Bone-Targeted Supramolecular Nanoagonist Assembled by Accurate Ratiometric Herbal-Derived Therapeutics for Osteoporosis Reversal.

Developing novel strategies for defeating osteoporosis has become a world-wide challenge with the aging of the population. In this work, novel supramolecular nanoagonists (NAs), constructed from alkaloids and phenolic acids, emerge as a carrier-free nanotherapy for efficacious osteoporosis treatment. These precision nanoagonists are formed through the self-assembly of berberine (BER) and chlorogenic acid (CGA), utilizing noncovalent electrostatic, π-π, and hydrophobic interactions. This assembly results in a 100% drug loading capacity and stable nanostructure. Furthermore, the resulting weights and proportions of CGA and BER within the NAs are meticulously controlled with strong consistency when the CGA/BER assembly feed ratio is altered from 1:1 to 1:4. As anticipated, our NAs themselves could passively target osteoporotic bone tissues following prolonged blood circulation, modulate Wnt signaling, regulate osteogenic differentiation, and ameliorate bone loss in ovariectomy-induced osteoporotic mice. We hope this work will open a new strategy to design efficient herbal-derived Wnt NAs for dealing with intractable osteoporosis.

Nanoassemblies of heptamethine cyanine dye-initiated poly(amino acid) enhance ROS generation for effective antitumour phototherapy.

Phototherapy shows great potential for pinpoint tumour treatment. Heptamethine cyanine dyes like IR783 have high potential as agents for antitumour phototherapy due to their inherent tumour targeting ability, though their effectiveness in vivo is unsatisfactory for clinical translation. To overcome this limitation, we present an innovative strategy involving IR783-based polymeric nanoassemblies that improve the dye's performance as an antitumoural photosensitizer. In the formulation, IR783 is modified with cysteamine and used to initiate the ring-opening polymerization (ROP) of the N-carboxyanhydride of benzyl-L-aspartate (BLA), resulting in IR783-installed poly(BLA). Compared to free IR783, the IR783 dye in the polymer adopts a twisted molecular conformation and tuned electron orbital distribution, remarkably enhancing its optical properties. In aqueous environments, the polymers spontaneously assemble into nanostructures with 60 nm diameter, showcasing surface-exposed IR783 dyes that function as ligands for cancer cell and mitochondria targeting. Moreover, the nanoassemblies stabilized the dyes and enhanced the generation of reactive oxygen species (ROS) upon laser irradiation. Thus, in murine tumor models, a single injection of the nanoassemblies with laser irradiation significantly inhibits tumour growth with no detectable off-target toxicity. These findings highlight the potential for improving the performance of heptamethine cyanine dyes in antitumor phototherapy through nano-enabled strategies.

Nanomaterials-assisted photothermal therapy for breast cancer: State-of-the-art advances and future perspectives.

Breast cancer (BC) remains an enigmatic fatal modality ubiquitously prevalent in different parts of the world. Contemporary medicines face severe challenges in remediating and healing breast cancer. Due to its spatial specificity and nominal invasive therapeutic regime, photothermal therapy (PTT) has attracted much scientific attention down the lane. PTT utilizes a near-infrared (NIR) light source to irradiate the tumor target intravenously or non-invasively, which is converted into heat energy over an optical fibre. Dynamic progress in nanomaterial synthesis was achieved with specialized visual, physicochemical, biological, and pharmacological features to make up for the inadequacies and expand the horizon of PTT. Numerous nanomaterials have substantial NIR absorption and can function as efficient photothermal transducers. It is achievable to limit the wavelength range of an absorbance peak for specific nanomaterials by manipulating their synthesis, enhancing the precision and quality of PTT. Along the same lines, various nanomaterials are conjugated with a wide range of surface-modifying chemicals, including polymers and antibodies, which may modify the persistence of the nanomaterial and diminish toxicity concerns. In this article, we tend to put forth specific insights and fundamental conceptualizations on pre-existing PTT and its advances upon conjugation with different biocompatible nanomaterials working in synergy to combat breast cancer, encompassing several strategies like immunotherapy, chemotherapy, photodynamic therapy, and radiotherapy coupled with PTT. Additionally, the role or mechanisms of nanoparticles, as well as possible alternatives to PTT, are summarized as a distinctive integral aspect in this article.

