Cancer immunotherapy by silencing transcription factor c-Rel using peptide-based nanoparticles.

Background: Cancer immunotherapy has shown promising results in the clinic, but it faces great challenges such as low response rates and low efficacy in solid tumors. c-Rel, a member of the nuclear factor (NF)-κB family, is a newly described immune checkpoint for myeloid-derived suppressor cells (MDSCs), which contribute to the formation of immune-suppressive tumor microenvironment and resistance to cancer immunotherapy. How to selectively target myeloid c-Rel for the treatment of cancer is not well established.

Chemically engineered antibodies for autophagy-based receptor degradation.

Cell surface receptor-targeted protein degraders hold promise for drug discovery. However, their application is restricted because of the complexity of creating bifunctional degraders and the reliance on specific lysosome-shuttling receptors or E3 ubiquitin ligases. To address these limitations, we developed an autophagy-based plasma membrane protein degradation platform, which we term AUTABs (autophagy-inducing antibodies).

Programmable ultrasound-mediated swarms manipulation of bacteria-red blood cell microrobots for tumor-specific thrombosis and robust photothermal therapy.

Despite the excellent advantages of biomicrorobots, such as autonomous navigation and targeting actuation, effective penetration and retention to deep lesion sites for effective therapy remains a longstanding challenge. Here, we present dual-engine cell microrobots, which we refer to as PR-robots, created by conjugating photosynthetic bacteria (PSB) with red blood cells (RBCs). The robots penetrate the tumor interior in swarms through combined hypoxic traction and ultrasound actuation (UA).

Bioorthogonal oncolytic-virus nanovesicles combined bio-immunotherapy with CAR-T cells for solid tumors.

Various oncolytic viruses (OVs) have been adopted as therapeutic tools to increase the efficacy of chimeric antigen receptor (CAR)-T cells against solid tumors. However, the therapeutic effect of OVs has been limited by pre-existing neutralizing antibodies and poor targeting delivery for systemic administration. Herein, we propose using bioorthogonal OV nanovesicles to boost the antitumor effects of CAR-T cells in solid tumors by reshaping the tumor microenvironment.

Nanotherapeutic Approaches of Interleukin-3 to Clear the α-Synuclein Pathology in Mouse Models of Parkinson's Disease.

Astrocyte-microglia crosstalk is vital for neuronal survival and clearing aggregate accumulation in neurodegenerative diseases. While interleukin-3 (IL-3) has been reported to exert both protective and detrimental effects in neurodegenerative diseases, however, its role in α-synuclein pathology remains unclear. In this study, it is found that astrocytic IL-3 and microglial IL-3R are positively responsive to α-synuclein pathology in the brains of transgenic A53T Parkinson's disease (PD) mice and in an adeno-associated virus (AAV)-human α-synuclein (AAV-hα-Syn)-injected PD mouse model.

Astroglial membrane camouflaged Ptbp1 siRNA delivery hinders glutamate homeostasis via SDH/Nrf2 pathway.

Polypyrimidine tract-binding protein 1 (PTBP1) regulates numerous alternative splicing events during tumor progression and neurogenesis. Previously, PTBP1 downregulation was reported to convert astrocytes into functional neurons; however, how PTBP1 regulates astrocytic physiology remains unclear. In this study, we revealed that PTBP1 modulated glutamate uptake via ATP1a2, a member of Na/K-ATPases, and glutamate transporters in astrocytes.

Ultra-Sensitive Detection of the SARS-CoV-2 Nucleocapsid Protein via a Clustered Regularly Interspaced Short Palindromic Repeat/Cas12a-Mediated Immunoassay.

Tracking trace protein analytes in precision diagnostics is an ongoing challenge. Here, we developed an ultrasensitive detection method for the detection of SARS-CoV-2 nucleocapsid (N) protein by combining enzyme-linked immunosorbent assay (ELISA) with the clustered regularly interspaced short palindromic repeat/CRISPR-associated protein (CRISPR/Cas) system. First, the SARS-CoV-2 N protein bound by the capture antibody adsorbed on the well plate was sequentially coupled with the primary antibody, biotinylated secondary antibody, and streptavidin (SA), followed by biotin primer binding to SA.

Dynamic speckle illumination wide-field fluorescence microscopy with actively optical manipulation of rotational angles.

We present a dynamic speckle illumination wide-field fluorescence microscopy (DSIWFM) combined with a line optical tweezers (LOTs) for rotational fluorescence sectioning imaging. In this method, large polystyrene fluorescent microspheres are stably trapped with LOTs, and precisely manipulated to rotate around a specific rotation axis. During the rotation process, multiple raw fluorescence images of trapped microspheres are obtained with dynamic speckle illumination.

