A Self-Driven Bioreactor Based on Bacterium–Metal–Organic Framework Biohybrids for Boosting Chemotherapy via Cyclic Lactate Catabolism

Abstract

The excessive lactate in the tumor microenvironment always leads to poor therapeutic outcomes of chemotherapy. In this study, a self-driven bioreactor (defined as SO@MDH, where SO is Shewanella oneidensis MR-1 and MDH is MIL-101 metal–organic framework nanoparticles/doxorubicin/hyaluronic acid) is rationally constructed via the integration of doxorubicin (DOX)-loaded metal–organic framework (MOF) MIL-101 nanoparticles with SO to sensitize chemotherapy. Owing to the intrinsic tumor tropism and electron-driven respiration of SO, the biohybrid SO@MDH could actively target and colonize hypoxic and eutrophic tumor regions and anaerobically metabolize lactate accompanied by the transfer of electrons to Fe3+, which is the key component of the MIL-101 nanoparticles. As a result, the intratumoral lactate would undergo continuous catabolism coupled with the reduction of Fe3+ to Fe2+ and the subsequent degradation of MIL-101 frameworks, leading to an expeditious drug release for effective chemotherapy. Meanwhile, the generated Fe2+ will be promptly oxidized by the abundant hydrogen peroxide in the tumor microenvironment to reproduce Fe3+, which is, in turn, beneficial to circularly catabolize lactate and boost chemotherapy. More importantly, the consumption of intratumoral lactic acid could significantly inhibit the expression of multidrug resistance-related ABCB1 protein (also named P-glycoprotein (P-gp)) for conquering drug-resistant tumors. SO@MDH demonstrated here holds high tumor specificity and promising chemotherapeutic efficacy for suppressing tumor growth and overcoming multidrug resistance, confirming its potential prospects in cancer therapy.

Growth of Cu2O Nanoparticles on Two-Dimensional Zr–Ferrocene–Metal–Organic Framework Nanosheets for Photothermally Enhanced Chemodynamic Antibacterial Therapy

“…Bacterial infection is a severe threat to human health all over the world. , Because of the uncontrolled use of antibiotics for a long time, many bacteria have developed drug resistance, which will seriously threaten human health. , Therefore, there is a pressing need to design and develop new antimicrobial platforms to meet the needs of human beings. , In recent years, some antibacterial therapies without using antibiotics have been developed such as the controlled release of silver ions, , photothermal therapy (PTT), , chemodynamic therapy (CDT), − and photodynamic therapy (PDT). , Among them, CDT is a treatment that requires no extra energy input, and thus, it can avoid the limitation of light penetration in tissues . In the last decade, many inorganic nanomaterials, such as metal oxides ,, and metal chalcogenides, − have been developed as nanoagents for antibacterial through CDT because they can catalyze the Fenton or Fenton-like reaction with hydrogen peroxide to generate highly toxic hydroxyl radicals (·OH) to destroy biomolecules (such as DNA and proteins) in bacteria.…”

“…1,2 Because of the uncontrolled use of antibiotics for a long time, many bacteria have developed drug resistance, which will seriously threaten human health. 3,4 Therefore, there is a pressing need to design and develop new antimicrobial platforms to meet the needs of human beings. 5,6 In recent years, some antibacterial therapies without using antibiotics have been developed such as the controlled release of silver ions, 7,8 photothermal therapy (PTT), 9,10 chemodynamic therapy (CDT), 11−15 and photodynamic therapy (PDT).…”

Recent advances in anti-multidrug resistance for nano-drug delivery system

“…In addition, among cyclic lactate catabolism, lactate dehydrogenase A (LDHA) can promote the tumor cells chemotherapy resistance. An intelligent bioreactor was tailor-made by the integration of metal-organic framework (MOF) with nonpathogenic Shewanella oneidensis MR-1 (SO), and the lactic acid catabolism consumed by SO and MOF could suppress the P-gp expression which could effectively conquer drug-resistant tumors (Wang et al., 2021c ). Considering the let-7 family negatively regulating proto-oncogenes, cyanine5 (Cy5)-modified miRNA (let-7i) and platinum were integrated into nanographene oxide for reversing drug resistance via suppressing the cyclin D1 protein (Yan et al., 2022 ).…”

Perspectives of metal-organic framework nanosystem to overcome tumor drug resistance

“…This DDS was delivered to cancer cells with CD44 overexpression owing to the targeting ability of HA towards CD44, and then released Zr (IV)-based porphyrinic MOF and CHC for enhanced photodynamic therapy (PDT) effect. Du et al synthesized DOX@NH 2 -MIL-88B-COD@CS NPs, which were loaded with cholesterol oxidase (COD), DOX, and chondroitin sulfate (CS) gel shell [39] . The COD catalyzed the degradation of cholesterol on the cell membrane to weaken the bio-barrier of cell membrane, thus facilitating the delivery of NPs into the cell.…”