Nanoparticles-based phototherapy systems for cancer treatment : Current status and clinical potential

Remarkable progress in phototherapy has been made in recent decades, due to its non-invasiveness and instant therapeutic efficacy. In addition, with the rapid development of nanoscience and nanotechnology, phototherapy systems based on nanoparticles or nanocomposites also evolved as an emerging hotspot in nanomedicine research, especially in cancer. In this review, first we briefly introduce the history of phototherapy, and the mechanisms of phototherapy in cancer treatment. Then, we summarize the representative development over the past three to five years in nanoparticle-based phototherapy and highlight the design of the innovative nanoparticles thereof. Finally, we discuss the feasibility and the potential of the nanoparticle-based phototherapy systems in clinical anticancer therapeutic applications, aiming to predict future research directions in this field. Our review is a tutorial work, aiming at providing useful insights to researchers in the field of nanotechnology, nanoscience and cancer.Peer reviewe

Remotely Activated Nanoparticles for Anticancer Therapy

The present review highlights the importance of remotely activated nanoparticles for anticancer purposes.For each physical input, we present its possible active synergy with several nanomaterials.We report examples and the mechanism of action when clarified.Clinical trials involving remotely triggered nanoparticles are discussed. Cancer has nowadays become one of the leading causes of death worldwide. Conventional anticancer approaches are associated with different limitations. Therefore, innovative methodologies are being investigated, and several researchers propose the use of remotely activated nanoparticles to trigger cancer cell death. The idea is to conjugate two different components, i.e., an external physical input and nanoparticles. Both are given in a harmless dose that once combined together act synergistically to therapeutically treat the cell or tissue of interest, thus also limiting the negative outcomes for the surrounding tissues. Tuning both the properties of the nanomaterial and the involved triggering stimulus, it is possible furthermore to achieve not only a therapeutic effect, but also a powerful platform for imaging at the same time, obtaining a nano-theranostic application. In the present review, we highlight the role of nanoparticles as therapeutic or theranostic tools, thus excluding the cases where a molecular drug is activated. We thus present many examples where the highly cytotoxic power only derives from the active interaction between different physical inputs and nanoparticles. We perform a special focus on mechanical waves responding nanoparticles, in which remotely activated nanoparticles directly become therapeutic agents without the need of the administration of chemotherapeutics or sonosensitizing drugs. [Figure not available: see fulltext.

Biomaterial-based platforms for modulating immune components against cancer and cancer stem cells

Immunotherapy involves the therapeutic alteration of the patient's immune system to identify, target, and eliminate cancer cells. Dendritic cells, macrophages, myeloid-derived suppressor cells, and regulatory T cells make up the tumor microenvironment. In cancer, these immune components (in association with some non-immune cell populations like cancer-associated fibroblasts) are directly altered at a cellular level. By dominating immune cells with molecular cross-talk, cancer cells can proliferate unchecked. Current clinical immunotherapy strategies are limited to conventional adoptive cell therapy or immune checkpoint blockade. Targeting and modulating key immune components presents an effective opportunity. Immunostimulatory drugs are a research hotspot, but their poor pharmacokinetics, low tumor accumulation, and non-specific systemic toxicity limit their use. This review describes the cutting-edge research undertaken in the field of nanotechnology and material science to develop biomaterials-based platforms as effective immunotherapeutics. Various biomaterial types (polymer-based, lipid-based, carbon-based, cell-derived, etc.) and functionalization methodologies for modulating tumor-associated immune/non-immune cells are explored. Additionally, emphasis has been laid on discussing how these platforms can be used against cancer stem cells, a fundamental contributor to chemoresistance, tumor relapse/metastasis, and failure of immunotherapy. Overall, this comprehensive review strives to provide up-to-date information to an audience working at the juncture of biomaterials and cancer immunotherapy. Statement of significance: Cancer immunotherapy possesses incredible potential and has successfully transitioned into a clinically lucrative alternative to conventional anti-cancer therapies. With new immunotherapeutics getting rapid clinical approval, fundamental problems associated with the dynamic nature of the immune system (like limited clinical response rates and autoimmunity-related adverse effects) have remained unanswered. In this context, treatment approaches that focus on modulating the compromised immune components within the tumor microenvironment have garnered significant attention amongst the scientific community. This review aims to provide a critical discussion on how various biomaterials (polymer-based, lipid-based, carbon-based, cell-derived, etc.) can be employed along with immunostimulatory agents to design innovative platforms for selective immunotherapy directed against cancer and cancer stem cells

Synthesis and characterization of ZnO-based/derived nanoparticles as promising photocatalysts

Biocompatibility and the ability to create tumor-killing reactive oxygen species have drawn increasing attention to zinc oxide (ZnO) based/derived nanoparticles for photodynamic treatment. There are several variables that may affect the performance of ZnO-based NPs in PDT that can be manipulated by doping and compositing. Among these variables are the charge separation, the absorption potential, and the bandgap engineering. In this thesis, we reviewed designed and developed improved photodynamic performance ZnO based/derived nanoparticles

