A Bacteria-Inspired Morphology Genetic Biomedical Material: Self-Propelled Artificial Microbots for Metastatic Triple Negative Breast Cancer Treatment

Abstract

Morphology genetic biomedical materials (MGBMs), referring to fabricating materials by learning from the genetic morphologies and strategies of natural species, hold great potential for biomedical applications. Inspired by the cargo-carrying-bacterial therapy (microbots) for cancer treatment, a MGBM (artificial microbots, AMBs) was constructed. Rather than the inherent bacterial properties (cancerous chemotaxis, tumor invasion, cytotoxicity), AMBs also possessed ingenious nitric oxide (NO) generation strategy. Mimicking the bacterial construction, the hyaluronic acid (HA) polysaccharide was induced as a coating capsule of AMBs to achieve long circulation in blood and specific tissue preference (tumor tropism). Covered under the capsule-like polysaccharide was the combinatorial agent, the self-assembly constructed by the amphiphilic dendrons with abundant l-arginine residues peripherally (as endogenous NO donor) and hydrophobic chemotherapeutic drugs at the core stacking on the surface of SWNTs (the photothermal agent) for a robust chemo-photothermal therapy (chemo-PTT) and the elicited immune therapy. Subsequently, the classic inducible nitric oxide synthase (iNOS) pathway aroused by immune response was revolutionarily utilized to oxidize the l-arginine substrates for NO production, the process for which could also be promoted by the high reactive oxygen species level generated by chemo-PTT. The NO generated by AMBs was intended to regulate vasodilation and cause a dramatic invasion (as the microbots) to disperse the therapeutic agents throughout the solid tumor for a much more enhanced curative effect, which we defined as “self-propulsion”. The self-propelled AMBs exhibiting impressive primary tumor ablation, as well as the distant metastasis regression to conquer the metastatic triple negative breast cancer, provided pioneering potential therapeutic opportunities, and enlightened broad prospects in biomedical application.

Engineered Bacterial Biomimetic Vesicles Reprogram Tumor-Associated Macrophages and Remodel Tumor Microenvironment to Promote Innate and Adaptive Antitumor Immune Responses

“…15,91 It should be noted that the half-life of NO is only 4−6 s, so this direct tumor cell killing depends on close contact between macrophages and tumor cells. 18,92 In contrast, Arg-1, which is highly expressed in M2 macrophages, inhibits NO production through metabolizing L-Arg, a precursor for NO production, 91,93 to ornithine and polyamines. Besides the killing effects of NO and ROS, direct phagocytosis by activated macrophages is another important mechanism for the clearance of tumor cells.…”

Development of organic photosensitizers for antimicrobial photodynamic therapy

“…), as a new therapeutic mode, has aroused widespread attention because it does not produce drug resistance and plays a key role as an influential endogenous signaling molecule in a variety of biological processes. [65][66][67][68] Inspired by the favorable antimicrobial and biofilm-abating properties of gas therapy, numerous studies have combined gas therapy with PDT to achieve better efficacy. Cai's group reported a novel PDT-driven NO-controllable release system (Ce6@Arg-ADP), which was built using an L-Arg-rich amphiphilic dendritic peptide (Arg-ADP) as a carrier and loaded with Ce6 (Fig.…”

Microbiota in Tumors: From Understanding to Application

“…[ 130 , 131 , 132 , 133 , 134 ] Furthermore, some researchers have developed novel drug delivery systems using outer membrane vesicles or artificial microbots. [ 135 , 136 ] Recently, a group of researchers designed an engineered E. coli that increased the concentration of L‐arginine and T cell infiltration in TMEs, thereby improving the anti‐tumor effect. [ 137 ] Together, therapies based on microorganisms have attracted a lot of attention and some drugs have entered the clinical stage as shown in Table 2 .…”