Ferrous-Supply-Regeneration Nanoengineering for Cancer-Cell-Specific Ferroptosis in Combination with Imaging-Guided Photodynamic Therapy.

Non-apoptotic ferroptosis is of clinical importance because it offers a solution to the inevitable biocarriers of traditional apoptotic therapeutic means. Inspired by industrial electro-Fenton technology featured with electrochemical iron cycling, we construct ferrous-supply-regeneration nanoengineering to intervene tumorous iron metabolism for enhanced ferroptosis. Fe ion and naturally derived tannic acid (TA) spontaneously form a network-like corona onto sorafenib (SRF) nanocores.

Paeoniflorin-6'-O-benzene sulfonate alleviates collagen-induced arthritis in mice by downregulating BAFF-TRAF2-NF-κB signaling: comparison with biological agents.

Paeoniflorin-6'-O-benzene sulfonate (CP-25) is a new ester derivative of paeoniflorin with improved lipid solubility and oral bioavailability, as well as better anti-inflammatory activity than its parent compound. In this study we explored whether CP-25 exerted therapeutic effects in collagen-induced arthritis (CIA) mice through regulating B-cell activating factor (BAFF)-BAFF receptors-mediated signaling pathways. CIA mice were given CP-25 or injected with biological agents rituximab or etanercept for 40 days.

An Adenosine Triphosphate-Responsive Autocatalytic Fenton Nanoparticle for Tumor Ablation with Self-Supplied HO and Acceleration of Fe(III)/Fe(II) Conversion.

Chemodynamic therapy (CDT) can efficiently destroy tumor cells via Fenton reaction in the presence of HO and a robust catalyst. However, it has faced severe challenges including the limited amounts of HO and inefficiency of catalysts. Here, an adenosine triphosphate (ATP)-responsive autocatalytic Fenton nanosystem (GOx@ZIF@MPN), incorporated with glucose oxidase (GOx) in zeolitic imidazolate framework (ZIF) and then coated with metal polyphenol network (MPN), was designed and synthesized for tumor ablation with self-supplied HO and TA-mediated acceleration of Fe(III)/Fe(II) conversion.

Photo-Powered Artificial Organelles for ATP Generation and Life-Sustainment.

Adenosine triphosphate (ATP) is the most important immediate energy source for driving intracellular biochemical reactions in nearly all life forms. Controllable generation of ATP in life is still an unrealized goal. Here, thylakoid fragments are recombined with lipid molecules to synthesize a synthetic/biological hybrid proteoliposome, named highly efficient life-support intracellular opto-driven system (HELIOS) for the generation of ATP.

Tumor Starvation Induced Spatiotemporal Control over Chemotherapy for Synergistic Therapy.

By integrating the characteristics of each therapy modality and material chemistry, a multitherapy modality is put forward: tumor starvation triggered synergism with sensitized chemotherapy. Following starvation-induced amplification of pathological abnormalities in tumors, chemotherapy is arranged to be locally activated and accurately reinforced to perfect multitherapy synergism from spatial and temporal perspectives. To this end, glucose oxidase (GOD) and a hypoxic prodrug of tirapazamine (TPZ) are loaded in acidity-decomposable calcium carbonate (CaCO ) nanoparticles concurrently tethered by hyaluronic acid.

Real-Time Imaging of Free Radicals for Mitochondria-Targeting Hypoxic Tumor Therapy.

Free radicals have emerged as new-type and promising candidates for hypoxic tumor treatment, and further study of their therapeutic mechanism by real-time imaging is of great importance to explore their biomedical applications. Herein, we present a smart free-radical generator AuNC-V057-TPP for hypoxic tumor therapy; the AuNC-V057-TPP not only exhibits good therapeutic effect under both hypoxic and normoxic conditions but also can monitor the release of free radicals in real-time both in vitro and in vivo. What is more, with the mitochondria-targeting ability, the AuNC-V057-TPP is demonstrated with improved antitumor efficacy through enhanced free radical level in mitochondria, which leads to mitochondrial membrane damage and ATP production reduction and finally induces cancer cell apoptosis.

Mitochondria and plasma membrane dual-targeted chimeric peptide for single-agent synergistic photodynamic therapy.

Mitochondria and cell membrane play important roles in maintaining cellular activity and stability. Here, a single-agent self-delivery chimeric peptide based nanoparticle (designated as M-ChiP) was developed for mitochondria and plasma membrane dual-targeted photodynamic tumor therapy. Without additional carrier, M-ChiP possessed high drug loading efficacy as well as the excellent ability of producing reactive oxygen species (ROS).

Recent Advances in Subcellular Targeted Cancer Therapy Based on Functional Materials.

