Specific On-site Assembly of Multifunctional Magnetic Nanocargos Based on Highly Efficient and Parallelized Bioconjugation: Toward Personalized Cancer Targeting Therapy.

The rational design of particle-based cancer theranostic agents, combining diagnostic and therapeutic features in a single entity, has emerged as an effective approach toward personalized cancer therapy; however, creating a flexible assembly of specific targeting ligands with regard to a broad range of tumor tissues and cells is still challenging. Here, we present a convenient and highly variable on-site assembly strategy for the preparation of multifunctional doxorubicin (DOX)-loaded nanocargos with magnetic supraparticles (MSPs) as a core and redox-degradable poly(methylacrylic acid-co-N,N-bis(acryloyl) cystamine) (P(MAA-co-Cy) as the shell, which could be simultaneously modified with multiple targeting ligands through parallelized bioconjugation on the basis of a streptavidin-biotin (SA-BT) interaction. Under physiological conditions similar to those of the cytoplasm of tumor cells, DOX could be released in a controlled manner from these nanocargos to specific tumor sites, while dual-ligand modified nanocargos showed remarkable proliferation inhibition for the HeLa cells and the SK-OV-3 cells that overexpressed both folate as well as integrin receptors. The experimental results demonstrated that the on-site assembly strategy described herein opens access to highly efficient targeting drug delivery systems toward personalized cancer targeting therapy by incorporating functional diversity, which can be easily achieved through highly efficient and parallelized one-step bioconjugation.