 redox agents,123,124 enzymes,125 and heat126,127) and/or external artificially introduced stimuli128,129 (eg, light,130 laser pulses,131 magnetic/electronic fields,132 and ultrasonication133) can simultaneously diminish the side-effects of anticancer agents toward normal tissue to improve the therapeutic effects. Previous reports on DDSs have mainly focused on nanocomposites, such as magnetic composites and upconversion nanoparticles, and most of them have been magnetically functionalized mesoporous materials or hollow spherical particles with the drugs being released via changes in the pH or temperature 121,134–137.…”

Novel AIEgen-Functionalized Diselenide-Crosslinked Polymer Gels as Fluorescent Probes and Drug Release Carriers

“…As summarized in Figure 4a, the release of DOX was slow and sustained, and only 20% was released from the polymer gels after 40 h due to the blocking effect of the intermolecular hydrogen bond. In the presence of 0.001 wt.% H2O2 solution, the percentage release increased gradually with time and reached a maximum value (about 60%) within 6 h. A slower release trend could be observed when the polymer gels were immersed in 10 mM DTT and the loaded DOX release reached 25% in 20 h and about 40% in 40 h. This might be attributed to the reduction and oxidation responsive cleavage of diselenide groups oxidized into seleninic acids by H2O2 and reduced to selenols by DTT [33], which destroyed the cross-linked networks and caused quick release. Meanwhile, the fluorescence emission based on TPE (λex = 340 nm) of the DOX-loaded gels in a PB solution was tested during the redox release, as shown in Figure 4b.…”

“…Selenium-containing polymers showed versatile responsive behaviors to multiple stimuli, such as oxidation, reduction, and irradiation [24][25][26][27][28][29], which make them potentially useful as bio-building blocks. Redox responsiveness is an important property of diselenide-containing polymers [30][31][32][33]. Compared with the disulfide bond, the lower binding energy of the selenium bond (172 kJ mol −1 ) gives them a high sensitivity to oxidative and reductive stimuli.…”

Chitosan-Based Nanomaterials for Drug Delivery

“…The internal environment of the human body is complex and not static, and the environment of the lesion will also affect the development of the diseases [ 83 ]. The pH [ 7 ], cytokine [ 60 ], enzymes [ 5 ], ion concentration, and cell membrane pore size may vary in different tissues and organs to some extent.…”