Recently, diverse functional materials that take subcellular structures as therapeutic targets are playing increasingly important roles in cancer therapy. Here, particular emphasis is placed on four kinds of therapies, including chemotherapy, gene therapy, photodynamic therapy (PDT), and hyperthermal therapy, which are the most widely used approaches for killing cancer cells by the specific destruction of subcellular organelles. Moreover, some non-drug-loaded nanoformulations (i.

Recent Advances in Targeted Tumor Chemotherapy Based on Smart Nanomedicines.

Efficacy and safety of chemotherapeutic drugs constitute two major criteria in tumor chemotherapy. Nanomedicines with tumor-targeted properties hold great promise for improving the efficacy and safety. To design targeted nanomedicines, the pathological characteristics of tumors are extensively and deeply excavated.

ROS-induced NO generation for gas therapy and sensitizing photodynamic therapy of tumor.

This study reports a tumor-specific ROS-responsive nanoplatform capable of the combination of nitric oxide (NO)-based gas therapy and sensitized photodynamic therapy (PDT). The nanoplatform is constructed on porous coordination network (PCN), which contains NO donor L-Arg and is concurrently coated with cancer cell membrane (L-Arg@PCN@Mem). Under near infrared light (NIR) irradiation, L-Arg@PCN@Mem produces plenty of reactive oxygen species (ROS) directly for PDT therapy, while a part of ROS take the role of oxidative to converse L-Arg into NO for combined gas therapy.

Metalloporphyrin-bound Janus nanocomposites with dual stimuli responsiveness for nanocatalysis in living radical polymerization.

The capability to spatiotemporally regulate polymerization kinetics in response to dual external stimuli of light and magnetism offers exciting pathways to precisely manipulate polymer composition and sequence. Herein, we report a strategy that adopts snowman-shaped FeO@aSiO-click-ZnPTPP Janus nanocomposites with a high magnetization value (12.9 emu g) and stably confined but accessible catalytic metalloporphyrin moieties as the nanocatalysts for photo-induced electron transfer reversible addition-fragmentation chain transfer (PET-RAFT) polymerization.

PD-1 Blockade for Improving the Antitumor Efficiency of Polymer-Doxorubicin Nanoprodrug.

Chemotherapy is well recognized to induce immune responses during some chemotherapeutic drugs-mediated tumor eradication. Here, a strategy involving blocking programmed cell death protein 1 (PD-1) to enhance the chemotherapeutic effect of a doxorubicin nanoprodrug HA-Psi-DOX is proposed and the synergetic mechanism between them is further studied. The nanoprodrugs are fabricated by conjugating doxorubicin (DOX) to an anionic polymer hyaluronic acid (HA) via a tumor overexpressed matrix metalloproteinase sensitive peptide (CPLGLAGG) for tumor targeting and enzyme-activated drug release.

A dual-responsive, hyaluronic acid targeted drug delivery system based on hollow mesoporous silica nanoparticles for cancer therapy.

In this study, a novel drug delivery system (HMSNs-SS-HA) based on hollow mesoporous silica nanoparticles (HMSNs) was developed for delivering anticancer drugs (e.g., doxorubicin (DOX)) to targeted tumour cells by using disulfide bonds as redox-sensitive linkers and hyaluronic acid (HA) molecules as both capping and targeting agents.

Aggressive Man-Made Red Blood Cells for Hypoxia-Resistant Photodynamic Therapy.

Extreme hypoxia of tumors represents the most notable barrier against the advance of tumor treatments. Inspired by the biological nature of red blood cells (RBCs) as the primary oxygen supplier in mammals, an aggressive man-made RBC (AmmRBC) is created to combat the hypoxia-mediated resistance of tumors to photodynamic therapy (PDT). Specifically, the complex formed between hemoglobin and enzyme-mimicking polydopamine, and polydopamine-carried photosensitizer is encapsulated inside the biovesicle that is engineered from the recombined RBC membranes.

A Simply Modified Lymphocyte for Systematic Cancer Therapy.

Cytotherapy has received considerable attention in the field of cancer therapy, and various chemical or genetic methods have been applied to remold natural cells for improved therapeutic outcome of cytotherapy. A simple method to modify lymphocytes for cancer treatment by using a clinically used molecule, δ-aminolevulinic acid (δ-ALA), is reported here. After incubation with this molecule, tumor-targeted lymphocytes spontaneously synthesize anti-neoplastic drug protoporphyrin X (PpIX), and specifically accumulate in cancer tissue.

A Multifunctional Biomimetic Nanoplatform for Relieving Hypoxia to Enhance Chemotherapy and Inhibit the PD-1/PD-L1 Axis.

Hypoxia is reported to participate in tumor progression, promote drug resistance, and immune escape within tumor microenvironment, and thus impair therapeutic effects including the chemotherapy and advanced immunotherapy. Here, a multifunctional biomimetic core-shell nanoplatform is reported for improving synergetic chemotherapy and immunotherapy. Based on the properties including good biodegradability and functionalities, the pH-sensitive zeolitic imidazolate framework 8 embedded with catalase and doxorubicin constructs the core and serves as an oxygen generator and drug reservoir.

