Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Feb 4;9(1):7.
doi: 10.1186/s40580-022-00297-8.

Bioenzyme-based nanomedicines for enhanced cancer therapy

Mengbin Ding #  1 , Yijing Zhang #  1 , Jingchao Li  2 , Kanyi Pu  3
Affiliations
Review

Bioenzyme-based nanomedicines for enhanced cancer therapy

Mengbin Ding et al. Nano Converg. .

Abstract

Bioenzymes that catalyze reactions within living systems show a great promise for cancer therapy, particularly when they are integrated with nanoparticles to improve their accumulation into tumor sites. Nanomedicines can deliver toxic bioenzymes into cancer cells to directly cause their death for cancer treatment. By modulating the tumor microenvironment, such as pH, glucose concentration, hypoxia, redox levels and heat shock protein expression, bioenzyme-based nanomedicines play crucial roles in improving the therapeutic efficacy of treatments. Moreover, bioenzyme-mediated degradation of the major components in tumor extracellular matrix greatly increases the penetration and retention of nanoparticles in deep tumors and infiltration of immune cells into tumor tissues, thus enhancing the efficacies of chemotherapy, phototherapy and immunotherapy. In this review, we summarize the recent progresses of bioenzyme-based nanomedicines for enhanced cancer therapy. The design and working mechanisms of the bioenzyme-based nanomedicines to achieve enhanced chemotherapy, photothermal therapy, photodynamic therapy, chemodynamic therapy, radiotherapy and immunotherapy are introduced in detail. At the end of this review, a conclusion and current challenges and perspectives in this field are given.