2D Nanomaterials and Their Drug Conjugates for Phototherapy and Magnetic Hyperthermia Therapy of Cancer and Infections.

Photothermal therapy (PTT) and magnetic hyperthermia therapy (MHT) using 2D nanomaterials (2DnMat) have recently emerged as promising alternative treatments for cancer and bacterial infections, both important global health challenges. The present review intends to provide not only a comprehensive overview, but also an integrative approach of the state-of-the-art knowledge on 2DnMat for PTT and MHT of cancer and infections. High surface area, high extinction coefficient in near-infra-red (NIR) region, responsiveness to external stimuli like magnetic fields, and the endless possibilities of surface functionalization, make 2DnMat ideal platforms for PTT and MHT. Most of these materials are biocompatible with mammalian cells, presenting some cytotoxicity against bacteria. However, each material must be comprehensively characterized physiochemically and biologically, since small variations can have significant biological impact. Highly efficient and selective in vitro and in vivo PTTs for the treatment of cancer and infections are reported, using a wide range of 2DnMat concentrations and incubation times. MHT is described to be more effective against bacterial infections than against cancer therapy. Despite the promising results attained, some challenges remain, such as improving 2DnMat conjugation with drugs, understanding their in vivo biodegradation, and refining the evaluation criteria to measure PTT or MHT effects.

Enhancing Cancer Chemo-Immunotherapy: Innovative Approaches for Overcoming Immunosuppression by Functional Nanomaterials.

Chemotherapy is a critical modality in cancer therapy to combat malignant cell proliferation by directly attacking cancer cells and inducing immunogenic cell death, serving as a vital component of multi-modal treatment strategies for enhanced therapeutic outcomes. However, chemotherapy may inadvertently contribute to the immunosuppression of the tumor microenvironment (TME), inducing the suppression of antitumor immune responses, which can ultimately affect therapeutic efficacy. Chemo-immunotherapy, combining chemotherapy and immunotherapy in cancer treatment, has emerged as a ground-breaking approach to target and eliminate malignant tumors and revolutionize the treatment landscape, offering promising, durable responses for various malignancies. Notably, functional nanomaterials have substantially contributed to chemo-immunotherapy by co-delivering chemo-immunotherapeutic agents and modulating TME. In this review, recent advancements in chemo-immunotherapy are thus summarized to enhance treatment effectiveness, achieved by reversing the immunosuppressive TME (ITME) through the exploitation of immunotherapeutic drugs, or immunoregulatory nanomaterials. The effects of two-way immunomodulation and the causes of immunoaugmentation and suppression during chemotherapy are illustrated. The current strategies of chemo-immunotherapy to surmount the ITME and the functional materials to target and regulate the ITME are discussed and compared. The perspective on tumor immunosuppression reversal strategy is finally proposed.

The Emerging Landscape for Combating Resistance Associated with Energy-Based Therapies via Nanomedicine.

Cancer represents a serious disease with significant implications for public health, imposing substantial economic burden and negative societal consequences. Compared to conventional cancer treatments, such as surgery and chemotherapy, energy-based therapies (ET) based on athermal and thermal ablation provide distinct advantages, including minimally invasive procedures and rapid postoperative recovery. Nevertheless, due to the complex pathophysiology of many solid tumors, the therapeutic effectiveness of ET is often limited. Nanotechnology offers unique opportunities by enabling facile material designs, tunable physicochemical properties, and excellent biocompatibility, thereby further augmenting the outcomes of ET. Numerous nanomaterials have demonstrated the ability to overcome intrinsic therapeutic resistance associated with ET, leading to improved antitumor responses. This comprehensive review systematically summarizes the underlying mechanisms of ET-associated resistance (ETR) and highlights representative applications of nanoplatforms used to mitigate ETR. Overall, this review emphasizes the recent advances in the field and presents a detailed account of novel nanomaterial designs in combating ETR, along with efforts aimed at facilitating their clinical translation.

Post-Graphene 2D Materials: Structures, Properties, and Cancer Therapy Applications.

