Polybenzofulvene derivatives bearing dynamic binding sites as potential anticancer drug delivery systems

Abstract

In order to obtain new advanced functional materials capable of recognizing drug molecules, the polybenzofulvene backbone of molecular brush poly-6-MOEG-9-TM-BF3k has been functionalized with a "synthetic dynamic receptor" composed of two 1-adamantylurea moieties linked together by means of a dipropyleneamino bridge as in Meijer's bis(adamantylurea) pincer (BAUP). This functional material, bearing synthetic receptors potentially capable of recognizing/loading and then delivering drug molecules, was used to prepare colloidal drug delivery systems (by means of soft interaction with BAUP) for delivering the model anti-cancer drug doxorubicin (DOXO). The resulting nanostructured drug delivery systems containing the physically loaded drug were characterized in terms of drug loading and release, dimensions and zeta potential, and in vitro cell activity and uptake on two different cell lines (i.e. the human bronchial epithelial 16HBE and the human colon cancer HCT116). On normal cells, free DOXO was found to be more cytotoxic than DOXO-loaded nanogels at the higher tested concentration and, only on cancer cells, DOXO-loaded nanogels show similar or slightly higher cytotoxicity values than free DOXO, suggesting potential advantages in the treatment of cancer. These results were supported by fluorescence microscopy studies, which suggested that DOXO-loaded nanogels provide an extracellular reservoir of the drug, which is gradually released and internalized within the cells.

Hyaluronan Graft Copolymers Bearing Fatty-Acid Residues as Self-Assembling Nanoparticles for Olanzapine Delivery

“…In particular, an HA-FA-Pg derivative with 2-3 FA residues bearing a propargyl group was successfully used in the covalent coating of inorganic magnetite nanoparticles [12]. Moreover, an HA-FA-Pg derivative bearing 4-5 FA residues was used in the covalent coating of a π-stacked polybenzofulvene derivative [13][14][15][16][17][18][19] to prepare the intriguing organic material TCPB (Figure 1) [20].…”

Densely PEGylated Polybenzofulvene Brushes for Potential Applications in Drug Encapsulation

“…In these complexes, the protein–polymer interaction was assumed to occur by non-specific adsorption onto the surface of the hydrogel particles. Moreover, other PPBFB derivatives showed the capability of loading and delivering doxorubicin to cancer cells [30,34,35,36]. The carrier features of PPBFB depend on the structure and composition of the polymeric material, so that variations of these characteristics should modify its self-assembling properties, loading capacity and targeting properties.…”

“…Very interestingly, the drug delivery systems obtained with these PPBFB derivatives appeared to show biocompatible and potentially bioresorbable features. Thus, in a higher level of macromolecular organization, the architecture of poly-6-MOEG-9-TM- BF3k was used in the development of a PPBFB copolymer (i.e., poly-6-MOEG-9-TM- BF3k -co-6-BAUP-TM- BF3k ) bearing dynamic binding sites (BAUP = bis(adamantylurea) pincer) [31,32,33], capable of interacting with the anticancer drug doxorubicin [34]. This functional material was used to generate biocompatible gel nanoparticles showing dimensions around 200 nm, and capable of transporting and releasing the anticancer drug to tumor cells [34].…”

“…Thus, in a higher level of macromolecular organization, the architecture of poly-6-MOEG-9-TM- BF3k was used in the development of a PPBFB copolymer (i.e., poly-6-MOEG-9-TM- BF3k -co-6-BAUP-TM- BF3k ) bearing dynamic binding sites (BAUP = bis(adamantylurea) pincer) [31,32,33], capable of interacting with the anticancer drug doxorubicin [34]. This functional material was used to generate biocompatible gel nanoparticles showing dimensions around 200 nm, and capable of transporting and releasing the anticancer drug to tumor cells [34]. Finally, in the attempt of exploiting the potential targeting features of hyaluronic acid (HA), the tri-component polybenzofulvene brush ( TCPB ) material was developed as a third-generation PPBFB [35].…”

Electrochemical and optoelectronic properties of terthiophene- and bithiophene-based polybenzofulvene derivatives

“…5,6 On the other side, polybenzofulvene derivatives belong to a different class of conjugated polymers. [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] In fact, by virtue of their p-electron systems stacked along the polymer chain, 17 they are through-space conjugated polymers, which showed signicant hole-transporting features. Moreover, the structure of benzofulvene monomeric unities were modulated in order to obtain materials for the production of optoelectronic devices such as OLEDs.…”