Protease inhibitors together with protease sensitive therapeutics or diagnostics are provided, which may be ionically or covalently bound, or unbound. The protease inhibitors and/or protease sensitive moiety may be provided in monomeric, homopolymeric, heteropolymeric (for each of the protease and agent) and/or block copolymeric (combining polymers of agent and inhibitor) form. The inhibitors may be native active or e.g., protease activated. Multiple protease inhibitor peptides may be used in-frame with multiple protease cleavage signals (polymeric protease activated protease inhibitors). Combination with the protease inhibitors with the protease sensitive therapeutic enhances the intact, active molecule local-regional or targeted cell or tissue concentration, peak concentration and/or duration of the therapeutic exposure, thereby increasing its therapeutic efficacy. The protease inhibitors are particularly useful for tumor-targeted therapies and for vaccines.
