https://pubs.rsc.org/en/content/articlepdf/2021/CC/D1CC05157A

Metal-organic frameworks (MOFs) as host materials for the enhanced delivery of biomacromolecular therapeutics.

State of the Art Advancements in Sonodynamic Therapy (SDT): Metal-Organic Frameworks for SDT

MnMOF-based Microwave-glutathione Dual-responsive Nano-missile for Enhanced Microwave Thermo-dynamic Chemotherapy of Drug-resistant Tumors

Wearable, point-of-care diagnostics, and biosensors are on the verge of bringing transformative changes in detection, management, and treatment of cancer. Bioinspired materials with new forms and functions have frequently been used, in both translational and commercial spaces, to fabricate such diagnostic platforms. Engineered from organic or inorganic molecules, bioinspired systems are naturally equipped with biorecognition and stimuli-sensitive properties. Mechanisms of action of bioinspired materials are deeply connected with thermodynamically or kinetically controlled self-assembly at the molecular and supramolecular levels. Thus, integration of bioinspired materials into wearable devices, either as triggers or sensors, brings about unique device properties usable for detection, capture, or rapid readout for an analyte of interest. In this review, we present the basic principles and mechanisms of action of diagnostic devices engineered from bioinspired materials, describe current advances, and discuss future trends of the field, particularly in the context of cancer.

Bioinspired Materials for Wearable Devices and Point-of-Care Testing of Cancer.

Lung cancer is one of the fatal cancers worldwide, and over 60% of patients are lung adenocarcinoma (LUAD). Our clinical data demonstrated that DNA methylation of the promoter region of miR-126-3p was upregulated, which led to the decreased expression of miR-126-3p in 67 cases of lung cancer tissues, implying that miR-126-3p acted as a tumor suppressor. Transduction of miR-126-3p is a potential therapeutic strategy for treating LUAD, yet the physiological environment and properties of miRNA challenge current transduction approaches.We evaluated the expression of miR-126-3p in 67 pairs of lung cancer tissues and the corresponding adjacent non-tumorous tissues by Reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The relationship between the overall survival of lung cancer patients and miR-126-3p was analyzed by the Cancer Genome Atlas cohort database (Oncolnc, http://www.oncolnc.org ). We analyzed DNA methylation Methylation-specific PCR (MSP) analysis. To determine whether ADAM9 is the direct target of miR-126-3p, we performed the 3'-UTR luciferase reporter assay. The protein levels in the cells or tissues were evaluated with western blotting (WB) analysis. The biodistribution of nanoparticles were monitored by in vivo tracking system.We describe the development of novel stealth and matrix metalloproteinase 2 (MMP2)-activated biomimetic nanoparticles, which are constructed using MMP2-responsive peptides to bind the miR-126-3p (known as MAIN), and further camouflaged with red blood cell (RBC) membranes (hence named REMAIN). REMAIN was able to effectively transduce miRNA into lung cancer cells and release them via MMP2 responsiveness. Additionally, REMAIN possessed the advantages of the natural RBC membrane, including extended circulation time, lower toxicity, better biocompatibility, and immune escape. Moreover, in vitro and in vivo results demonstrated that REMAIN effectively induced apoptosis of lung cancer cells and inhibited LUAD development and progression by targeting ADAM9.The novel style of stealth and MMP2-activated biomimetic nanoparticles show great potential in miRNA delivery. 

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The reversion of DNA methylation-induced miRNA silence via biomimetic nanoparticles-mediated gene delivery for efficient lung adenocarcinoma therapy

Bioinspired metal–organic frameworks mediated efficient delivery of siRNA for cancer therapy

Apigenin suppresses tumor angiogenesis and growth via inhibiting HIF-1α expression in non-small cell lung carcinoma.

Recent evidence has indicated that overexpression of the epigenetic reader bromodomain‐containing protein 4 (BRD4) contributes to a poor prognosis of lung cancers, and the suppression of its expression promotes cell apoptosis and leads to tumor shrinkage. Proteolysis targeting chimera (PROTAC) has recently emerged as a promising therapeutic strategy with the capability to precisely degrade targeted proteins. Herein, a novel style of versatile nano‐PROTAC (CREATE (CRV‐LLC membrane/DS‐PLGA/dBET6)) is developed, which is constructed by using a pH/GSH (glutathione)‐responsive polymer (disulfide bond‐linked poly(lactic‐co‐glycolic acid), DS‐PLGA) to load BRD4‐targeted PROTAC (dBET6), followed by the camouflage with engineered lung cancer cell membranes with dual targeting capability. Notably, CREATE remarkably confers simultaneous targeting ability to lung cancer cells and tumor‐associated macrophages (TAMs). The pH/GSH‐responsive design improves the release of dBET6 payload from nanoparticles to induce pronounced apoptosis of both cells, which synergistically inhibits tumor growth in both subcutaneous and orthotopic tumor‐bearing mouse model. Furthermore, the efficient tumor inhibition is due to the direct elimination of lung cancer cells and TAMs, which remodels the tumor microenvironment. Taken together, the results elucidate the construction of a versatile nano‐PROTAC enables to eliminate both lung cancer cells and TAMs, which opens a new avenue for efficient lung cancer therapy via PROTAC.

Versatile Nano‐PROTAC‐Induced Epigenetic Reader Degradation for Efficient Lung Cancer Therapy

Abstract Aggregation-induced emission luminogens (AIEgens) have emerged as novel phototherapeutic agents with high photostability and excellent performance to induce photodynamic and/or photothermal effects. In this study, a zwitterion-type NIR AIEgens C 41 H 37 N 2 O 3 S 2 (named BITT) with biomimetic modification was utilized for lung cancer therapy. The tumor-associated macrophage (TAM)-specific peptide (CRV) was engineered into the lung cancer cell-derived exosomes. The CRV-engineered exosome membranes (CRV-EM) were obtained to camouflage the BITT nanoparticles (CEB), which targeted both lung cancer cells and TAMs through homotypic targeting and TAM-specific peptide, respectively. The camouflage with CRV-EM ameliorated the surface function of BITT nanoparticles, which facilitated the cellular uptake in both cell lines and induced significant cell death in the presence of laser irradiations in vitro and in vivo. CEB showed improved circulation lifetime and accumulations in the tumor tissues in vivo, which induced efficient photodynamic and photothermal therapy. In addition, CEB induced the tumor microenvironment remodeling as indicated by the increase of CD8 + and CD4 + T cells, as well as a decrease of M2 TAM and Myeloid-derived suppressor cells (MDSCs). Our work developed a novel style of bioinspired AIE aggregates, which could eliminate both lung cancer cells and TAMs, and remodel the tumor environments to achieve an efficient lung cancer therapy. To the best of our knowledge, we are the first to use this style of bioinspired AIE aggregates for photo-mediated immunotherapy in lung cancer therapy. 

/pdf/two-birds-with-one-stone-strategy-for-the-lung-cancer-1p4t7ge4.pdf

Mengmeng Yi

Papers

Bioinspired metal–organic frameworks mediated efficient delivery of siRNA for cancer therapy

Apigenin suppresses tumor angiogenesis and growth via inhibiting HIF-1α expression in non-small cell lung carcinoma.

Versatile Nano‐PROTAC‐Induced Epigenetic Reader Degradation for Efficient Lung Cancer Therapy

“Two birds with one stone” strategy for the lung cancer therapy with bioinspired AIE aggregates