Magnetic‐Powered Janus Cell Robots Loaded with Oncolytic Adenovirus for Active and Targeted Virotherapy of Bladder Cancer

Abstract

for various fields, such as drug delivery, [1,2] biosensing, [3] detoxification, [4] and environmental remediation. [5] These miniaturized machines can convert local fuel or external energy (e.g., magnetic, ultrasound, or light) to driving force and obtain selfpropulsion in dynamic surroundings. [6] Due to the increasing demands and rigorous requirements of biomedical community, the composition of microrobots has been evolving from rigid and inorganic materials to functional and endogenous cells. [7] Incorporating natural cells with synthetic micromachines creates an elegant platform with synergistic properties of cell biofunctionalities and effective propulsion. The cargo-loading capability of cells is employed by cell-based microrobots to actively deliver drugs, [2,[8][9][10][11] such as red blood cell (RBC)based micromotors loaded with doxorubicin (DOX) and photosensitizer, [10,11] and neutrophil-based microrobots carrying paclitaxel (PTX). [2] However, the utilized chemotherapeutic agents in the robotic system are not specific to cancerous cells and occur drug leakage during transport, inducing unavoidable toxicity to normal regions along with limited therapeutic efficacy and undesired side effects. [12] Such compromised biosafety and antitumor index hinder the practical A unique robotic medical platform is designed by utilizing cell robots as the active "Trojan horse" of oncolytic adenovirus (OA), capable of tumor-selective binding and killing. The OA-loaded cell robots are fabricated by entirely modifying OA-infected 293T cells with cyclic arginine-glycine-aspartic acid tripeptide (cRGD) to specifically bind with bladder cancer cells, followed by asymmetric immobilization of Fe 3 O 4 nanoparticles (NPs) on the cell surface. OA can replicate in host cells and induce cytolysis to release the virus progeny to the surrounding tumor sites for sustainable infection and oncolysis. The asymmetric coating of magnetic NPs bestows the cell robots with effective movement in various media and wireless manipulation with directional migration in a microfluidic device and bladder mold under magnetic control, further enabling steerable movement and prolonged retention of cell robots in the mouse bladder. The biorecognition of cRGD and robust, controllable propulsion of cell robots work synergistically to greatly enhance their tissue penetration and anticancer efficacy in the 3D cancer spheroid and orthotopic mouse bladder tumor model. Overall, this study integrates cell-based microrobots with virotherapy to generate an attractive robotic system with tumor specificity, expanding the operation scope of cell robots in biomedical community.

Designing Intelligent Nanomaterials to Achieve Highly Sensitive Diagnoses and Multimodality Therapy of Bladder Cancer

“…They have several advantages, including a good chemical stability, excellent biocompatibility, passive targeting ability, large specific surface area, good thermal stability, high drug loading, and so on. [130] PLZ4@SeD [84] DOX-PS [85] SeDs [87] Thiolated MSN NPs [131] PAMAM-modified MSNPs [132] FA-TMLs@MNPs-GNRs-DOX [135] LP-gel [148] PLL-P(LP-co-LC) [149] Ur-PDA NC [154] NG/HCPT [155] OEGMA-PTX@Ce6 [156] SS CB GB [157] PEG-PAMAM NPs [160] IONP-HA@Gel [168] KP372-1 [86] Cy3-labeled 293T-R-Fe@OA [174] RT HSA-MnO 2 -CQ [92] CDT AgNPs [125] CONPs [133] nZnO [134] IT IR775@Met@Lip [96] MPDIα W [97] 522NP [98] AB680@EMVs-aPDL1 [99] PGFCS [100] CWS-NP [145] CWS-Nano-CL [146] CWS-FPL [147] Fe 3 O 4 @Chl/Fe CNPs [137] GT siRNA@CS-HAD [102] UMND [103] HNTs/siRNA [104] CRISPR-Cas13a/liposome systems [105] siNrf GCD [164] KDM6A-mRNA NPs [106] SCNTs/si-circPRMT5 [143] PTT Fe 3 O 4 @PDA-VCA-FA SPs [67] HAPO-1048 [112] BBTD+GA/PEG-RGD [113] Cu 2-X Se [128] HA-IR780 NP…”

“…The nanoplatform specifically combined with BC cells and through soluble tumor adenovirus (OA) replication in cancer cells induces lysis, achieves sustained infection and ablation of the tumor, and magnetic NPs in the magnetic coating allow directional migration of the nanoplatform platform, implement controlled movement in the bladder and prolong the residence time (Figure 15A,B). [174] Finally, monatomic catalysts have shown significantly different activity, selectivity and stability from conventional nanocatalysts due to their special structure, which has attracted increasing attention in various catalytic fields. Single atom catalytic materials (SACS) can provide a new method of tumor chemotherapy as a new nanocatalytic drug.…”

“…On the one hand, we reviewed some Reproduced with permission. [174] Copyright 2022, Wiley-VCH. With the continuous development of nanotechnology, an increasing number of studies have shown that nanotechnology has broad application prospects in improving the diagnostic effect of BC.…”

“…B) Motion speed and corresponding time-lapse images with trajectories (over 4 s) of cell robots under the RMF with different intensities and different frequencies. Reproduced with permission [174]. Copyright 2022, Wiley-VCH.…”

Recent Progress and Trends in X-ray-Induced Photodynamic Therapy with Low Radiation Doses

“…Notably, even without additional modifications on nanoscintillators, one foreseeable application of X-PDT for clinical translation is the treatment of orthotopic bladder cancer, considering the advantages of irrigation of nanomaterials into bladders directly before treatment and subsequent wash procedures would not induce severe or systematic cytotoxicity to patients. − The less sensitiveness of bladder tissues to low-dose X-ray irradiation could become another advantage to excite photosensitizers instead of the invasive endoscopic techniques of current conventional PDT. , …”