A novel prodrug of pegylated methotrexate conjugates (PMC) with high drug-carrying capability and redox sensitive drug release mechanism was reported for intracellular drug delivery.PMC was structured by a H-shape with four anticancer drug methotrexate (MTX) linked to both ends of PEG main chain via disulfide linkers, resulting in the conjugates with a high and constant drug loading efficiency up to 30%.The amphiphilic property of PMC enables them to self-assemble into nanomicelles in aqueous solution, while the cleavable disulfide linkers allow 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.