The integration of reactive oxygen species (ROS)-involved photodynamic therapy (PDT) and chemodynamic therapy (CDT) holds great promise for enhanced anticancer effects. Herein, we report biodegradable cancer cell membrane-coated mesoporous copper/manganese silicate nanospheres (mCMSNs) with homotypic targeting ability to the cancer cell lines and enhanced ROS generation through singlet oxygen ( 1 O 2 ) production and glutathione (GSH)-activated Fenton reaction, showing excellent CDT/PDT synergistic therapeutic effects. We demonstrate that mCMSNs are able to relieve the tumor hypoxia microenvironment by catalytic decomposition of endogenous H 2 O 2 to O 2 and further react with O 2 to produce toxic 1 O 2 with a 635 nm laser irradiation. GSH-triggered mCMSNs biodegradation can simultaneously generate Fenton-like Cu + and Mn 2+ ions and deplete GSH for efficient hydroxyl radical (•OH) production. The specific recognition and homotypic targeting ability to the cancer cells were also revealed. Notably, relieving hypoxia and GSH depletion disrupts the tumor microenvironment (TME) and cellular antioxidant defense system, achieving exceptional cancertargeting therapeutic effects in vitro and in vivo. The cancer cells growth was significantly inhibited. Moreover, the released Mn 2+ can also act as an advanced contrast agent for cancer magnetic resonance imaging (MRI). Thus, together with photosensitizers, Fenton agent provider and MRI contrast effects along with the modulating of the TME allow mCMSNs to realize MRI-monitored enhanced CDT/PDT synergistic therapy. It provides a paradigm to rationally design TMEresponsive and ROS-involved therapeutic strategies based on a single polymetallic silicate nanomaterial with enhanced anticancer effects.

Cellular-membrane-coated nanoparticles have increasingly been pursued to leverage the natural cell functions for enhancing biocompatibility and improved therapeutic efficacy. Taking advantage of specialized cell membranes or combining functions from different membrane types facilitates the strengthening of their functionality. Herein, we fuse membrane materials derived from red blood cells (RBCs) and melanoma cells (B16-F10 cells) to create a hybrid biomimetic coating (RBC-B16), and RBC-B16 hybrid membrane camouflaged doxorubicin (DOX)-loaded hollow copper sulfide nanoparticles (DCuS@[RBC-B16] NPs) are fabricated for combination therapy of melanoma. The DCuS@[RBC-B16] NPs are comprehensively characterized, showing the inherent properties of the both source cells. Compared to the bare CuS NPs, the DCuS@[RBC-B16] NPs exhibit highly specific self-recognition to the source cell line in vitro and achieve markedly prolonged circulation lifetime and enhanced homogeneous targeting abilities in vivo inherited from the source cells. Thus, the DOX-loaded [RBC-B16]-coated CuS NP platform exhibits excellent synergistic photothermal/chemotherapy with about 100% melanoma tumor growth inhibition rate. The reported strategy may contribute to personalized nanomedicine of various tumors by combining the RBCs with a homotypic cancer membrane accordingly on the surface of the nanoparticle.

Tumor exosomes that inherit molecular markers from their parent cells are emerging as cellular "surrogates" in cancer diagnostics. Molecular profiling and detection of exosomes offer a noninvasive access to the state of cancer progression, yet are still technically challenging. Here we report an exosome-oriented, aptamer nanoprobe-based profiling (ExoAPP) assay to phenotype surface proteins and quantify cancerous exosomes in a facile mix-and-detect format. Our ExoAPP interfaces graphene oxide (GO) with target-responsive aptamers to profile exosomal markers across five cell types by complementing with enzymeassisted exosome recycling, revealing a heterogeneous pattern.This assay achieves a detection limit down to 1.6 × 10 5 particles/ mL, lowered by several orders of magnitude over other homogeneous protocols. Such a sensitive ExoAPP assay allows for monitoring epithelial-mesenchymal transition through heterogeneous exosomes without involving cellular internalization that often occurs in GO-based cargo delivery. Using ExoAPP to analyze blood samples from prostate cancer patients, we find that target exosome can be identified by surface PSMA, suggesting their potential in clinical diagnosis.

Exosomes are small membrane-bound nanovesicles with a size of 50−150 nm which contain many functional biomolecules, such as nucleic acids and proteins. Due to their high homology with parental generation, they are of great significance in clinical diagnosis. At present, the quantitative detection of low concentrations of cancer-derived exosomes present in biofluids is still a great challenge. In this study, we develop an electrical and label-free method to directly detect exosomes with high sensitivity based on a reduced graphene oxide (RGO) field effect transistor (FET) biosensor. An RGO FET biosensor modified with specific antibody CD63 in the sensing area was fabricated and was used for electrical and label-free quantification of exosomes. The method achieved a low limit of detection down to 33 particles/μL, which is lower than that of many other available methods. In addition, the FET biosensor was employed to detect exosomes in clinical serum samples, showing significant differences in detecting healthy people and prostate cancer (PCa) patients. Different from other technologies, this study provides a unique technology capable of directly quantifying exosomes without labeling, indicating its potential as a tool for early diagnosis of cancer.

Nucleic acids have been actively exploited to develop various exquisite nanostructures due to their unparalleled programmability. Especially, framework nucleic acids (FNAs) with tailorable functionality and precise addressability hold great promise for biomedical applications. In this review, we summarize recent progress of FNA-enabled biosensing in homogeneous solutions, on heterogeneous surfaces, and inside cells. We describe the strategies to translate the structural order and rigidity of FNAs to interfacial engineering with high controllability, and approaches to realize multiplexing for highly parallel in vitro detection. We also envision the marriage of the currently available FNA tool sets with other emerging technologies to develop a new generation of biosensors for precision diagnosis and bioimaging.