Optical properties and morphology of silica nanocapsules (ca. 40 nm of size) incorporated with multiple InP/ZnS quantum dots (QDs, ca. 3.5 nm of size) have been investigated systematically in a typical cell culture medium (Dulbecco Modified Eagle Medium, DMEM buffer) over a period of time. The stability of silica nanocapsules with multiple QDs are found to be more robust, compared to the original aqueous pristine QDs over a period of 6 h. However, their photoluminescence efficiency is decreased after 8 h, accompanied by a change in morphology of the silica capsules. This change in morphology is caused by the dissolution of silica by alkali, and alkali-earth cations in the buffer. Our results confirm that the silica nanocapsule surface modification occurs in aqueous solution, resulting in a change from hydroxyl to carboxyl group. We also discuss possible methods to further increase the stability of the silica nanocapsules in physiological solutions.