Cancer is one of the most serious diseases challenging human health and life span. Cancer has claimed millions of lives worldwide. Early diagnosis and effective treatment of cancer are very important for the survival of patients. In recent years, 2D nanomaterials have shown great potential in the development of anticancer treatment by combining their inherent physicochemical properties after surface modification. 2D nanomaterials have attracted great interest due to their unique nanosheet structure, large surface area, and extraordinary physicochemical properties. This article reviews the advantages and application status of emerging 2D nanomaterials for targeted tumor synergistic therapy compared with traditional therapeutic strategies. In order to investigate novel potential anticancer strategies, this paper focuses on the surface modification, cargo delivery capability, and unique optical properties of emerging 2D nanomaterials. Finally, the current problems and challenges in cancer treatment are summarized and prospected.

Multifunctional Nanoplatform for NIR-II Imaging-Guided Synergistic Oncotherapy.

Tumors are a major public health issue of concern to humans, seriously threatening the safety of people's lives and property. With the increasing demand for early and accurate diagnosis and efficient treatment of tumors, noninvasive optical imaging (including fluorescence imaging and photoacoustic imaging) and tumor synergistic therapies (phototherapy synergistic with chemotherapy, phototherapy synergistic with immunotherapy, etc.) have received increasing attention. In particular, light in the near-infrared second region (NIR-II) has triggered great research interest due to its penetration depth, minimal tissue autofluorescence, and reduced tissue absorption and scattering. Nanomaterials with many advantages, such as high brightness, great photostability, tunable photophysical properties, and excellent biosafety offer unlimited possibilities and are being investigated for NIR-II tumor imaging-guided synergistic oncotherapy. In recent years, many researchers have tried various approaches to investigate nanomaterials, including gold nanomaterials, two-dimensional materials, metal sulfide oxides, polymers, carbon nanomaterials, NIR-II dyes, and other nanomaterials for tumor diagnostic and therapeutic integrated nanoplatform construction. In this paper, the application of multifunctional nanomaterials in tumor NIR-II imaging and collaborative therapy in the past three years is briefly reviewed, and the current research status is summarized and prospected, with a view to contributing to future tumor therapy.

Nanozyme: a rising star for cancer therapy.

In recent years, nanozymes have attracted enormous attention due to their effectiveness in promoting various catalytic reactions. To date, thousands of nanozymes have been discovered, including oxidase-like nanozymes, peroxidase-like nanozymes, and catalase-like nanozymes, covering noble metal, transition metal, and carbon nanomaterials. These nanozymes have been widely applied in various fields, including environmental protection, biosensing and nanomedicine. There are many reviews about this rising star being used in analytical chemistry. However, few works about nanozymes were related to cancer therapy. In this study, we comprehensively summarize the latest research advances on the strategies for cancer therapy based on different nanozymes. With traditional cancer treatment (including chemotherapy, radiotherapy, phototherapy), nanozyme catalytic therapy exhibited a synergistic effect for limiting the growth of tumors. Opportunities and trends for nanozymes in future cancer therapy are also discussed.

Carbonaceous Nanomaterials for Phototherapy of Cancer.

Carbonaceous nanomaterials (CNMs) have drawn tremendous biomedical research interest because of their unique structural features. Recently, CNMs, namely carbon dots, fullerenes, graphene, etc, have been successful in establishing them as considerable nanotherapeutics for phototherapy applications due to their electrical, thermal, and surface properties. This review aims to crosstalk the current understanding of CNMs as multimodal compounds in photothermal and photodynamic therapies as an integrated approach to treating cancer. It also expounds on phototherapy's biomechanics and illustrates its relation to cancer biomodulation. Critical considerations related to the structural properties, fabrication approaches, surface functionalization strategies, and biosafety profiles of CNMs have been explained. This article provides an overview of the most recent developments in the study of CNMs used in phototherapy, emphasizing their usage as nanocarriers. To conquer the current challenges of CNMs, we can raise the standard of cancer therapy for patients. The review will be of interest to the researchers working in the area of photothermal and photodynamic therapies and aiming to explore CNMs and their conjugates in cancer therapy.

Trends in Photothermal Nanostructures for Antimicrobial Applications.

