Significance
Due to the intrinsic heterogeneity of cancer and variability in individual patient response, personalized nanomedicine based on multi-functional carriers that integrate the functionalities of combination therapy and imaging guidance is highly demanded. Here we developed a multi-functional nanocarrier based on triblock copolymer POEG-b-PVBA-b-PFTS (POVF), which could not only be used for co-delivery of anticancer drugs PTX and Ras inhibitor FTS, but also for PET imaging guided drug delivery. The POVF carrier itself was active in inhibiting the tumor growth in vitro and in vivo. Besides, it was effective in formulating PTX with high drug loading capacity, which further enhanced the tumor inhibition effect. Meanwhile, we developed a simple and universal approach to incorporate a PET radioisotope (Zr-89 and Cu-64) into the azide-containing PTX/POVF micelles via metal-free click chemistry in aqueous solution. The radiolabeled PTX/POVF micelles exhibited excellent serum stability, rapid tumor uptake and slow clearance, which validated the feasibility of the PET image-guided delivery of PTX/POVF micelles.
Statement of significance
Due to the intrinsic heterogeneity of cancer and variability in individual patient response, personalized nanomedicine based on multi-functional carriers that integrate the functionalities of combination therapy and imaging guidance is highly demanded. Here we developed a multi-functional nanocarrier based on triblock copolymer POEG-b-PVBA-b-PFTS (POVF), which could not only be used for co-delivery of anticancer drugs PTX and Ras inhibitor FTS, but also for PET imaging guided drug delivery. The POVF carrier itself was active in inhibiting the tumor growth in vitro and in vivo. Besides, it was effective in formulating PTX with high drug loading capacity, which further enhanced the tumor inhibition effect. Meanwhile, we developed a simple and universal approach to incorporate a PET radioisotope (Zr-89 and Cu-64) into the azide-containing PTX/POVF micelles via metal-free click chemistry in aqueous solution. The radiolabeled PTX/POVF micelles exhibited excellent serum stability, rapid tumor uptake and slow clearance, which validated the feasibility of the PET image-guided delivery of PTX/POVF micelles.