Biosynthesized gold nanoparticles that activate Toll-like receptors and elicit localized light-converting hyperthermia for pleiotropic tumor immunoregulation.

Manipulating the tumor immune contexture towards a more active state can result in better therapeutic outcomes. Here we describe an easily accessible bacterial biomineralization-generated immunomodulator, which we name Ausome (Au + [exo]some). Ausome comprises a gold nanoparticle core covered by bacterial components; the former affords an inducible hyperthermia effect, while the latter mobilizes diverse immune responses. Multiple pattern recognition receptors actively participate in Ausome-initiated immune responses, which lead to the release of a broad spectrum of pro-inflammatory cytokines and the activation of effector immune cells. Upon laser irradiation, tumor-accumulated Ausome elicits a hyperthermic response, which improves tissue blood perfusion and contributes to enhanced infiltration of immunostimulatory modules, including cytokines and effector lymphocytes. This immune-modulating strategy mediated by Ausome ultimately brings about a comprehensive immune reaction and selectively amplifies the effects of local antitumor immunity, enhancing the efficacy of well-established chemo- or immuno-therapies in preclinical cancer models in female mice.

The application and sustainable development of coral in traditional medicine and its chemical composition, pharmacology, toxicology, and clinical research.

This review discusses the variety, chemical composition, pharmacological effects, toxicology, and clinical research of corals used in traditional medicine in the past two decades. At present, several types of medicinal coral resources are identified, which are used in 56 formulas such as traditional Chinese medicine, Tibetan medicine, Mongolian medicine, and Uyghur medicine. A total of 34 families and 99 genera of corals are involved in medical research, with the Alcyoniidae family and Sarcophyton genus being the main research objects. Based on the structural types of compounds and the families and genera of corals, this review summarizes the compounds primarily reported during the period, including terpenoids, steroids, nitrogen-containing compounds, and other terpenoids dominated by sesquiterpene and diterpenes. The biological activities of coral include cytotoxicity (antitumor and anticancer), anti-inflammatory, analgesic, antibacterial, antiviral, immunosuppressive, antioxidant, and neurological properties, and a detailed summary of the mechanisms underlying these activities or related targets is provided. Coral toxicity mostly occurs in the marine ornamental soft coral Zoanthidae family, with palytoxin as the main toxic compound. In addition, nonpeptide neurotoxins are extracted from aquatic corals. The compatibility of coral-related preparations did not show significant acute toxicity, but if used for a long time, it will still cause toxicity to the liver, kidneys, lungs, and other internal organs in a dose-dependent manner. In clinical applications, individual application of coral is often used as a substitute for orthopedic materials to treat diseases such as bone defects and bone hyperplasia. Second, coral is primarily available in the form of compound preparations, such as Ershiwuwei Shanhu pills and Shanhu Qishiwei pills, which are widely used in the treatment of neurological diseases such as migraine, primary headache, epilepsy, cerebral infarction, hypertension, and other cardiovascular and cerebrovascular diseases. It is undeniable that the effectiveness of coral research has exacerbated the endangered status of corals. Therefore, there should be no distinction between the advantages and disadvantages of listed endangered species, and it is imperative to completely prohibit their use and provide equal protection to help them recover to their normal numbers. This article can provide some reference for research on coral chemical composition, biological activity, chemical ecology, and the discovery of marine drug lead compounds. At the same time, it calls for people to protect endangered corals from the perspectives of prohibition, substitution, and synthesis.

A Graphdiyne Oxide-Based Iron Sponge with Photothermally Enhanced Tumor-Specific Fenton Chemistry.

Fenton reaction-mediated oncotherapy is an emerging strategy which uses iron ions to catalytically convert endogenous hydrogen peroxide into hydroxyl radicals, the most reactive oxygen species found in biology, for efficient cancer therapy. However, Fenton reaction efficiency in tumor tissue is typically limited due to restrictive conditions. One strategy to overcome this obstacle is to increase the temperature specifically at the tumor site. Herein, a tumor-targeting iron sponge (TTIS) nanocomposite based on graphdiyne oxide, which has a high affinity for iron is described. TTIS can accumulate in tumor tissue by decoration with a tumor-targeting polymer to enable tumor photoacoustic and magnetic resonance imaging. With its excellent photothermal conversion efficiency (37.5%), TTIS is an efficient photothermal therapy (PTT) agent. Moreover, the heat produced in the process of PTT can accelerate the release of iron ions from TTIS and simultaneously enhance the efficiency of the Fenton reaction, thus achieving a combined PTT and Fenton reaction-mediated cancer therapy. This work introduces a graphdiyne oxide-based iron sponge that exerts an enhanced antitumor effect through PTT and Fenton chemistry.

Emerging nanomedicines for anti-stromal therapy against desmoplastic tumors.

Solid tumors, especially desmoplastic tumors, are characterized by a dense fibrotic stroma composed of abundant cancer-associated fibroblasts and excessive extracellular matrix. These physical barriers seriously compromise drug delivery to tumor cells, leading to suboptimal treatment efficacy and resistance to current tumor-centric therapeutics. The need to overcome these problems has driven extensive investigations and sparked the flourish of anti-stromal therapy, particularly in the field of nanomedicines. In this paper, we firstly review the major components of the tumor stroma and discuss their impact on drug delivery. Then, according to the different stromal targets, we summarize the current status of anti-stromal therapy and highlight recent advances in anti-stromal nanomedicines. We further examine the potential of nano-enabled anti-stromal therapy to enhance the anti-tumor efficacy of other therapeutic modalities, including chemotherapy, immunotherapy, phototherapy and radiotherapy. Finally, the potential concerns and future developments of anti-stromal nanomedicines are discussed.