The rapid development of antimicrobial resistance due to broad antibiotic utilisation in the healthcare and food industries and the non-availability of novel antibiotics represents one of the most critical public health issues worldwide. Current advances in nanotechnology allow new materials to address drug-resistant bacterial infections in specific, focused, and biologically safe ways. The unique physicochemical properties, biocompatibility, and wide range of adaptability of nanomaterials that exhibit photothermal capability can be employed to develop the next generation of photothermally induced controllable hyperthermia as antibacterial nanoplatforms. Here, we review the current state of the art in different functional classes of photothermal antibacterial nanomaterials and strategies to optimise antimicrobial efficiency. The recent achievements and trends in developing photothermally active nanostructures, including plasmonic metals, semiconductors, and carbon-based and organic photothermal polymers, and antibacterial mechanisms of action, including anti-multidrug-resistant bacteria and biofilm removal, will be discussed. Insights into the mechanisms of the photothermal effect and various factors influencing photothermal antimicrobial performance, emphasising the structure-performance relationship, are discussed. We will examine the photothermal agents' functionalisation for specific bacteria, the effects of the near-infrared light irradiation spectrum, and active photothermal materials for multimodal synergistic-based therapies to minimise side effects and maintain low costs. The most relevant applications are presented, such as antibiofilm formation, biofilm penetration or ablation, and nanomaterial-based infected wound therapy. Practical antibacterial applications employing photothermal antimicrobial agents, alone or in synergistic combination with other nanomaterials, are considered. Existing challenges and limitations in photothermal antimicrobial therapy and future perspectives are presented from the structural, functional, safety, and clinical potential points of view.

Nanostructures in Chinese herbal medicines (CHMs) for potential therapy.

With its long clinical history, traditional Chinese medicine (TCM) has gained acceptance for its specific efficacy and safety in the treatment of multiple diseases. Nano-sized materials study of Chinese herbal medicines (CHMs) leads to an increased understanding of assessing TCM therapies, which may be a promising way to illustrate the material basis of CHMs through their processing and extraction. In this review, we provide an overview of the nanostructures of natural and engineered CHMs, including extracted CHMs, polymer nanoparticles, liposomes, micelles, and nanofibers. Subsequently, the applications of these CHM-derived nanostructures to particular diseases are summarized and discussed. Additionally, we discuss the advantages of these nanostructures for studying the therapeutic efficacy of CHMs. Finally, the key challenges and opportunities for the development of these nanostructures are outlined.

Nanostructured bioactive glasses: A bird's eye view on cancer therapy.

Bioactive glasses (BGs) arewell known for their successful applications in tissue engineering and regenerative medicine. Recent experimental studies have shown their potential usability in oncology, either alone or in combination with other biocompatible materials, such as biopolymers. Direct contact with BG particles has been found to cause toxicity and death in specific cancer cells (bone-derived neoplastic stromal cells) in vitro. Nanostructured BGs (NBGs) can be doped with anticancer elements, such as gallium, to enhance their toxic effects against tumor cells. However, the molecular mechanisms and intracellular targets for anticancer compositions of NBGs require further clarification. NBGs have been successfully evaluated for use in various well-established cancer treatment strategies, including cancer hyperthermia, phototherapy, and anticancer drug delivery. Existing results indicate that NBGs not only enhance cancer cell death, but can also participate in the regeneration of lost healthy tissues. However, the application of NBGs in oncology is still in its early stages, and numerous unanswered questions must be addressed. For example, the impact of the composition, biodegradation, size, and morphology of NBGs on their anticancer efficacy should be defined for each type of cancer and treatment strategy. Moreover, it should be more clearly assessed whether NBGs can shrink tumors, slow/stop cancer progression, or cure cancer completely. In this regard, the use of computational studies (in silico methods) is highly recommended to design the most effective glass formulations for cancer therapy approaches and to predict, to some extent, the relevant properties, efficacy, and outcomes. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Nanostructure-Driven Indocyanine Green Dimerization Generates Ultra-Stable Phototheranostics Nanoparticles.

