Albumin Binding Domain Fusing R/K-X-X-R/K Sequence for Enhancing Tumor Delivery of Doxorubicin

Abstract

For the purpose of improving the tumor delivery of doxorubicin (DOX), a kind of peptide-DOXO conjugate was designed and prepared, in which the peptide composed of an albumin-binding domain (ABD) and a tumor-specific internalizing sequence (RGDK or RPARPAR) was conjugated to a (6-maleimidocaproyl) hydrazone derivative of doxorubicin (DOXO-EMCH). The doxorubicin uptake by lung cancer cell line of A549 evidenced that the conjugates are capable of being internalized through a tumor-specific sequence mediated manner, and the intracellular imaging of distribution in A549 cell demonstrated that the conjugated doxorubicin can be delivered to the cell nucleus. The A549 cell cytotoxicity of peptide-DOXO conjugates was presented with IC values and shown in the range of about 9-11 μM. Pharmacokinetics study revealed that both conjugates exhibited nearly 5.5 times longer half-time than DOX, and about 4 times than DOXO-EMCH. The in vivo growth inhibitions of the two peptide-DOXO conjugates on BALB/c nude mice bearing A549 tumor (47.78% for ABD-RGDK-DOXO and 47.09% for ABD-RPARPAR-DOXO) were much stronger than that of doxorubicin and DOXO-EMCH (24.28% and 25.67% respectively) at a doxorubicin equivalent dose. Besides, the in vivo fluorescence imaging study confirmed that the peptide markedly increased the payload accumulation in tumor tissues and indicated that albumin binding domain fusing tumor-specific sequence effectively enhanced the tumor delivery of doxorubicin and thus improved its therapeutic potency.

Conjugate of Doxorubicin to Albumin‐Binding Peptide Outperforms Aldoxorubicin

“…To the best of our knowledge, this is the first report showing that a conjugate of doxorubicin with an albumin‐binding protein domain provides a 16‐fold greater drug exposure in tumor than the free drug formulation, a 2‐fold higher maximum tolerated dose, and results in complete tumor eradication and prolonged survival with a single injection. We note that there is one published report of a somewhat different system that consists of doxorubicin conjugated to an albumin‐binding domain fused to tumor‐penetrating sequences, but despite the apparent sophistication of the design, it failed to exhibit any tumor eradication, highlighting the fact that careful design of a delivery system is critical to its success.…”

Graphene‐Based Transparent Conductive Films: Material Systems, Preparation and Applications

“…graphene to enhance the performance of graphene, although they show lower conductivity compared with ITO. Besides PEDOT:PSS, [100,[131][132][133][134][135] other polymers including PMMA, [136] polystyrene (PS), [137] 3-aminopropyltriethoxysilane (APTES), [138] PET, [139] and poly(ionic liquids) (PIL), [140] which are highly transparent in the visible region, have also been applied to the hybrid with graphene in TCFs. For instance, PEDOT:PSS has been used to delicately address the defect issues introduced during the graphene growth and transfer process, by covering the winkles and cracks of graphene films to form continuous conductive channels (Figure 22a,b).…”

Conductive Tough Hydrogel for Bioapplications

“…Compared to LCGO, this peak for PUHC is shifted toward a higher frequency from 1588 to 1595 cm −1 , suggesting the π-π interaction between LCGO and PEDOT:PSS in PUHC. [46,47] The ratio of the D-band intensity (I D ) to the G-band intensity (I G ) which is called the R values (I D /I G ), indicates the amount of structural order in graphene oxide. From Figure 8 the R-value of LCGO (1.47) is reduced compared to that of PUHC (1.36) and indicates that graphene sheets within the LCGO are more ordered and some of the sp 2 bonds have been restored.…”