Transformative Supramolecular Vesicles Based on Acid‐Degradable Acyclic Cucurbit[n]uril and a Prodrug for Promoted Tumoral‐Cell Uptake

Abstract

Smart supramolecular vesicles constructed by host–guest interactions between “acid‐degradable” acyclic cucurbit[n]uril (CB[n]) and a doxorubicin prodrug are reported. “Acid‐degradable” acyclic CB[n] is a high‐affinity host for several common antitumor drugs, and its degradation leads to a more dramatic decrease in binding affinity than that observed for “acid‐sensitive” hosts. Supramolecular complexation between acid‐degradable acyclic CB[n] and a doxorubicin prodrug resulted in the formation of negatively charged supramolecular vesicles. The prodrug strategy allowed doxorubicin to be conjugated to vesicles in a stable manner with a high drug‐loading ratio of 20 %. The resulting supramolecular vesicles were responsive to tumor acidity (pH 6.5). Induced by mildly acidic conditions (pH 6.5–5.5), acid‐degradable acyclic CB[n] could be degraded, and this led to a vesicle‐to‐micelle transition to form positively charged micelles. This transition resulted in a pH‐dependent change in size and surface charge, which improved tumoral‐cell uptake for doxorubicin.

Targeted micelles with chemotherapeutics and gene drugs to inhibit the G1/S and G2/M mitotic cycle of prostate cancer

“…Especially for modified polymers, the molecular weight is generally relatively large, which also leads to a relatively low drug loading rate. Other researchers reported similar values of a 10% drug loading rate [28,29], with certain reports reaching as high as 20% [30]. However, the ultrasonic method was used in preparation, and the molecular weight of the material was relatively small.…”

Displacement Induced Off–On Fluorescent Biosensor Targeting IDO1 Activity in Live Cells

“…Nevertheless, the above results encouraged the implementation of the (MP·Trp)⊂CB[8] reporter to monitor IDO1 activity in live-cell measurements. , As shown in the optical images in Figure A, both MP⊂CB[8] and (MP·Trp)⊂CB[8] showed spontaneous uptake into HeLa cells, where the latter exhibited quenched fluorescence on account of the net effect. , In the presence of IFN-γ, however, a switch-on fluorescence response was readily observed, thereby confirming the dissociation of (MP·Trp)⊂CB[8] and thus the presence of active IDO1. Instead of only physically adsorbed on the cell membrane surface or approachable in the outer cell membrane layer, the fluorescence enhancement again confirms the cellular uptake of the reporter system, which is readily accessible to the cytosolic IDO1 enzymes . As shown in Figure B, the activity of IDO1 enzymes inside HeLa cells can also be quantitatively analyzed by fluorescence-activated cell sorting (FACS).…”

“…Instead of only physically adsorbed on the cell membrane surface or approachable in the outer cell membrane layer, the fluorescence enhancement again confirms the cellular uptake of the reporter system, which is readily accessible to the cytosolic IDO1 enzymes. 32 As shown in Figure 4B, the activity of IDO1 enzymes inside HeLa cells can also be quantitatively analyzed by fluorescence-activated cell sorting (FACS). Upon incubation with (MP•Trp)⊂CB [8] and subsequent FACS analysis, approximately 30.5% of the cells pretreated with IFNγ fall within the box compared to the IDO1-negative cells (14.5%).…”

Supramolecular complexation between cucurbit[7]uril and folate and analytical applications

“…Due to its two identical carbonyl fringed portals and hydrophobic cavity, CB[n] can use direct encapsulation and release of guest molecules through cavity encapsulation or portal ion-dipole interaction. 2,3 With their unique molecular recognition properties, CB[n] and its derivatives have played a crucial role in material chemistry and supramolecular chemistry. [4][5][6] Compared with other CB[n] members, CB [7] (Figure 1) has become a new favorite in recent years because of its remarkable capabilities.…”