Methods and compositions for selection of functional aptamers

The present disclosure describes compositions and methods for selection functional aptamers. In certain embodiments, provided herein are methods of using aptamer cluster- containing particles to identify functional aptamers from an aptamer library. In certain embodiments, provided herein are functionally enriched populations of aptamers. In certain embodiments, provided herein are methods for selecting an aptamer for use in personalized cancer treatment and methods for preparing a tumor delivery system. In certain embodiments, provide herein are compositions comprise the aptamer cluster-containing particles, target cells (e.g., cancer cells, immune cells, etc.) and/or a detectable indicator of cellular function (e.g., a fluorescent indicator of apoptosis, cell proliferation, gene or protein expression, etc.).