the most common administration method. However, the sizes of most enzymes are smaller than the kidney filtration threshold (50-60 kDa), resulting in fast renal clearance and short half-lives. [5] Also, limited by its hydrophilicity and large molecular weight, it is difficult for exogenous enzyme macromolecules to pass through the cell membrane to effectively catalyze intracellular target reactions. [6] To date, most of the clinical protein therapeutics were explored toward extracellular targets owing to the low translocation efficiency. [7] However, for enzyme therapeutics, especially for the enzyme replacement therapy, intracellular delivery is considered critical for effective therapy. [8] Typically, even if a number of enzymes are transfected into