A novel prodrug of pegylated methotrexate conjugates (PMCs) with a high drug-carrying capability and a redox sensitive drug release mechanism was reported for intracellular drug delivery. The PMC was structured in a H-shape with four molecules of anticancer drug methotrexate (MTX) linked to both ends of the PEG main chain via disulfide linkers, resulting in the conjugates with a high and constant drug loading efficiency of up to 26 wt%. The amphiphilic property of PMCs enables them to self-assemble into nanoparticles in aqueous solution, while the cleavable disulfide linkers allow the conjugated MTX to exert its therapeutic activity due to the fast cleavage of disulfide linkers when exposed to the intracellular concentration of glutathione (GSH). Cell proliferation assays performed with HepG2 cancer cells confirmed the pharmacological efficacy.