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In the present study, L-serine (Ser)-modified poly-L-lysine (PLL) was synthesized to develop a biodegradable, kidney-targeted drug carrier for efficient radionuclide therapy in renal cell carcinoma (RCC). Ser-PLL was labeled with 111 In/ 90 Y via diethylenetriaminepentaacetic acid (DTPA) chelation for biodistribution analysis/radionuclide therapy. In mice, approximately 91% of the total dose accumulated in the kidney 3 h after intravenous injection of 111 In-labeled Ser-PLL. Single-photon emission computed tomography/computed tomography (SPECT/CT) imaging showed that 111 In-labeled Ser-PLL accumulated in the renal cortex following intravenous injection. An intrarenal distribution study showed that fluorescein isothiocyanate (FITC)-labeled Ser-PLL accumulated mainly in the renal proximal tubules. This pattern was associated with RCC pathogenesis. Moreover, 111 In-labeled Ser-PLL rapidly degraded and was eluted along with the low-molecular-weight fractions of the renal homogenate in gel filtration chromatography. Continuous Ser-PLL administration over five days had no significant effect on plasma creatinine, blood urea nitrogen (BUN), or renal histology. In a murine RCC model, kidney tumor growth was significantly inhibited by the administration of the beta-emitter 90 Y combined with Ser-PLL. The foregoing results indicate that Ser-PLL is promising as a biodegradable drug carrier for kidney-targeted drug delivery and efficient radionuclide therapy in RCC.

L-Serine-Modified Poly-L-Lysine as a Biodegradable Kidney-Targeted Drug Carrier for the Efficient Radionuclide Therapy of Renal Cell Carcinoma