Light sheet fluorescence microscopy with active optical manipulation.

We present a light sheet fluorescence microscopy (LSFM) with active optical manipulation by using linear optical tweezers (LOTs). In this method, two coaxially transmitting laser beams of different wavelengths are shaped using cylindrical lenses to form a linear optical trapping perpendicular to the optical axis and an excitation light sheet (LS) parallel to the optical axis, respectively. Multiple large-sized polystyrene fluorescent microspheres are stably captured by LOTs, and their rotation angles around specific rotation axes are precisely controlled.

A mitochondria-targeting self-assembled carrier-free lonidamine nanodrug for redox-activated drug release to enhance cancer chemotherapy.

Mitochondria play a vital role in maintaining cellular homeostasis. In recent years, studies have found that mitochondria have an important role in the occurrence and development of tumors, and targeting mitochondria has become a new strategy for tumor treatment. Lonidamine (LND), as a hexokinase inhibitor, can block the energy supply and destroy mitochondria.

A Dual-Biomineralized Yeast Micro-/Nanorobot with Self-Driving Penetration for Gastritis Therapy and Motility Recovery.

Micro-/nanorobots have attracted great interest in the field of drug delivery and treatment, while preparations for biocompatible robots are extremely challenging. Here, a self-driving yeast micro-/nanorobot (Cur@CaY-robot) is designed via dual biomineralization and acid catalysis of calcium carbonate (CaCO). Inner nano-CaCO inside yeast cells (CaY) is biomineralized through cell respiration and provides nanoscaffolds for highly encapsulating curcumin (Cur).

Biomimetic Nanosonosensitizers Combined with Noninvasive Ultrasound Actuation to Reverse Drug Resistance and Sonodynamic-Enhanced Chemotherapy against Orthotopic Glioblastoma.

Glioblastoma (GBM) is the most devastating brain tumor and highly resistant to conventional chemotherapy. Herein, we introduce biomimetic nanosonosensitizer systems (MDNPs) combined with noninvasive ultrasound (US) actuation for orthotopic GBM-targeted delivery and sonodynamic-enhanced chemotherapy. MDNPs were fabricated with biodegradable and pH-sensitive polyglutamic acid (PGA) and the chemotherapeutic agent and sonosensitizer doxorubicin (DOX), camouflaged with human GBM U87 cell membranes.

Photosensitizer-loaded gold nanocages for immunogenic phototherapy of aggressive melanoma.

Malignant melanoma remains the life-threatening form of skin cancer with high mortality and poor prognosis. Thus, an ideal melanoma therapeutic strategy is of immediate importance which can remove the primary tumor, as well as inhibit the metastasis and recurrence. Here, we report the fabrication of adjuvant monophosphoryl lipid A (MPLA) lipid bilayer-enveloped and photosensitizer indocyanine green (ICG)-loaded gold nanocages (MLI-AuNCs) for immunogenic phototherapy of aggressive melanoma.

In situ poly I:C released from living cell drug nanocarriers for macrophage-mediated antitumor immunotherapy.

Immunotherapy is one of the most promising approaches to inhibit tumor growth and metastasis by activating host immune functions. However, the arising problems such as low immune response caused by complex tumor microenvironment and extremely systemic immune storm still limit the clinical applications of immunotherapy. Here, we construct Poly I: C-encapsulated poly (lactic-co-glycolic acid) nanoparticles (PLP NPs) with a slow release profile.

Noninvasively immunogenic sonodynamic therapy with manganese protoporphyrin liposomes against triple-negative breast cancer.

Sonodynamic therapy (SDT) is a promising approach for tumor treatment because of the noninvasion, and future would be perfect while it activates systemic immune responses through deep penetration to effectively avoid tumor recurrence. Here, a multifunctional nanosonosensitizer system (FA-MnPs) is designed by encapsulating manganese-protoporphyrin (MnP) into folate-liposomes. The nanoparticles of FA-MnPs not only exhibit excellent depth-responsive SDT but also simultaneously activate SDT-mediated immune response.

Click CAR-T cell engineering for robustly boosting cell immunotherapy in blood and subcutaneous xenograft tumor.

The adoptive transfer of chimeric antigen receptor-T (CAR-T) cells has shown remarkable clinical responses in hematologic malignancies. However, unsatisfactory curative results and side effects for tumor treatment are still unsolved problems. Herein we develop a click CAR-T cell engineering strategy via cell glycometabolic labeling for robustly boosting their antitumor effects and safety in vivo.

