Functional proteins/peptides targeting to clear Amyloid-β for Alzheimer's disease therapy.

Alzheimer's disease (AD) is a significant neurodegenerative disorder primarily affecting individuals over the age of 65. It is characterized by impairments in memory, thinking, analytical judgment, visuospatial recognition, and mood. In recent years, the development of protein and peptide drugs targeting amyloid-beta (Aβ) has gained momentum, with several therapies entering clinical trials and even receiving marketing approval.

sAPPα Peptide Promotes Damaged Microglia to Clear Alzheimer's Amyloid-β via Restoring Mitochondrial Function.

Alzheimer's disease (AD) is an age-related neurodegenerative disease with amyloid-β (Aβ) deposition as the main pathological feature. It's an important challenge to find new ways to clear Aβ from the brain. The soluble amyloid precursor protein α (sAPPα) is a neuroprotective protein and can attenuate neuronal damage, including toxic Aβ.

Research progress in leveraging biomaterials for enhancing NK cell immunotherapy.

NK cell immunotherapy is a promising antitumor therapeutic modality after the development of T cell immunotherapy. Structural modification of NK cells with biomaterials may provide a precise, efficient, and low-cost strategy to enhance NK cell immunotherapy. The biomaterial modification of NK cells can be divided into two strategies: surface engineering with biomaterials and intracellular modification.

Using bio-orthogonally catalyzed lethality strategy to generate mitochondria-targeting anti-tumor metallodrugs and .

Synthetic lethality was proposed nearly a century ago by geneticists and recently applied to develop precision anti-cancer therapies. To exploit the synthetic lethality concept in the design of chemical anti-cancer agents, we developed a bio-orthogonally catalyzed lethality (BCL) strategy to generate targeting anti-tumor metallodrugs both and Metallodrug Ru-rhein was generated from two non-toxic species Ru-N and rhein-alkyne via exclusive endogenous copper-catalyzed azide alkyne cycloaddition (CuAAC) reaction without the need of an external copper catalyst. The non-toxic species Ru-arene complex Ru-N and rhein-alkyne were designed to perform this strategy, and the mitochondrial targeting product Ru-rhein was generated in high yield (>83%) and showed high anti-tumor efficacy .

Fluorine assembly nanocluster breaks the shackles of immunosuppression to turn the cold tumor hot.

Clinical investigations have shown that a nonimmunogenic "cold" tumor is usually accompanied by few immunopositive cells and more immunosuppressive cells in the tumor microenvironment (TME), which is still the bottleneck of immune activation. Here, a fluorine assembly nanocluster was explored to break the shackles of immunosuppression, reawaken the immune system, and turn the cold tumor "hot." Once under laser irradiation, FS@PMPt produces sufficient reactive oxygen species (ROS) to fracture the ROS-sensitive linker, thus releasing the cisplatin conjugated PMPt to penetrate into the tumors and kill the regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs).

Tissue-Specific Regulation of Reactive Oxygen Species by an ATP-Responsive Nanoregulator Enhances Anticancer Efficacy and Reduces Anthracycline-Induced Cardiotoxicity.

Chemotherapy plays an important role in cancer treatment, yet its clinical application is inhibited by side effects. Chemotherapeutic agents accumulate at nonspecific sites and induce oxidative stress damage in noncancer tissues. A selective approach would be ideal, which would not only enhance anticancer efficacy in the tumor sites but also reduce chemotherapy-induced adverse effects on normal tissues.

GSH depletion liposome adjuvant for augmenting the photothermal immunotherapy of breast cancer.

The high redox level of tumor microenvironment inhibits the oxidation treatment and the immune response. Here, we innovatively develop maleimide liposome (ML) adjuvants to promote immunogenic cell death (ICD) induction and dendritic cells (DCs) maturation by glutathione (GSH) depletion for augmenting the photothermal immunotherapy of breast cancer. The ML effectively depletes the intracellular GSH and up-regulates reactive oxygen species (ROS) in both tumor cells and DCs.

"Star" miR-34a and CXCR4 antagonist based nanoplex for binary cooperative migration treatment against metastatic breast cancer.

Invasion and metastasis of tumor cells is one of the major obstacles in cancer therapy. The process of tumor metastasis and diffusion is coordinated by multiple pathways associated with chemokine signals and migration microenvironment. In our previous work, chemokine CXC receptor 4 (CXCR4) antagonists showed significant anti-metastatic effects by blocking the CXCR4/stromal cell-derived factor-1(SDF-1) axis in pancreatic cancer and breast cancer.