Indocyanine green (ICG) is the only near-infrared (NIR) dye approved for clinical use. Despite its versatility in photonic applications and potential for photothermal therapy, its photobleaching hinders its application. Here we discovered a nanostructure of dimeric ICG (Nano-dICG) generated by using ICG to stabilize nanoemulsions, after which ICG enabled complete dimerization on the nanoemulsion shell, followed by J-aggregation of ICG-dimer, resulting in a narrow, red-shifted (780 nm→894 nm) and intense (≈2-fold) absorbance. Compared to ICG, Nano-dICG demonstrated superior photothermal conversion (2-fold higher), significantly reduced photodegradation (-9.6 % vs. -46.3 %), and undiminished photothermal effect (7 vs. 2 cycles) under repeated irradiations, in addition to excellent colloidal and structural stabilities. Following intravenous injection, Nano-dICG enabled real-time tracking of its delivery to mouse tumors within 24 h by photoacoustic imaging at NIR wavelength (890 nm) distinct from the endogenous signal to guide effective photothermal therapy. The unprecedented finding of nanostructure-driven ICG dimerization leads to an ultra-stable phototheranostic platform.

Second Near-Infrared Plasmonic Nanomaterials for Photoacoustic Imaging and Photothermal Therapy.

Photoacoustic imaging (PAI) and imaging-guided photothermal therapy (PTT) in the second near-infrared window (NIR-II, 1000-1700 nm) have received increasing attention owing to their advantages of greater penetration depth and higher signal-to-noise ratio. Plasmonic nanomaterials with tunable optical properties and strong light absorption provide an alternative to dye molecules, showing great prospects for phototheranostic applications. In this review, the research progress in principally modulating the optical properties of plasmonic nanomaterials, especially affecting parameters such as size, morphology, and surface chemical modification, is introduced. The commonly used plasmonic nanomaterials in the NIR-II window, including noble metals, semiconductors, and heterostructures, are then summarized. In addition, the biomedical applications of these NIR-II plasmonic nanomaterials for PAI and PTT in phototheranostics are highlighted. Finally, the perspectives and challenges for advancing plasmonic nanomaterials for practical use and clinical translation are discussed.

Nanomaterials as multimodal photothermal agents (PTAs) against 'Superbugs'.

Superbugs, also known as multidrug-resistant bacteria, have become a lethal and persistent threat due to their unresponsiveness toward conventional antibiotics. The main reason for this is that superbugs can rapidly mutate and restrict any foreign drug/molecule in their vicinity. Herein, nanomaterial-mediated therapies have set their path and shown burgeoning efficiency toward the ablation of superbugs. Notably, treatment modalities like photothermal therapy (PTT) have shown prominence in killing multidrug-resistant bacteria with their ability to generate local heat shock-mediated hyperthermia in such species. However, photothermal treatment has some serious limitations, such as high cost, complexity, and even toxicity to some extent. Hence, it is important to resolve such shortcomings of PTTs as they provide substantial tissue penetration. This is why multimodal PTTs have emerged and taken over this domain of research for the past few years. In this work, we have summarized and critically reviewed such exceptional works of recent times and provided a perspective to enhance their efficiencies. Profoundly, we discuss the design rationales of some novel photothermal agents (PTAs) and shed light on their mechanisms. Finally, challenges for PTT-derived multimodal therapy are presented, and capable synergistic bactericidal prospects are anticipated.

A single-step plasma method for rapid production of 2D, ferromagnetic, surface vacancy-engineered MoO3-xnanomaterials, for photothermal ablation of cancer.

