Multi-level specific targeting of cancer cells

A method of delivering at least one effector molecule to a subcellular compartment of a cell of interest, comprising:

• contacting to the cell of interest a fusion protein or covalent conjugate having a formula, from N terminus to C terminus, selected from the group consisting of:
• A-B-C-D-E,
• E-D-C-B-A,
• A-B-D-C-E;
• and
• E-C-D-B-A,
• wherein:
• A is IL-13, a mutant of IL-13, or an IL-13Rα2 binding fragment thereof;
• B is a cytosol localization element, wherein said cytosol localization element is a Pseudomonas exotoxin or diphtheria toxin translocation domain;
• C is a subcellular compartment localization signal element, wherein said subcellular compartment localization signal element is a nuclear localization element, a lysosomal localization element, or a mitochondrial localization element;
• D is a first effector molecule, wherein said first effector molecule comprises a therapeutic agent or a detectable group;
• and
• E is a second effector molecule that is present or absent and when present comprises a therapeutic agent or a detectable group,
• wherein said contacting is carried out under conditions in which said fusion protein or covalent conjugate is internalized by the cell of interest and said effector molecule is delivered to said subcellular compartment.