No abstract

All drugs for cancer therapy face several transportation barriers on their tortuous journey to the action sites. To overcome these barriers, an effective drug delivery system for cancer therapy is imperative. Here, we develop a drug self-delivery system for cancer therapy, in which anticancer drugs can be delivered by themselves without any carriers. To demonstrate this unique approach, an amphiphilic drug-drug conjugate (ADDC) has been synthesized from the hydrophilic anticancer drug irinotecan (Ir) and the hydrophobic anticancer drug chlorambucil (Cb) via a hydrolyzable ester linkage. The amphiphilic Ir-Cb conjugate self-assembles into nanoparticles in water and exhibits longer blood retention half-life compared with the free drugs, which facilitates the accumulation of drugs in tumor tissues and promotes their cellular uptake. A benefit of the nanoscale characteristics of the Ir-Cb ADDC nanoparticles is that the multidrug resistance (MDR) of tumor cells can be overcome efficiently. After cellular internalization, the ester bond between hydrophilic and hydrophobic drugs undergoes hydrolysis to release free Ir and Cb, resulting in an excellent anticancer activity in vitro and in vivo.

The in situ ATRP (atom transfer radical polymerization) "grafting from" approach was successfully applied to graft poly(methyl methacrylate) (PMMA) onto the convex surfaces of multiwalled carbon nanotubes (MWNT). The thickness of the coated polymer layers can be conveniently controlled by the feed ratio of MMA to preliminarily functionalized MWNT (MWNT-Br). The resulting MWNT-based polymer brushes were characterized and confirmed with FTIR, 1H NMR, SEM, TEM, and TGA. Moreover, the approach has been extended to the copolymerization system, affording novel hybrid core-shell nanoobjects with MWNT as the core and amphiphilic poly(methyl methacrylate)-block-poly(hydroxyethyl methacrylate) (PMMA-b-PHEMA) as the shell. The approach presented here may open an avenue for exploring and preparing novel carbon nanotubes-based nanomaterials and molecular devices with tailor-made structure, architecture, and properties.

Using a modified definition, the average degree of branching, DB, the fraction of branchpoints, FB, as well as the fractions of various structural units are calculated as a function of conversion of double bonds for hyperbranched polymers formed by self-condensing vinyl polymerization (SCVP) of monomers (or "inimers") with the general structure AB*, where A is a vinyl group and B* is an initiating group. The results are compared to those for the polycondensation of AB2-type monomers. At full conversion, DB is somewhat smaller for SCVP (DB∞ ≈ 0.465) than for AB2 systems (DB∞ ) 0.5). There are two kinds of linear groups in SCVP whereas there is only one kind in AB2 systems. Since there are two different active centers in SCVP, i.e., initiating B* and propagating A* centers, the effect of nonequal reactivities on DB is also discussed. At a reactivity ratio of the two kinds of active centers, r ) kA/kB ≈ 2.59, a maximum value of DB∞ ) 0.5 is reached. For the limiting case r << 1, a linear polymer resembling a polycondensate will be formed whereas for r >> 1 a weakly branched vinyl polymer is expected. NMR experiments allow for the determination of reactivity ratio r.

The macroscopic molecular self-assembly of an amphiphilic hyperbranched copolymer in acetone generated multiwalled tubes millimeters in diameter and centimeters in length. The thickness of the tube walls approaches 400 nanometers, and the walls have an inhomogeneous lamella structure that alternates between ordered hydrophilic domains and amorphous, partly irregular hydrophilic domains.

The molecular weight distribution (MWD) and its moments are calculated for hyperbranched polymers formed by self-condensing vinyl polymerization (SCVP) of monomers (“inimers”) with the general structure AB*, where A is a vinyl group and B* is an initiating group. The calculated MWD is extremely broad, the polydispersity index (PDI) being equal to the number-average degree of polymerization:  P̄ w/P̄ n = P̄ n. It is twice as broad as that for the polycondensation of AB2 type monomers. If the fraction of unreacted monomer is not taken into account, the MWD becomes somewhat narrower, P̄‘w/P̄‘n ≈ 0.40P̄‘n. The kinetics of the polymerization process are first order with respect to the concentration of vinyl groups; P̄ n, P̄ w, and PDI increase exponentially with time. Comparison of the theoretical results with experimental data indicates that the rate constant of addition of an active center to a vinyl group decreases with increasing degree of polymerization. Since there are two different active centers in SCVP, namely initiating ones, B*, and propagating ones, A*, nonequal reactivities of the two centers (k A ≠ k B) have a strong effect on kinetics and MWD. The MWD narrows down to P̄ w/P̄ n = 2 for k A ≪ k B (corresponding to the common polycondensation of AB monomers) but broadens for k B > k A. Several deviations from ideal behavior are discussed.

Hyperbranched polymers (HBPs) are highly branched macromolecules with a three-dimensional dendritic architecture. Due to their unique topological structure and interesting physical/chemical properties, HBPs have attracted wide attention from both academia and industry. In this paper, the recent developments in HBP self-assembly and their biomedical applications have been comprehensively reviewed. Many delicate supramolecular structures from zero-dimension (0D) to three-dimension (3D), such as micelles, fibers, tubes, vesicles, membranes, large compound vesicles and physical gels, have been prepared through the solution or interfacial self-assembly of amphiphilic HBPs. In addition, these supramolecular structures have shown promising applications in the biomedical areas including drug delivery, protein purification/detection/delivery, gene transfection, antibacterial/antifouling materials and cytomimetic chemistry. Such developments promote the interdiscipline researches among surpramolecular chemistry, biomedical chemistry, nano-technology and functional materials.

Herein, we report a novel Janus particle and supramolecular block copolymer consisting of two chemically distinct hyperbranched polymers, which is coined as Janus hyperbranched polymer. It is constructed by the noncovalent coupling between a hydrophobic hyperbranched poly(3-ethyl-3-oxetanemethanol) with an apex of an azobenzene (AZO) group and a hydrophilic hyperbranched polyglycerol with an apex of a β-cyclodextrin (CD) group through the specific AZO/CD host-guest interactions. Such an amphiphilic supramolecular polymer resembles a tree together with its root very well in the architecture and can further self-assemble into unilamellar bilayer vesicles with narrow size distribution, which disassembles reversibly under the irradiation of UV light due to the trans-to-cis isomerization of the AZO groups. In addition, the obtained vesicles could further aggregate into colloidal crystal-like close-packed arrays under freeze-drying conditions. The dynamics and mechanism for the self-assembly of vesicles as well as the bilayer structure have been disclosed by a dissipative particle dynamics simulation.