A rapid, clean plasma-chemical technique is demonstrated here, for cost-effective, synthesis of surface vacancy engineered, 2D, molybdenum-oxide nanomaterials, during a one-step, integrated synthesis-hydrogenation process for biomedical applications. A laminar plasma beam populated with O and H radicals impinges on a molybdenum target, out of which molybdenum-oxide nanomaterials are very rapidly generated with controlled surface O vacancies. 2D, dark-blue coloured, nano-flake/ribbon like MoO3-xis produced maximum up to 194 g h-1, the core of which still remains as stoichiometric molybdenum-oxide. These nanomaterials can get heated-up by absorbing energy from a near-infrared (NIR) laser, which enable them as photothermal therapy (PTT) candidate material for the invasive precision therapy of cancer. The surface defects endows the products with robust ferromagnetism at room temperature conditions (maximum saturation-magnetization: 6.58 emu g-1), which is order of magnitude stronger than most other vacancy engineered nanomaterials. These nanometric metal-oxides are observed to be perfectly compatible in animal physiological environment and easily dispersed in an aqueous solution even without any pre-treatment. The MoO3-xnanomaterials are stable against further oxidation even under prolonged atmospheric exposure.In vitroexperiments confirm that they have ideal efficacy for photothermal ablation of human and murine melanoma cancer at relatively lower dose. Duringin vivoPTT treatments, they may be manipulated with a simple external magnetic field for targeted delivery at the malignant tumours. It is demonstrated that commensurate to the neutralization of the malignant cells, the nanomaterials themselves get self-degraded, which should get easily excreted out of the body.

Potential and Progress of 2D Materials in Photomedicine for Cancer Treatment.

Over the last decades, photomedicine has made a significant impact and progress in treating superficial cancer. With tremendous efforts many of the technologies have entered clinical trials. Photothermal agents (PTAs) have been considered as emerging candidates for accelerating the outcome from photomedicine based cancer treatment. Besides various inorganic and organic candidates, 2D materials such as graphene, boron nitride, and molybdenum disulfide have shown significant potential for photothermal therapy (PTT). The properties such as high surface area to volume, biocompatibility, stability in physiological media, ease of synthesis and functionalization, and high photothermal conversion efficiency have made 2D nanomaterials wonderful candidates for PTT to treat cancer. The targeting or localized activation could be achieved when PTT is combined with chemotherapies, immunotherapies, or photodynamic therapy (PDT) to provide better outcomes with fewer side effects. Though significant development has been made in the field of phototherapeutic drugs, several challenges have restricted the use of PTT in clinical use and hence they have not yet been tested in large clinical trials. In this review, we attempted to discuss the progress, properties, applications, and challenges of 2D materials in the field of PTT and their application in photomedicine.

Nanomaterial-based CT contrast agents and their applications in image-guided therapy.

Computed tomography (CT), a diagnostic tool with clinical application, comprehensive coverage, and low cost, is used in hospitals worldwide. However, CT imaging fails to distinguish soft tissues from normal organs and tumors because their mass attenuation coefficients are similar. Various CT contrast agents have been developed in recent years to improve the sensitivity and contrast of imaging. Here, we review the progress of nanomaterial-based CT contrast agents and their applications in image-guided therapy. The CT contrast agents are classified according to their components; gold (Au)-based, bismuth (Bi)-based, lanthanide (Ln)-based, and transition metal (TM)-based nanomaterials are discussed. CT image-guided therapy of diseases, including photothermal therapy (PPT), photodynamic therapy (PDT), chemotherapy, radiotherapy (RT), gas therapy, sonodynamic therapy (SDT), immunotherapy, starvation therapy, gene therapy (GT), and microwave thermal therapy (MWTT), are reviewed. Finally, the perspectives on the CT contrast agents and their biomedical applications are discussed.

Cancer Immunotherapy Elicited by Immunogenic Cell Death Based on Smart Nanomaterials.

Cancer immunotherapy has been a revolutionary cancer treatment modality because it can not only eliminate primary tumors but also prevent metastases and recurrent tumors. Immunogenic cell death (ICD) induced by various treatment modalities, including chemotherapy, phototherapy, and radiotherapy, converts dead cancer cells into therapeutic vaccines, eliciting a systemic antigen-specific antitumor. However, the outcome effect of cancer immunotherapy induced by ICD has been limited due to the low accumulation efficiency of ICD inducers in the tumor site and concomitant damage to normal tissues. The boom in smart nanomaterials is conducive to overcoming these hurdles owing to their virtues of good stability, targeted lesion site, high bioavailability, on-demand release, and good biocompatibility. Herein, the design of targeted nanomaterials, various ICD inducers, and the applications of nanomaterials responsive to different stimuli, including pH, enzymes, reactive oxygen species, or dual responses are summarized. Furthermore, the prospect and challenges are briefly outlined to provide reference and inspiration for designing novel smart nanomaterials for immunotherapy induced by ICD.