The present invention provides refillable drug delivery devices. The invention is based in part on the development of systemically administered drug payloads that home to and refill resident, e.g., previously administered/implanted, drug delivery systems, e.g., hydrogel drug delivery systems. In one aspect, the drug delivery depots of the invention are systemically administered, e.g., enterally administered or parenterally administered. The invention provides a method of nanotherapeutic drug delivery, e.g., a DNA nanotechnology-based approach for blood-based drug refilling of intra-tumor drug depots.