Smart gold nanocages for mild heat-triggered drug release and breaking chemoresistance.

Chemotherapy is an important modality available for cancer treatment. However, the present chemotherapy is still far from being satisfactory mainly owing to the severe side effects of the chemotherapeutic agents and drug resistance of cancer cells. Thus, reversing drug resistance by constructing an ideal chemotherapeutic strategy with the least side effects and the best efficacy is greatly needed.

In Situ Photocatalysis of TiO-Porphyrin-Encapsulated Nanosystem for Highly Efficient Oxidative Damage against Hypoxic Tumors.

Reactive oxygen species (ROS)-mediated cell apoptosis has been a significant strategy for tumor oxidative damage, while tumor hypoxia is a major bottleneck for efficiency. Here, a novel TiO-porphyrin nanosystem (FA-TiOPs) is designed by encapsulating TiO-porphyrin (TiOP) in folate-liposome. The nanosysytem can photocatalyze HO and tumor-overexpressed HO in situ generating sufficient ROS.

Tumor-targeted nanoplatform for in situ oxygenation-boosted immunogenic phototherapy of colorectal cancer.

Advanced colorectal cancer has a high mortality rate since conventional treatments have limited therapeutic effects and poor prognosis with high risks of metastasis and recurrence. Photodynamic therapy (PDT) is a promising treatment modality for the eradication of colorectal cancer, but its curative efficacy is severely affected by tumor hypoxia. Herein, we developed a core-shell gold nanocage coated with manganese dioxide and hyaluronic acid (AMH) for targeted delivery to colorectal tumors and oxygenation-boosted immunogenic phototherapy in situ.

T Cell Membrane Mimicking Nanoparticles with Bioorthogonal Targeting and Immune Recognition for Enhanced Photothermal Therapy.

Due to specific immune recognition receptors on the surface of T cells, their membranes are promising mimic nanocarriers for delivering drugs to tumor lesions. However, this single targeting strategy potentially compromises therapy efficacy for tumor targeting due to inter- and intra-heterogeneity of tumors. Azide (N) or bicyclo [6.

Surface-Functionalized Nanoparticles as Efficient Tools in Targeted Therapy of Pregnancy Complications.

Minimizing exposure of the fetus to medication and reducing adverse off-target effects in the mother are the primary challenges in developing novel drugs to treat pregnancy complications. Nanomedicine has introduced opportunities for the development of novel platforms enabling targeted delivery of drugs in pregnancy. This review sets out to discuss the advances and potential of surface-functionalized nanoparticles in the targeted therapy of pregnancy complications.

Nanophotosensitizer-engineered Salmonella bacteria with hypoxia targeting and photothermal-assisted mutual bioaccumulation for solid tumor therapy.

Bacteria-driven drug-delivery systems have attracted great attention for their enhanced therapeutic specificity and efficacy in cancer treatment. YB1, a particularly attractive genetically modified safe Salmonella Typhimurium strain, is known to penetrate hypoxic tumor cores with its self-driven properties while remarkably avoiding damage to normal tissues. Herein, nanophotosensitizers (indocyanine green (ICG)-loaded nanoparticles, INPs) were covalently attached to the surface of YB1 with amide bonds to develop a biotic/abiotic cross-linked system (YB1-INPs) for tumor precision therapy.

Metalloporphyrin Complex-Based Nanosonosensitizers for Deep-Tissue Tumor Theranostics by Noninvasive Sonodynamic Therapy.

Metal complexes are widely used as anticancer drugs, while the severe side effects of traditional chemotherapy require new therapeutic modalities. Sonodynamic therapy (SDT) provides a significantly noninvasive ultrasound (US) treatment approach by activating sonosensitizers and initiating reactive oxygen species (ROS) to damage malignant tissues. In this work, three metal 4-methylphenylporphyrin (TTP) complexes (MnTTP, ZnTTP, and TiOTTP) are synthesized and encapsulated with human serum albumin (HSA) to form novel nanosonosensitizers.

Tumor-targeted hybrid protein oxygen carrier to simultaneously enhance hypoxia-dampened chemotherapy and photodynamic therapy at a single dose.

Hypoxia is a characteristic feature of solid tumors and an important causation of resistance to chemotherapy and photodynamic therapy (PDT). It is challenging to develop efficient functional nanomaterials for tumor oxygenation and therapeutic applications. Through disulfide reconfiguration to hybridize hemoglobin and albumin, tumor-targeted hybrid protein oxygen carriers (HPOCs) were fabricated, serving as nanomedicines for precise tumor oxygenation and simultaneous enhancement of hypoxia-dampened chemotherapy and photodynamic therapy.