Tailoring cell-inspired biomaterials to fuel cancer therapy

Abstract

Cancer stands as a predominant cause of mortality across the globe. Traditional cancer treatments, including surgery, radiotherapy, and chemotherapy, are effective yet face challenges like normal tissue damage, complications, and drug resistance. Biomaterials, with their advantages of high efficacy, targeting, and spatiotemporal controllability, have been widely used in cancer treatment. However, the biocompatibility limitations of traditional synthetic materials have restricted their clinical translation and application. Natural cell-inspired biomaterials inherently possess the targeting abilities of cells, biocompatibility, and immune evasion capabilities. Therefore, cell-inspired biomaterials can be used alone or in combination with other drugs or treatment strategies for cancer therapy. In this review, we first introduce the timeline of key milestones in cell-inspired biomaterials for cancer therapy. Then, we describe the abnormalities in cancer including biophysics, cellular biology, and molecular biology aspects. Afterwards, we summarize the design strategies of cell-inspired antitumor biomaterials. Subsequently, we elaborate on the application of antitumor biomaterials inspired by various cell types. Finally, we explore the current challenges and prospects of cell-inspired antitumor materials. This review aims to provide new opportunities and references for the development of antitumor cell-inspired biomaterials.

Keywords: Biomaterials; Cancer therapy; Cell-inspired.

Graphical abstract

Fig. 1

Timeline of key milestones in cell-inspired biomaterials for cancer therapy, which include science advances, approval products, and clinical trials.

Fig. 2

Illustration of the material design and action mechanism of cell-inspired anti-cancer biomaterials, which include living-cell based drug delivery system, engineered cells, biomimetic cell biomaterials, and cell-derived vesicle delivery system.

Fig. 3

Tumor abnormalities in biophysics, cell, biochemistry, and molecular biology. Understanding the heterogeneity of the tumor microenvironment is beneficial for improving the design of anti-tumor biomaterials.

Fig. 4

Schematic of DOX@PLT-IL-15 engineered via one-step fusion. (A). Illustration depicting the synthesis of DOX@PLT-IL-15 and its impact on combating tumor metastasis and postoperative recurrence, as well as stimulating the immune response. (B). In vivo tumor bioluminescence images of postoperative mice receiving different treatments [70]. © 2024 Wiley-VCH GmbH.

Fig. 5

Schematic depiction of an engineered, endogenous TAM-targeting biomimetic nano-RBC platform designed to enhance cancer chemoimmunotherapy through TIME reprogramming. (A). The schematic representation showcases the construction of the DOX-loaded biomimetic nano-RBC system (V(Hb)@DOX). (B). Illustration of the mechanism by which the endogenously targeted V(Hb)@DOX NPs interact with TAMs, leading to improved chemo-immunotherapeutic outcomes via TIME modulation. (C). Curves of tumor growth following administration of different treatments. (D). The mean tumor weight was harvested from mice on day 27 following the initiation of the respective treatment regimens. (E). Illustrative pulmonary metastatic nodules (indicated by arrow) in mice upon completion of the treatment regimen. (F). The mean count of pulmonary metastatic nodules observed after the treatment period. (G). Growth curves of recurrent tumors 25 days following surgical excision of the original tumors [99]. © 2021 Wiley‐VCH GmbH.

Fig. 6

(A). Representation of the synthesis process for EV@RGT and the mechanism of its anticancer action. (B). Images of excised tumors from euthanized mice captured on the 15th day post-treatment. (C). Growth trajectories of tumor volume in mice subjected to various treatments. (D). Body weight changes in mice subjected to various treatments [105]. Copyright © 2023, American Chemical Society.

Fig. 7

(A). Representation of the hybrid nanovesicles comprising bispecific CAR T cell-derived exosomes and liposomes for the treatment of lung cancer. (B). Bioluminescence and tumor growth on days 0, 7, and 14 of treatment. (C). Representative lung images from tumor-bearing mice across different treatment groups. (D). Survival curves and (E). body weight changes of tumor-bearing mice in various treatment groups [129]. Copyright © 2023, American Chemical Society.

Fig. 8

(A). Illustration of the Injectable iCS-HAp A/B-NK Complex Schema [130]. Copyright © 2024, American Chemical Society (B). DNA frameworks are engineered on cellular surfaces to enable precise and controlled attachment of proteins. (C). The NK cells modified with sialidase effectively overcome the inhibitory effects of sialic acids at the tumor-NK cell interface, thereby amplifying the immune response [117]. Copyright © 2023, American Chemical Society.

Fig. 9

(A). Diagram showing TNBC cells loaded with PD-1 and DOX for a combined chemo-immunotherapy approach targeting lung metastasis. (B). Illustrative images of lungs from each group, with metastatic lesions indicated by white arrows. (C). Typical bioluminescent scans show metastatic lung lesions across the groups [145]. © 2022 Wiley‐VCH GmbH.

Fig. 10

Perspectives of cell-inspired biomaterials for cancer therapy. Presently, cell-inspired biomaterials for cancer therapy have made obvious progress. Looking to the future, it's recommended to 1) explore new aspects of biomaterial synthesis and delivery systems; 2) understand the complex interactions between cell-inspired biomaterials and tumor cells; 3) develop potential technologies to tailor cells for antitumor therapy; 4) screen new targets; 5) facilitate clinical transformation.