Nanomedicine is revolutionizing the treatment of cancer and has achieved unprecedented outcomes over the past decades. The accumulation of Nanoparticles (NPs) in different tumors relies mainly on the Enhanced Permeability and Retention (EPR) effect benefiting from the wide fenestrae of the tumor vasculature and the lack of lymphatic drainage. However, the EPR effect is recognized as a heterogeneous phenomenon resulting in heterogeneous outcomes of clinical trials. Extensive efforts are exerted to enhance the outcomes of nanomedicine in a larger cohort of patients by employing active targeting strategies. However, actively targeted NPs accumulate in tumors by the EPR effect and hence fail to achieve convincing therapeutic outcomes. These obstacles are gradually being removed by improving the understanding of the Tumor Microenvironment (TME) and the mechanistic interaction of the NPs with its different components. In this review, we provide detailed insights into the past concerns of drug targeting, the current trends of TME reengineering, and the future implications for overcoming past hurdles. Strategies explored in this regard included the use of companion diagnostics and the modulation of the protein corona associated with the systemic administration of NPs and their interaction with biological macromolecules.

The present study describes the fabrication of molecularly imprinted (MI) magnetic beaded fibers using electrospinning. Rosmarinic acid was selected as exemplary yet relevant template during molecular imprinting. A “design of experiments” methodology was used for optimizing the electrospinning process. Four factors, i.e., the concentration of the biodegradable polymer (polycaprolactone), the applied voltage, the flow rate, and the collector distance were varied in a central composite design. The production process was then optimized according to the suitability of the beaded fibers during microrobot fabrication, actuation, and drug release. The optimum average fiber diameter of MI beaded fibers was determined at 857 ± 390 nm with an average number of beads at 0.011 ± 0.002 per µm². In vitro release profiles of the optimized MI beaded fibers revealed a lower burst rate and a more sustained release when compared to control fibers. Magnetic control of the MI beaded fibers was successfully tested by following selected waypoints along a star-shaped predefined trajectory. This study innovatively combines molecular imprinting technology with magnetic microrobots enabling targeted drug delivery systems that offer precise motion control via the magnetic response of microrobots along with selective uptake of a drug into the microrobot using MI beaded fibers in future.