Hybrid-Actuating Macrophage-Based Microrobots for Active Cancer Therapy

Abstract

Using macrophage recruitment in tumors, we develop active, transportable, cancer theragnostic macrophage-based microrobots as vector to deliver therapeutic agents to tumor regions. The macrophage-based microrobots contain docetaxel (DTX)-loaded poly-lactic-co-glycolic-acid (PLGA) nanoparticles (NPs) for chemotherapy and Fe3O4 magnetic NPs (MNPs) for active targeting using an electromagnetic actuation (EMA) system. And, the macrophage-based microrobots are synthesized through the phagocytosis of the drug NPs and MNPs in the macrophages. The anticancer effects of the microrobots on tumor cell lines (CT-26 and 4T1) are evaluated in vitro by cytotoxic assay. In addition, the active tumor targeting by the EMA system and macrophage recruitment, and the chemotherapeutic effect of the microrobots are evaluated using three-dimensional (3D) tumor spheroids. The microrobots exhibited clear cytotoxicity toward tumor cells, with a low survivability rate (<50%). The 3D tumor spheroid assay showed that the microrobots demonstrated hybrid actuation through active tumor targeting by the EMA system and infiltration into the tumor spheroid by macrophage recruitment, resulting in tumor cell death caused by the delivered antitumor drug. Thus, the active, transportable, macrophage-based theragnostic microrobots can be considered to be biocompatible vectors for cancer therapy.

Guidance and Self‐Sorting of Active Swimmers: 3D Periodic Arrays Increase Persistence Length of Human Sperm Selecting for the Fittest

“…Moreover, the similarities in fluid physics of swimmers across different species,46 from bacteria to parasites, make these findings broadly applicable to other motile microorganisms. In fact, many such active swimmers across diverse biological systems have been an inspiration for the design of artificial micrometer‐scale flagellar systems including biohybrid microrobots,47, 48, 49, 50, 51, 52 and we also envision broad applications of our findings in areas such as medical diagnosis,53 biosensing,54 and targeted drug delivery 55…”

Tumor microenvironment complexity and therapeutic implications at a glance

“…TAM depletion by induction of selective activation of apoptosis pathways in TAM by agents such as alendronateglucomannan conjugate [102] and TAM re-education to convert macrophage to M1 phenotype [101], as well as use of TAM as carrier for selective drug delivery to cancer cells are additional therapeutic tactics [10,111,112].…”

Progress in tumor-associated macrophage (TAM)-targeted therapeutics

“…A study by Chang and Guo et al shows that the size of nanoparticles internalized by macrophages can significantly alter locomotivity of the macrophages, with smaller nanoparticles (30 and 50 nm) having higher uptake into macrophages than larger nanoparticles (100 and 500 nm) but also more readily retarding the migration rate of the macrophages; this study suggests that 100 nm nanoparticles provide a good balance for effective drug loading and macrophage migration [174]. To increase control over drug activity from macrophage carriers, macrophage have been loaded with temperature-responsive liposomes for triggered release [216], with gold-silica nanoshells for photothermal therapy [215], and with iron oxide nanoparticles for dual tracking and trafficking using electromagnetic actuation [214][222][223]. …”