Chemical Antibody Mimics Inhibit Cadherin-Mediated Cell–Cell Adhesion: A Promising Strategy for Cancer Therapy

One of the most promising strategies to treat cancer is the use of therapeutic antibodies that disrupt cell–cell adhesion mediated by dysregulated cadherins. The principal site where cell–cell adhesion occurs encompasses Trp2 found at the N-terminal region of the protein. Herein, we employed the naturally exposed highly conserved peptide Asp1-Trp2-Val3-Ile4-Pro5-Pro6-Ile7, as epitope to prepare molecularly imprinted polymer nanoparticles (MIP-NPs) to recognize cadherins. Since MIP-NPs target the site responsible for adhesion, they were more potent than commercially available therapeutic antibodies for inhibiting cell–cell adhesion in cell aggregation assays, and for completely disrupting three-dimensional tumor spheroids as well as inhibiting invasion of HeLa cells. These biocompatible supramolecular anti-adhesives may potentially be used as immunotherapeutic or sensitizing agents to enhance antitumor effects of chemotherapy.     

Few‐Layer Graphene Kills Selectively Tumor Cells from Myelomonocytic Leukemia Patients

In the cure of cancer, a major cause of today's mortality, chemotherapy is the most common treatment, though serious frequent challenges are encountered by current anticancer drugs. We discovered that few‐layer graphene (FLG) dispersions have a specific killer action on monocytes, showing neither toxic nor activation effects on other immune cells. We confirmed the therapeutic application of graphene on an aggressive type of cancer that is myelomonocytic leukemia, where the monocytes are in their malignant form. We demonstrated that graphene has the unique ability to target and boost specifically the necrosis of monocytic cancer cells. Moreover, the comparison between FLG and a common chemotherapeutic drug, etoposide, confirmed the higher specificity and toxicity of FLG. Since current chemotherapy treatments of leukemia still cause serious problems, these findings open the way to new and safer therapeutic approaches.     

Reconstitution of Low‐Density Lipoproteins with Fatty Acids for the Targeted Delivery of Drugs into Cancer Cells

Low‐density lipoproteins (LDLs) are a class of nanocarriers for the targeted delivery of therapeutics into aberrant cells that overexpress the LDL receptor. A facile procedure is used for reconstituting the hydrophobic core of LDLs with a binary fatty acid mixture. Facilitated by the tumor targeting capability of the apolipoprotein, the reconstituted, drug‐loaded LDLs can effectively target cancer cells that overexpress the LDL receptor while showing minor adverse impact on normal fibroblasts. According to a hypothesized mechanism, the reconstituted LDLs can also enable metabolism‐triggered drug release while preventing the payloads from lysosomal degradation. This study demonstrates that LDLs reconstructed with fatty acids hold great promise to serve as effective and versatile nanocarriers for targeted cancer therapy.     

DNA Trojan Horses: Self‐Assembled Floxuridine‐Containing DNA Polyhedra for Cancer Therapy

Based on their structural similarity to natural nucleobases, nucleoside analogue therapeutics were integrated into DNA strands through conventional solid‐phase synthesis. By elaborately designing their sequences, floxuridine‐integrated DNA strands were synthesized and self‐assembled into well‐defined DNA polyhedra with definite drug‐loading ratios as well as tunable size and morphology. As a novel drug delivery system, these drug‐containing DNA polyhedra could ideally mimic the Trojan Horse to deliver chemotherapeutics into tumor cells and fight against cancer. Both in vitro and in vivo results demonstrate that the DNA Trojan horse with buckyball architecture exhibits superior anticancer capability over the free drug and other formulations. With precise control over the drug‐loading ratio and structure of the nanocarriers, the DNA Trojan horse may play an important role in anticancer treatment and exhibit great potential in translational nanomedicine.     

Organic Semiconducting Pro‐nanostimulants for Near‐Infrared Photoactivatable Cancer Immunotherapy

In this study, an organic semiconducting pro‐nanostimulant (OSPS) with a near‐infrared (NIR) photoactivatable immunotherapeutic action for synergetic cancer therapy is presented. OSPS comprises a semiconducting polymer nanoparticle (SPN) core and an immunostimulant conjugated through a singlet oxygen (¹O₂) cleavable linkers. Upon NIR laser irradiation, OSPS generates both heat and ¹O₂ to exert combinational phototherapy not only to ablate tumors but also to produce tumor‐associated antigens. More importantly, NIR irradiation triggers the cleavage of ¹O₂‐cleavable linkers, triggering the remote release of the immunostimulants from OSPS to modulate the immunosuppressive tumor microenvironment. Thus, the released tumor‐associated antigens in conjunction with activated immunostimulants induce a synergistic antitumor immune response after OSPS‐mediated phototherapy, resulting in the inhibited growth of both primary/distant tumors and lung metastasis in a mouse xenograft model, which is not observed for sole phototherapy.     

Activatable Singlet Oxygen Generation from Lipid Hydroperoxide Nanoparticles for Cancer Therapy

Reactive oxygen species (ROS)-induced apoptosis is a widely practiced strategy for cancer therapy. Although photodynamic therapy (PDT) takes advantage of the spatial–temporal control of ROS generation, the meticulous participation of light, photosensitizer, and oxygen greatly hinders the broad application of PDT as a first-line cancer treatment option. An activatable system has been developed that enables tumor-specific singlet oxygen (¹O₂) generation for cancer therapy, based on a Fenton-like reaction between linoleic acid hydroperoxide (LAHP) tethered on iron oxide nanoparticles (IO NPs) and the released iron(II) ions from IO NPs under acidic-pH condition. The IO-LAHP NPs are able to induce efficient apoptotic cancer cell death both in vitro and in vivo through tumor-specific ¹O₂ generation and subsequent ROS mediated mechanism. This study demonstrates the effectiveness of modulating biochemical reactions as a ROS source to exert cancer death.     

A Water‐Soluble,NIR‐Absorbing Quaterrylenediimide Chromophore for Photoacoustic Imaging and Efficient Photothermal Cancer Therapy

Precision phototheranostics, including photoacoustic imaging and photothermal therapy, requires stable photothermal agents. Developing such agents with high stability and high photothermal conversion efficiency (PTCE) remains a considerable challenge. Herein, we introduce a new photothermal agent based on water‐soluble quaterrylenediimide (QDI) that can self‐assemble into nanoparticles (QDI‐NPs) in aqueous solution. Incorporating polyethylene glycol (PEG) into the QDI core significantly enhances both physiological stability and biocompatibility of QDI‐NPs. The highly photostable QDI‐NPs offer advantages including intense absorption in the near‐infrared (NIR) and high PTCE of up to 64.7±4 %. This is higher than that of commercial indocyanine green (ICG). Their small size (ca. 10 nm) enables sustained retention in deep tumor sites and also proper clearance from the body. QDI‐NPs allow high‐resolution photoacoustic imaging and efficient 808 nm laser‐triggered photothermal therapy of cancer in vivo.