Normalizing Tumor Microenvironment Based on Photosynthetic Abiotic/Biotic Nanoparticles.

Tumor hypoxia has attained the status of a core hallmark of cancer that globally affects the entire tumor phenotype. Reversing tumor hypoxia might offer alternative therapeutic opportunities for current anticancer therapies. In this research, a photosynthetic leaf-inspired abiotic/biotic nano-thylakoid (PLANT) system was designed by fusing the thylakoid membrane with synthetic nanoparticles for efficient O generation in vivo.

Hierarchical Micro-/Nanostructures from Human Hair for Biomedical Applications.

With the prominent progress of biomedical engineering, materials with high biocompatibility and versatile functions are urgently needed. So far, hierarchical structures in nature have shed some light on the design of high performance materials both in concept and implementation. Inspired by these, the hierarchical micro-/nanostructures of human hair are explored and human hair is further broken into hierarchical microparticles (HMP) and hierarchical nanoparticles (HNP) with top-down procedures.

Controlled Nucleation and Controlled Growth for Size Predicable Synthesis of Nanoscale Metal-Organic Frameworks (MOFs): A General and Scalable Approach.

Nanoscale metal-organic frameworks (nanoMOFs) are promising porous nanomaterials for diverse applications, such as catalysis, imaging, functional membranes, and drug delivery. At the nanoscale, the size of materials is critical for their properties and utility. Herein, a straightforward and convenient strategy is developed for size precisely controlled synthesis of nanoMOFs.

Optically-controlled bacterial metabolite for cancer therapy.

Bacteria preferentially accumulating in tumor microenvironments can be utilized as natural vehicles for tumor targeting. However, neither current chemical nor genetic approaches alone can fully satisfy the requirements on both stability and high efficiency. Here, we propose a strategy of "charging" bacteria with a nano-photocatalyst to strengthen their metabolic activities.

Combinational strategy for high-performance cancer chemotherapy.

The clinical outcomes of conventional mono-chemotherapy of cancers are usually far from satisfactory due to some issues such as tumor heterogeneity and resistance to chemotherapeutic drugs. With the increasing knowledge of molecular signal pathways and pathological mechanisms involved in the initiation and progression of cancers, collaborative strategies have been elaborated to optimize therapeutic outcomes. This review surveys the most recent advances in combination therapy including combination chemotherapy, chemotherapy plus gene therapy, chemotherapy plus phototherapy, as well as chemotherapy plus immunotherapy.

Virus-Inspired Nanogenes Free from Man-Made Materials for Host-Specific Transfection and Bio-Aided MR Imaging.

Many viruses have a lipid envelope derived from the host cell membrane that contributes much to the host specificity and the cellular invasion. This study puts forward a virus-inspired technology that allows targeted genetic delivery free from man-made materials. Genetic therapeutics, metal ions, and biologically derived cell membranes are nanointegrated.

Double-Targeting Explosible Nanofirework for Tumor Ignition to Guide Tumor-Depth Photothermal Therapy.

This study reports a double-targeting "nanofirework" for tumor-ignited imaging to guide effective tumor-depth photothermal therapy (PTT). Typically, ≈30 nm upconversion nanoparticles (UCNP) are enveloped with a hybrid corona composed of ≈4 nm CuS tethered hyaluronic acid (CuS-HA). The HA corona provides active tumor-targeted functionality together with excellent stability and improved biocompatibility.

MnO Motor: A Prospective Cancer-Starving Therapy Promoter.

Here, a tumor-targeted MnO motor nanosystem (designed as MG/HA) was constructed by the assembly of glucose oxidase (GOD), manganese dioxide (MnO), and glycoprotein CD44-targeting polymer hyaluronic acid (HA) to elevate cancer-starving therapy efficacy in solid tumor. Upon the specific uptake of MG/HA by CD44 overexpressed cancer cells, GOD catalyzed the oxidation of glucose into gluconic acid and hydrogen peroxide (HO) accompanying the consumption of oxygen (O). Meanwhile, MnO would react with HO and acid to generate O, which is in turn supplied to the glucose-depletion process, running like a loop.

A Universal Approach to Render Nanomedicine with Biological Identity Derived from Cell Membranes.

Biomimetic nanoengineering built through integrating the specific cell membrane with artificially synthetic nanomedicines represents one of the most promising directions for the actualization of personalized therapy. For addressing the technical hurdle against the development of this biomimetic technology, the present report describes the in-depth exploration and optimization over each critical preparation step, including establishment of a nanoparticle-stabilized dispersion system, cargo loading, membrane coating, and product isolation. Magnetic iron oxide nanoparticles loaded with DOX is used as a typical model for the coating with cancer cell membranes, providing compact DNP@CCCM nanostructure well-characterized by various techniques.