Targeted drug delivery using micro-nano robots (MNRs) is a rapidly advancing and promising field in biomedical research. MNRs enable precise delivery of drugs, addressing a wide range of healthcare needs. However, the application of MNRs in vivo is limited by power issues and specificity in different scenarios. Additionally, the controllability and biological safety of MNRs must be considered. To overcome these challenges, researchers have developed bio-hybrid micro-nano motors that offer improved accuracy, effectiveness, and safety for targeted therapies. These bio-hybrid micro-nano motors/robots (BMNRs) use a variety of biological carriers, blending the benefits of artificial materials with the unique features of different biological carriers to create tailored functions for specific needs. This review aims to give an overview of the current progress and application of MNRs with various biocarriers, while exploring the characteristics, advantages, and potential hurdles for future development of these bio-carrier MNRs.

Osteosarcoma (OS) is an aggressive malignant bone tumor with limited therapeutic options and low response to immunotherapy. OS rarity slows clinical translation, highlighting the need for models that bridge patient-derived xenograft (PDX) systems and next-generation platforms. Here, we establish an OS PDX-organoid interactive biobank by self-assembling single-cell suspensions into individualized OS organoids (iOSs). iOS models recapitulate OS spatial and architectural features at millimeter scale in vitro and as xenografts and maintain functional pairing with matched PDX models. We validate iOS fidelity using histopathology, spatial features, genomics, transcriptomics, and pharmacogenomics. By reconstructing T cell infiltration in PDX-derived iOS models, we model treatment-associated immune responses and support immunotherapy translational studies. Using paired iOS-PDX models, we show that a PRMT5^MTA inhibitor enhances immunotherapy response in chromosome 9p21.3-deleted OS.