This study presents luminescent porous silicon nanoparticles (LPSiNPs) for in vivo applications. These nanoparticles can carry a drug payload and have intrinsic near-infrared photoluminescence, enabling monitoring of both accumulation and degradation in vivo. Unlike most optically active nanomaterials, LPSiNPs self-destruct in a mouse model into renally cleared components with no evidence of toxicity. As a preliminary in vivo application, the study demonstrates tumor imaging using dextran-coated LPSiNPs (D-LPSiNPs). The results show a new type of multifunctional nanostructure with a low-toxicity degradation pathway for in vivo applications. LPSiNPs are biodegradable and have low toxicity, making them suitable for in vivo use. They can be loaded with therapeutics and degrade into harmless, renally cleared products. The study shows that LPSiNPs can be used for in vivo imaging and drug delivery. The nanoparticles are biocompatible and biodegradable, with degradation products that are naturally excreted through the kidneys. The study also shows that LPSiNPs can be used for tumor imaging, with significant accumulation in the tumor due to the enhanced permeability and retention (EPR) effect. The study demonstrates the potential of LPSiNPs for in vivo applications, including imaging and drug delivery. The nanoparticles are biocompatible, biodegradable, and have low toxicity. They can be used for in vivo imaging and drug delivery, with degradation products that are naturally excreted through the kidneys. The study also shows that LPSiNPs can be used for tumor imaging, with significant accumulation in the tumor due to the EPR effect. The results indicate that LPSiNPs are a promising candidate for clinical translation due to their biodegradability and low in vivo toxicity.This study presents luminescent porous silicon nanoparticles (LPSiNPs) for in vivo applications. These nanoparticles can carry a drug payload and have intrinsic near-infrared photoluminescence, enabling monitoring of both accumulation and degradation in vivo. Unlike most optically active nanomaterials, LPSiNPs self-destruct in a mouse model into renally cleared components with no evidence of toxicity. As a preliminary in vivo application, the study demonstrates tumor imaging using dextran-coated LPSiNPs (D-LPSiNPs). The results show a new type of multifunctional nanostructure with a low-toxicity degradation pathway for in vivo applications. LPSiNPs are biodegradable and have low toxicity, making them suitable for in vivo use. They can be loaded with therapeutics and degrade into harmless, renally cleared products. The study shows that LPSiNPs can be used for in vivo imaging and drug delivery. The nanoparticles are biocompatible and biodegradable, with degradation products that are naturally excreted through the kidneys. The study also shows that LPSiNPs can be used for tumor imaging, with significant accumulation in the tumor due to the enhanced permeability and retention (EPR) effect. The study demonstrates the potential of LPSiNPs for in vivo applications, including imaging and drug delivery. The nanoparticles are biocompatible, biodegradable, and have low toxicity. They can be used for in vivo imaging and drug delivery, with degradation products that are naturally excreted through the kidneys. The study also shows that LPSiNPs can be used for tumor imaging, with significant accumulation in the tumor due to the EPR effect. The results indicate that LPSiNPs are a promising candidate for clinical translation due to their biodegradability and low in vivo toxicity.