Dual-Mode Avocado-like All-Iron Nanoplatform for Enhanced T/T MRI-Guided Cancer Theranostic Therapy.

Development of T/T dual-mode MRI contrast agents that can also treat cancer is an attractive prospect for personalized precision medicine. Unfortunately, conventional contrast agents can suffer from toxicity and lack any ability to treat cancer. An all-iron T/T MR imaging agent with photothermal and drug delivery capability would overcome these issues.

Targeting pulmonary tumor microenvironment with CXCR4-inhibiting nanocomplex to enhance anti-PD-L1 immunotherapy.

Anti-programmed cell death 1 ligand 1 (PD-L1) therapy is extraordinarily effective in select patients with cancer. However, insufficient lymphocytic infiltration, weak T cell-induced inflammation, and immunosuppressive cell accumulation in the tumor microenvironment (TME) may greatly diminish the efficacy. Here, we report development of the FX@HP nanocomplex composed of fluorinated polymerized CXCR4 antagonism (FX) and paclitaxel-loaded human serum albumin (HP) for pulmonary delivery of anti-PD-L1 small interfering RNA (siPD-L1) to treat orthotopic lung tumors.

ATP-Charged Nanoclusters Enable Intracellular Protein Delivery and Activity Modulation for Cancer Theranostics.

Protein drugs own a large share in the market and hold great prospects for the treatment of many diseases. However, the available protein drugs are limited to the extracellular target, owing to the inefficient transduction and activity modulation of proteins targeting intracellular environment. In this study, we constructed ATP-charged platforms to overcome the above-mentioned barriers for cancer theranostics.

HO-activated oxidative stress amplifier capable of GSH scavenging for enhancing tumor photodynamic therapy.

Photodynamic therapy (PDT) is a clinically approved cancer treatment approach that relies on the generation of excess reactive oxygen species (ROS) to eradicate tumor cells by inducing oxidative stress. Unfortunately, if the tumor's endogenous glutathione (GSH) is overexpressed, it will eliminate the ROS and restrict the therapeutic efficacy of PDT. Herein, we report a HO-activated oxidative stress amplifier (OSA) for enhancing the ROS generation for PDT via GSH scavenging.

A pH-sensitive coordination polymer network-based nanoplatform for magnetic resonance imaging-guided cancer chemo-photothermal synergistic therapy.

Developing various kinds of nanoplatforms with integrated diagnostic and therapeutic functions would be significant for imaging-guided precision treatment of cancer. However, it is still a challenge to organically integrate therapeutic and imaging components into a single nano-system rather than simply mixing. Herein, an iron-gallic acid network-based nanoparticle (Fe-GA@PEG-PLGA) was designed for magnetic resonance imaging (MRI)-guided chemo-photothermal synergistic therapy of tumors.

Charge-switchable polymeric complex for glucose-responsive insulin delivery in mice and pigs.

Glucose-responsive insulin delivery systems with robust responsiveness that has been validated in animal models, especially in large animal models, remain elusive. Here, we exploit a new strategy to form a micro-sized complex between a charge-switchable polymer with a glucose-sensing moiety and insulin driven by electrostatic interaction. Both high insulin loading efficiency (95%) and loading capacity (49%) can be achieved.

Photoactivated Lysosomal Escape of a Monofunctional Pt Complex Pt-BDPA for Nucleus Access.

A photosensitizing monofunctional Pt complex, Pt-BDPA, was prepared with a BODIPY chromophore. Apart from its DNA binding ability, this complex displays emission at ca. 578 nm and a singlet oxygen quantum yield of 0.

A nanoscale photothermal agent based on a metal-organic coordination polymer as a drug-loading framework for effective combination therapy.

Metallic materials are widely emerging as photothermal agents owing to their superior photothermal transduction efficiency and satisfactory photostability. In this study, an iron-based coordination polymer (Fe-CNP) loaded with doxorubicin (DOX) was assessed as a dual-function agent for photothermal therapy (PTT) and tumor-targeted chemotherapy. Fe-CNPs were synthesized by a one-step coordination reaction between Fe, hydrocaffeic acid, and dopamine-modified hyaluronic acid.

Biomimetic Hybrid Nanozymes with Self-Supplied H and Accelerated O Generation for Enhanced Starvation and Photodynamic Therapy against Hypoxic Tumors.

