Copolymers conjugated

Another application of this methodology is to use several different copolymers to detect multiple analytes in a single sample. Each polymer would have a different antibody attached and be precipitated at a different temperature. This appears to be possible since one copolymer that precipitates at a lower temperature does not appear to remove a copolymer with a higher LCST from solution. (J. H. Priest, unpublished observations). It is also conceivable that a DNA probe-based assay could be included with a panel of immunoassays. After removal of the various antibody-copolymer conjugates at lower temperature sodium chloride would be added, the hybridization would be performed at 55 C and the DNA-copolymer conjugates precipitated at 65 C. 

Watson KJ, Park SJ, Im JH, Nguyen SBT, Mirkin CA. DNA-block copolymer conjugates. J Am Chem Soc 2001 123 5592-5593. 

Fig. 19. Body distribution of adriamycin-HPMA copolymer conjugates 1 h after intravenous administration to rats. The distribution of a targetable conjugate containing the galactosamine moiety is compared with a conjugate without targeting moiety. Based on data from [264]...

As mentioned in Sect. 2.2.3, the biodistribution of HPMA copolymers depends on many factors. Molecular weight influences the uptake in the isolated tissue of yolk sac [266] as well as the elimination in vivo [124, 125,267,268]. Nonspecific increase in the rate of polymer uptake can be achieved by incorporation of positively charged or hydrophobic comonomers into the HPMA copolymer structure, such as methacryloyloxyethyltrimethylammonium chloride [22], N-methacryloyltyrosinamide [21], or N-[2-(4-hydroxyphenyl)ethyl]acrylamide [267]. The incorporation of hydrophobic moieties may influence the solution properties of the HPMA copolymer conjugates [132,134,269]. The interaction with the cellular surface may depend on the association number and the stability of the micelles. 

Table 7. Combined chemotherapy and photodynamic therapy of A/J mice bearing Neuro 2A neuroblastoma tumors using HPMA copolymer conjugates (from [42])...

Figure 5.5 Chemical structure of a doxorubicin-N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer conjugate...

Flanagan, P.A., Kopeckova, P., Kopecek, J. and Duncan, R. (1989) Evaluation of antibody-N-(2-hydroxypropyl)-methaciylamide copolymer conjugates as targetable drug-carriers. 1. Binding, pinocytic uptake and intracellular distribution of transferrin and anti-transferrin receptor antibody-conjugates, ilwc/iim. Biophys. Acta 993 83-91. 

Figure 1 Schematic representation of the variety of HPMA copolymer conjugate architectures and compositions under study.

Table 2 HPMA Copolymer Conjugates Containing Proteins and Peptides...

Many HPMA copolymer conjugates have been described. They contain drugs (Table 1), proteins, antibodies, and targeting ligands (Table 2). Although many subtle changes... 

Figure 2 Synthesis of HPMA copolymer conjugates via polymer analogous reaction.

Figure 5 Linking chemistries used to bind drugs and targeting residues to HPMA copolymer conjugates.

Figure 8 Release of aminoellipticine (APE) from HPMA copolymer conjugates during incubation with mixtures of isolated lysosomal enzymes (tritosomes). The results shown represent HPMA copolymer-Gly-Phe-Leu-Gly(5mol%)-APE (la,lb) HPMA copoly-mer-Gly-Phe-Leu-Gly(10 mol%)-APE (2a) and HPMA copolymer-Gly-Gly(5 mol%)-APE (3a). The numbers in bold represent the same samples but incubated without tritosomes. (From Ref. 96.)...

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