Keywords: Cancer therapy; Drug delivery system; Enzyme; Nanomedicine; Tumor microenvironment.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Summary of bioenzyme-based nanomedicines for enhanced cancer therapy via degradation of extracellular matrix, induction of cell apoptosis, regulation of tumor microenvironment, and activation of immune responses
Fig. 2
Fig. 2
a Schematic illustration of the intracellular co-delivery of RNase A and DOX using a multistage cooperative drug delivery nanoplatform formed by mPEG-b-PGCA-b-PGTA for combination cancer therapy. b Tumor volume changes of B16F10-tumor-bearing mice after intravenous injection of PBS, NP-RNBC, NP-DOX, DOX, and NP-DOX-RNBC on day 0, 3, 6, and 9. c Relative tumor volume of the mice treated as described in (b) on day 14. Inset: Representative photographs of the excised tumors from the mice treated as described in (b) on day 14. Reproduced with permission from [39]. Copyright 2020, Wiley–VCH
Fig. 3
Fig. 3
a Schematic illustration of the fabrication of collagenase-based nanoscavengers and their size increase and dissociation of the collagenase containing components in response to the acidic pH. b Schematic illustration of the increased penetration and retention of nanoparticles in deep tumor tissues via the combined action of collagenase digestion of collagen fibers and particle size increase, and the destruction of mitochondrial DNA via mitochondria-specific targeting and release of cisplatin drugs into mitochondria. Reproduced with permission from [45]. Copyright 2020, Wiley–VCH
Fig. 4
Fig. 4
a Chemical structures of PCB1 and PCB2 and schematic for the synthesis of PCB-Bro. b Immunofluorescence collagen I staining images of 4T1 tumors after intratumoral injection of saline, PCB1, or PCB1-Bro with or without laser irradiation. Cell nucleus were stained by 4′,6-diamidino-2-phenylindole (DAPI) and collagen I was stained by Alexa Fluor 488 conjugated anti-collagen I antibody. c Illustration of photothermally triggered enzyme activation of PCB1-Bro towards collagen digestion for enhanced accumulation of nanoparticles in tumors. d Tumor growth curves of 4T1 tumor-bearing mice in different groups. Reproduced with permission from [59]. Copyright 2018, Wiley–VCH
Fig. 5
Fig. 5
a Illustration of the proposed mechanism for the photoactivated synergistic therapeutic action of organic semiconducting polymer pro-nanoenzyme (OSPE) including PDT and intracellular RNA degradation. b Schematic illustration of OSPE-mediated complete inhibition of tumor growth and metastasis. c The tumor growth curves in 4T1 tumor-bearing mice. d Histological hematoxylin and eosin staining of pulmonary metastatic tumors in 4T1 tumor-bearing mice. Tumors were indicated by the black dashed curves. e Quantitative analysis of pulmonary metastatic nodules in different treatment groups. Reproduced with permission from [77]. Copyright 2019, American Chemical Society
Fig. 6
Fig. 6
a The synthetic procedures of hybrid enzyme nanogel (FIGs-LC) include: (1) self-assembly of Fe3O4 nanoparticles-encapsulated polystyrene-block-poly (acrylic acid) (PS-b-PAA) micelles (Fe3O4@PS-b-PAA) in selective solution; (2) the formation of ICG-loaded hybrid nanoparticles (Fe3O4@IHPs) by doping ICG and introducing organic silane 3-mercaptopropyltrimethoxysilane (MPTMS); (3) acid phosphatase (AP)-triggered hydrogel coating onto Fe3O4@IHPs, denoted with Fe3O4@IHPs nanogels (FIGs); (4) immobilization of LOx and CAT into FIGs, the final particles are denoted by FIGs-LC. b Schematic circuit diagram for the peroxisome-inspired therapeutic mechanism of FIGs-LC based on the dual-enzyme-regulated ROS generation with GSH and NIR activation: the intratumoral lactate and H2O2 are catalyzed by LOx and CAT (resistor regulation) to generate H2O2 and O2, respectively. Then, H2O2 is used to produce·OH (current I1) in the presence of Fe3O4 nanoparticles within GSH-enriched acidic tumor microenvironment (Switch-1, S1), leading to the cancer cell death (bulb on). In the reaction, the produced O2 is converted into 1O2 (current I2) under the irradiation of an 808 nm laser (Switch-2, S2), which can also cause significant cell death (bulb on). Both CDT and PDT can be executed independently and induce the death of cancer cells, as well be activated simultaneously (S1 and S2 are connected) to achieve improved antitumor therapy. c Change in relative tumor volume during the treatment. d Average weight of excised tumors from the tumor-bearing mice after 21 days of treatment. Reproduced with permission from [82]. Copyright 2021, Springer Nature
Fig. 7
Fig. 7
a A scheme showing the preparation of CAT@Pt(IV)-liposomes for tumor hypoxia relieved cancer chemo-RT. b Ex vivo immunofluorescence staining of tumor slices collected from mice with intravenous injection of saline, Pt(IV)-liposomes, CAT@liposomes, or CAT@Pt(IV)-liposomes at 24 h. c Tumor growth curves of mice after various different treatments indicated. Reproduced with permission from [87]. Copyright 2017, Elsevier
Fig. 8
Fig. 8
a Schematic illustration of the preparation procedure of SPNK. b The proposed mechanism of SPNK-mediated synergistic photodynamic immunometabolic therapy. Growth curves of c primary tumors and d distant tumors in B16F10 tumor-bearing mice after different treatments. e Survival curves for the treated and control mice. Reproduced with permission from [99]. Copyright 2021, Wiley–VCH
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Wu Q, He Z, Wang X, Zhang Q, Wei Q, Ma S, Ma C, Li J, Wang Q. Nat. Commun. 2019;10:240. - PMC - PubMed
    1. Lian X, Huang Y, Zhu Y, Fang Y, Zhao R, Joseph E, Li J, Pellois JP, Zhou HC. Angew. Chem. Int. Ed. 2018;57:5725–5730. - PMC - PubMed
    1. Jin S, Weng L, Li Z, Yang Z, Zhu L, Shi J, Tang W, Ma W, Zong H, Jiang W. J. Mater. Chem. B. 2020;8:4620–4626. - PubMed
    1. Zhou J, Wang M, Ying H, Su D, Zhang H, Lu G, Chen J. ACS Biomater. Sci. Eng. 2018;4:2404–2411. - PubMed
    1. Si X, Song W, Yang S, Ma L, Yang C, Tang Z. Macromol. Biosci. 2019;19:1900148. - PubMed

LinkOut - more resources