Nanozymes as artificial enzymes that mimicked natural enzyme-like activities have received great attention in cancer diagnosis and therapy. Biomimetic nanozymes require more consideration regarding complicated tumor microenvironments to mimic biological enzymes, thus achieving superior nanozyme activity in vivo. Here we report a biomimetic hybrid nanozyme (named rMGB) which integrates natural enzyme glucose oxidase (GOx) with nanozyme manganese dioxide (MnO) by mutual promotion for maximizing the enzymatic activity of MnO and GOx.

Light-Induced ROS Generation and 2-DG-Activated Endoplasmic Reticulum Stress by Antitumor Nanosystems: An Effective Combination Therapy by Regulating the Tumor Microenvironment.

A multimodal cancer therapeutic nanoplatform is reported. It demonstrates a promising approach to synergistically regulating the tumor microenvironment. The combination of intracellular reactive oxygen species (ROS) generated by irradiation of photosensitizer and endoplasmic reticulum (ER) stress induced by 2-deoxy-glucose (2-DG) has a profound effect on necrotic or apoptotic cell death.

ATP-activated decrosslinking and charge-reversal vectors for siRNA delivery and cancer therapy.

Stimuli-responsive polycations have been developed for improved nucleic acid transfection and enhanced therapeutic efficacy. The most reported mechanisms for controlled release of siRNA are based on polyelectrolyte exchange reactions in the cytoplasm and the degradation of polycations initiated by specific triggers. However, the degradation strategy has not always been sufficient due to unsatisfactory kinetics and binding of cationic fragments to siRNA, which limits the gene silencing effect.

Charge and Assembly Reversible Micelles Fueled by Intracellular ATP for Improved siRNA Transfection.

Hydrophobic modification on polycations were commonly used to improve the stability and transfection efficiency of polyplexes. However, the improved stability often means undesired release of the encapsulated siRNA, limiting the application of cationic micelles for siRNA delivery. The current strategy of preparing bioresponsive micelles based on the cleavage of sensitive linkages between polycation and hydrophobic part was far from sufficient, owing to the siRNA binding of the separated polycations from micelles leading to the incomplete release of siRNA.

A multifunctional ternary Cu(II)-carboxylate coordination polymeric nanocomplex for cancer thermochemotherapy.

Metal-based photothermal therapy has been widely used in the biomedicine field and includes gold nanoparticles, silver nanoparticles and copper sulfide nanoparticles. Furthermore, the coordination bonding-based metal nanocomplex is a new generation of photothermal agents for cancer therapy due to its high photothermal transduction efficiency, good biocompatibility, biodegradation and bioactivity. In this study, we designed a coordination bonding-based copper (Cu(II))-carboxylate ternary architecture, which consists of a conjugate dopamine-modified nontoxic hyaluronic acid, copper ions and citric acid.

Near-infrared light-activated IR780-loaded liposomes for anti-tumor angiogenesis and Photothermal therapy.

Tumor angiogenesis is a key step in the process of tumor development, and antitumor angiogenesis has a profound influence on tumor growth. Herein we report a dual-function drug delivery system comprising a Near-infrared (NIR) dye and an anti-angiogenic drug within liposomes (Lip-IR780-Sunitinib) for enhanced antitumor therapy. The hydrophobic NIR dye IR780 was loaded into the liposome phospholipid bilayer, and the bilayer would be disrupted by laser irradiation so that anti-angiogenic drug sunitinib release would be activated remotely at the tumor site.

Bioreduction-ruptured nanogel for switch on/off release of Bcl2 siRNA in breast tumor therapy.

In present study, gene concentrated as well as bioreduction-ruptured nanogel with local enrichment positive charge while low cytotoxicity was developed for Bcl2 siRNA delivery featured in intracellular switch on/off controlled release. Dynamic covalent bond crosslinked nanogel was formed by thiolated PEI of 1.8 kDa(PEI-1.

Conjugated polymer nanomaterials for theranostics.

Conjugated polymer nanomaterials (CPNs), as optically and electronically active materials, hold promise for biomedical imaging and drug delivery applications. This review highlights the recent advances in the utilization of CPNs in theranostics. Specifically, CPN-based in vivo imaging techniques, including near-infrared (NIR) imaging, two-photon (TP) imaging, photoacoustic (PA) imaging, and multimodal (MM) imaging, are introduced.