Bioinspired micro- and nanostructured systems for cancer therapy

Abstract

Numerous organisms in nature have demonstrated enhanced biocompatibility, precise tumor targeting capabilities, and efficient tissue traversal within the human body. Drawing inspiration from these organisms, researchers have employed bioengineering, bioconjugation, and micro- or nanotechnology to fabricate bioinspired micro- and nanostructured systems. These systems play a crucial role in addressing the limitations of conventional anticancer drugs and nanomaterials concerning biocompatibility, effective penetration of physiological barriers, as well as selective tumor targeting, thereby leading to improved therapeutic efficacy while minimizing nonspecific adverse effects on healthy cells. Consequently, extensive exploration of these bioinspired micro- and nanostructured systems has been undertaken across various cancer treatment modalities with some progressing into preclinical or clinical stages. However, our understanding of this field remains limited which may impede research progress, clinical translation efforts, and practical applications. Therefore, this study presents a systematic classification of bioinspired micro- and nanostructured systems for cancer therapy that comprehensively elucidates their sources of inspiration and design principles. Furthermore, it extensively discusses the current status of clinical translation efforts while identifying prevailing challenges and exploring future prospects. This work will establish a robust theoretical framework and serve as a valuable reference to facilitate advancements in research and clinical application within this field.

Keywords: biocompatibility; bioinspired micro‐ and nanostructured systems; cancer therapy; traverse physiological barriers.

FIGURE 1

A global comparison between traditional and bioinspired cancer therapies. The limitations of traditional cancer therapies include lack of efficiency to metastatic cancers and the existence of side effects. Bioinspired micro/nano systems may have better improvements on the aspects of histocompatibility, penetration, and targeting.

FIGURE 2

Global classification and applications of bioinspired micro‐ and nanostructured systems. The classification, subclassification, and applications of bioinspired micro‐ and nanostructured systems are presented with interconnected relationships.

FIGURE 3

Bidirectional designs and applications of bacteria based cancer therapy. (A) Schematic illustration of the engineered bacteria based ECM‐targeting and cancer therapy. (B) Measurements of HAase activity in engineered HAase‐expressing bacteria. (C) Representative noninvasive in vivo imaging of bacterial bioluminescence. (D) Graphs depicting changes in the tumor volume over time after injections with bacteria. (E) Schematic illustration of the tumor‐harbored bacteria based targeting and cancer therapy. (F) HAADF–STEM images of LTA–MSNs. (G) Targeting ability of LTA–MSNs to bacteria in a flow environment. (H) CT scanning of tumor‐bearing mice at 14 and 21 days of the treatment. (I) Survival curves after receiving various treatments. Panels B–D were reproduced from Ref. with permission from Elsevier (license number 5875820460360), Copyright 2023. Panels F–I were reprinted (adapted) with permission from Ref. . Copyright 2022 American Chemical Society. HAase, hyaluronidase; HA, hyaluronan; SLlux, Salmonella carrying an empty vector; SLHAas, plasmid pBAD–HAase was transformed into ΔppGpp S. typhimurium; SLlux/HAase, ΔppGpp S. typhimurium harboring the luciferase operon; Doxo, doxorubicin; LTA, lipoteichoic acid; MSN, mesoporous silica nanoparticle; IRT, irinotecan; BSA, bovine serum albumin; ABX, antibiotic cocktail.

FIGURE 4

Overview of cell types and their distinctive features in the context of cell hitchhiking. The classification, cellular structures, and characteristics of various cell types are presented separately from the inner layer to the outer layer.

FIGURE 5

Overview of the stages and current status of clinical translation. The upper part of the figure depicts the general processes involved in developing clinical therapies, ranging from basic research to various stages of clinical trials. Meanwhile, the lower part illustrates the latest status of recently registered clinical trials for bioinspired micro‐ and nanostructured systems applications.