Question: Studies show that an influx of cysteine occurs in early endosomes (pH 6.5). Based on this observa…
Show transcribed image text Studies show that an influx of cysteine occurs in early endosomes (pH 6.5). Based on this observation, we have synthesized a novel co-polymer consisting of a hydrophobic and hydrophilic block connected by a reducible disulfide linker as shown schematically below (Fig. 1a). We show that upon addition of cysteine or dithiothreitol (a reducing agent), the co-polymer is cleaved into its constituent hydrophobic and hydrophilic homopolymers. We claim that this polymer is useful for endolysosomal delivery. To support our claim, we perform studies that evaluate macrophage uptake of nanoparticles based on the copolymer (Fig. 1b).Properties of co-polymer comprised of a hydrophobic and hydrophilic block conjugated through a reducible disulfide bond (a). Uptake and release of fluorescent nanoparticles by macrophages using a reduction-sensitive or -insensitive co-polymer. Based on the data, describe what you think is the functional mechanism of the polymer and if you think it is useful for endolysosomal delivery.If both reduction-sensitive and reduction-insensitive polymers were loaded with a protein antigen, describe the effect each would be expected to have on antigen presentation and cellular immunity?What PAMP(s) would you consider loading onto both polymers for use as vaccine adjuvants? Be specific and explain your reasoning.
Studies show that an influx of cysteine occurs in early endosomes (pH 6.5). Based on this observation, we have synthesized a novel co-polymer consisting of a hydrophobic and hydrophilic block connected by a reducible disulfide linker as shown schematically below (Fig. 1a). We show that upon addition of cysteine or dithiothreitol (a reducing agent), the co-polymer is cleaved into its constituent hydrophobic and hydrophilic homopolymers. We claim that this polymer is useful for endolysosomal delivery. To support our claim, we perform studies that evaluate macrophage uptake of nanoparticles based on the copolymer (Fig. 1b).Properties of co-polymer comprised of a hydrophobic and hydrophilic block conjugated through a reducible disulfide bond (a). Uptake and release of fluorescent nanoparticles by macrophages using a reduction-sensitive or -insensitive co-polymer. Based on the data, describe what you think is the functional mechanism of the polymer and if you think it is useful for endolysosomal delivery.If both reduction-sensitive and reduction-insensitive polymers were loaded with a protein antigen, describe the effect each would be expected to have on antigen presentation and cellular immunity?What PAMP(s) would you consider loading onto both polymers for use as vaccine adjuvants? Be specific and explain your reasoning.