An Extendable Star-Like Nanoplatform for Functional and Anatomical Imaging-Guided Photothermal Oncotherapy.

Combining informative imaging methodologies with effective treatments to destroy tumors is of great importance for oncotherapy. Versatile nanotheranostic agents that inherently possess both diagnostic imaging and therapeutic capabilities are highly desirable to meet these requirements. Here, a simple but powerful nanoplatform based on polydopamine-coated gold nanostar (GNS@PDA), which can be easily diversified to achieve various function extensions, is designed to realize functional and anatomical imaging-guided photothermal oncotherapy. This nanoplatform intrinsically enables computed tomography/photoacoustic/two-photon luminescence/infrared thermal tetramodal imaging and can further incorporate fibroblast activation protein (FAP, a protease highly expressed in most of tumors) activatable near-infrared fluorescence imaging and Fe3+-based magnetic resonance imaging for comprehensive diagnosis. Moreover, GNS@PDA exhibits excellent photothermal performance and efficient tumor accumulation. Under the precise guidance of multimodal imaging, GNS@PDA conducts homogeneous photothermal ablation of bulky solid tumors (∼200 mm3) in a xenograft mouse model. These results suggest great promise of this extendable nanoplatform for cancer theranostics.

Precision combination therapy for triple negative breast cancer via biomimetic polydopamine polymer core-shell nanostructures.

Photothermal-based combination therapy using functional nanomaterials shows great promise in eradication of aggressive tumors and improvement of drug sensitivity. The therapeutic efficacy and adverse effects of drug combinations depend on the precise control of timely tumor-localized drug release. Here a polymer-dopamine nanocomposite is designed for combination therapy, thermo-responsive drug release and prevention of uncontrolled drug leakage. The thermo-sensitive co-polymer poly (2-(2-methoxyethoxy) ethyl methacrylate-co-oligo (ethylene glycol) methacrylate)-co-2-(dimethylamino) ethyl methacrylate-b-poly (D, l-lactide-co-glycolide) is constructed into core-shell structured nanoparticles for co-encapsulation of two cytotoxic drugs and absorption of small interfering RNAs against survivin. The drug-loaded nanoparticles are surface-coated with polydopamine which confers the nanoformulation with photothermal activity and protects drugs from burst release. Under tumor-localized laser irradiation, polydopamine generates sufficient heat, resulting in nanoparticle collapse and instant drug release within the tumor. The combination strategy of photothermal, chemo-, and gene therapy leads to triple-negative breast cancer regression, with a decrease in the chemotherapeutic drug dosage to about 1/20 of conventional dose. This study establishes a powerful nanoplatform for precisely controlled combination therapy, with dramatic improvement of therapeutic efficacy and negligible side effects.

Integration of photothermal therapy and synergistic chemotherapy by a porphyrin self-assembled micelle confers chemosensitivity in triple-negative breast cancer.

Triple-negative breast cancer is a malignant cancer type with a high risk of early recurrence and distant metastasis. Unlike other breast cancers, triple-negative breast cancer is lack of targetable receptors and, therefore, patients largely receive systemic chemotherapy. However, inevitable adverse effects and acquired drug resistance severely constrain the therapeutic outcome. Here we tailor-designed a porphyrin-based micelle that was self-assembled from a hybrid amphiphilic polymer comprising polyethylene glycol, poly (d, l-lactide-co-glycolide) and porphyrin. The bilayer micelles can be simultaneously loaded with two chemotherapeutic drugs with synergistic cytotoxicity and distinct physiochemical properties, forming a uniform and spherical nanostructure. The drug-loaded micelles showed a tendency to accumulate in the tumor and can be internalized by tumor cells for drug release in acidic organelles. Under near-infrared laser irradiation, high density of self-quenched porphyrins in the hydrophobic layer absorbed light efficiently and converted into an excited state, leading to the release of sufficient heat for photothermal therapy. The integration of localized photothermal effect and synergistic chemotherapy conferred great chemosensitivity to cancer cells and achieved tumor regression using about 1/10 of traditional drug dosage. As a result, chemotherapy-associated adverse effects were successfully avoided. Our present study established a novel porphyrin-based nanoplatform with photothermal activity and expanded drug loading capacity, providing new opportunities for challenging conventional chemotherapy and fighting against stubborn triple-negative breast cancer.

Aspect ratios of gold nanoshell capsules mediated melanoma ablation by synergistic photothermal therapy and chemotherapy.

Nanomaterial-mediated photothermal therapy has shown great potential to fulfill the unmet medical needs for treatment of tumors. In this study, a rod-like gold nanoshell capsule, which can offer both photothermal therapy and chemotherapy, is synthesized and applied for the treatment of melanoma. This nano-platform is made by developing a gold nanoshell on rod-like mesoporous silica nanoparticles with different aspect ratios, and it was found that the aspect ratio significantly influenced the cellular uptake and tumor distribution of the nanoparticles. The gold nanoshell capsules with a moderate aspect ratio are found to be efficiently taken up by melanoma cells and are able to penetrate tumor tissues, resulting in the effective ablation of highly malignant melanomas when used along with mild laser irradiation and a single treatment. This study demonstrates that the optimization of the aspect ratio is indispensable to further development of this nanoplatform for antitumor therapy. FROM THE CLINICAL EDITOR: The combination of hyperthermia and chemotherapeutic agents has been investigated as a new approach for the treatment of malignant melanoma. It appears that the aspect ratio may play an important role in the treatment efficacy. In this article, the authors studied how the AR influenced the cellular uptake and the optimal AR for antitumor effects.