Magnetic medical microrobots with memory-capable genetic circuits

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Abstract
Autonomous microrobots can reach hard-to-access regions in the human body for minimally invasive therapy. However, their microscale size limits the integration of on-board memory, making their operation dependent on external controls. Here, we develop a magnetic probiotic microrobot integrated with memory-capable genetic circuit to execute autonomous antitumor treatment. Through a one-time magnetic hyperthermia trigger, the biological thermal sensor in the microrobot perceives temperature change and activates the memory module Bxb1-ssrA- attB -P7- attP , transferring the microrobots into a therapeutic state to continuously degrade fibrin and soften the tumor microenvironment. The genetic memory remains active for at least 12 days. A synergy toward deep tumor penetration is subsequently established between the memory-encoded softening and the physical penetration through magnetically controlled wave-like locomotion of microrobots. Compared with memory-absent microrobots, the proposed microrobots achieve a 6.70-fold tumor matrix stiffness reduction and boost in vivo anticancer efficacy from 21.86 to 87.52%. Beyond oncology, the proposed system establishes a generalizable framework of memory-encoded medical microrobots.
Funding Information
  • Natural Science Foundation of Shanghai Municipality (22ZR1462800)
  • National Natural Science Foundation of China (82022039)
  • Ministry of Science and Technology of the People's Republic of China (2021YFA1201400)
  • National Natural Science Foundation of China (52405323)
  • National Natural Science Foundation of China (12350710786)
  • Science and Technology Commission Foundation of Shanghai (21XD1423900)
  • Shanghai Municipal Education Commission Innovative Program (2023ZKZD27)
  • Shanghai “Intelligent Science and Technology” IV-class peak discipline “Interdisciplinary Innovation and Education Integration Fund”
  • Shanghai Pilot Program for Basic Research, Natural Science Foundation of Shanghai (Mechanics and Emergent behavior of Collective Physical Systems)
  • Science and Technology Commission Foundation of Shanghai (25XF3200900)

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