Delivery of Molecules Using Nanoscale Systems for Cancer Treatment and/or Diagnosis

This book focuses on how nanoscale systems can be used to deliver molecules to help with cancer management. It provides a broad overview of some of the key strategies for nanocarrier design. These strategies are brought together by the wide compositional variety of these systems and the diversity of molecules that may be carried. Additionally, functionalization strategies, codelivery, and combination with other treatment modalities highlight a very active research field

Nanoparticle-based immunotherapeutics: from the properties of nanocores to the differential effects of administration routes

The engagement with the immune system is one of the main cornerstones in the development of nanotechnologies for therapy and diagnostics. Recent advances have made possible the tuning of features like size, shape and biomolecular modifications that influence such interactions, however, the capabilities for immune modulation of nanoparticles are still not well defined and exploited. This review focuses on recent advances made in preclinical research for the application of nanoparticles to modulate immune responses, and the main features making them relevant for such applications. We review and discuss newest evidence in the field, which include in vivo experiments with an extensive physicochemical characterization as well as detailed study of the induced immune response. We emphasize the need of incorporating knowledge about immune response development and regulation in the design and application of nanoparticles, including the effect by parameters such as the administration route and the differential interactions with immune subsetsThe authors thank the financial support of the European Research Council (starting grant #950421), the European Union (INTERREG V-A Spain–Portugal #0624_2IQBIONEURO_6_E, NextGeneration EU/PRTR and ERDF; H2020-FET-Open grant agreement No. 899612), the MCIN/AEI (PID2020-119206RB-I00, PID2020-119479RA-I00, PID2019-111218RB-I00, RYC-2017-23457, RYC-2019-028238-I and RYC2021‐034576‐I), and the Xunta de Galicia (ED431F 2021/02, 2021-CP090, ED431C 2022/018, and Centro Singular De Investigación de Galicia Accreditation 2019–2022 #ED431G 2019/03). This project was also supported by the ISCIII, under the framework of EuroNanoMed III_2020 (AC20/00041, PLATMED)S

Paradox Role of Oxidative Stress in Cancer

Reactive oxygen species (ROS) are produced by healthy cells and are maintained at physiological levels by antioxidant systems. However, when ROS increase in number, a condition of oxidative stress occurs, leading to many human diseases, including cancer. The relationship between oxidative stress and cancer is complex since ROS play a double-edged role in cancer development and under therapy response. This paradox represents a great challenge for researchers and needs to be investigated. The articles collected in this Special Issue can help to clarify the role of ROS modulation in cancer prevention and treatment, and to dissect the molecular mechanisms underlying its paradoxical role in order to counteract carcinogenesis or enhance sensitivity to anticancer therapy

Towards principled design of cancer nanomedicine to accelerate clinical translation

Nanotechnology in medical applications, especially in oncology as drug delivery systems, has recently shown promising results. However, although these advances have been promising in the pre-clinical stages, the clinical translation of this technology is challenging. To create drug delivery systems with increased treatment efficacy for clinical translation, the physicochemical characteristics of nanoparticles such as size, shape, elasticity (flexibility/rigidity), surface chemistry, and surface charge can be specified to optimize efficiency for a given application. Consequently, interdisciplinary researchers have focused on producing biocompatible materials, production technologies, or new formulations for efficient loading, and high stability. The effects of design parameters can be studied in vitro, in vivo, or using computational models, with the goal of understanding how they affect nanoparticle biophysics and their interactions with cells. The present review summarizes the advances and technologies in the production and design of cancer nanomedicines to achieve clinical translation and commercialization. We also highlight existing challenges and opportunities in the field

Application of Nanomaterials in Biomedical Imaging and Cancer Therapy

To mark the recent advances in nanomaterials and nanotechnology in biomedical imaging and cancer therapy, this book, entitled Application of Nanomaterials in Biomedical Imaging and Cancer Therapy includes a collection of important nanomaterial studies on medical imaging and therapy. The book covers recent works on hyperthermia, external beam radiotherapy, MRI-guided radiotherapy, immunotherapy, photothermal therapy, and photodynamic therapy, as well as medical imaging, including high-contrast and deep-tissue imaging, quantum sensing, super-resolution microscopy, and three-dimensional correlative light and electron microscopy. The significant research results and findings explored in this work are expected to help students, researchers and teachers working in the field of nanomaterials and nanotechnology in biomedical physics, to keep pace with the rapid development and the applications of nanomaterials in precise imaging and targeted therapy

Nanocatalytic CePO4·H2O (Rhabdophane): Mitochondrial-Targeting, Cell-Discriminative, ROS-Mediated Cancer Therapy

Nanocatalytic tumor therapies involve established strategies to increase the concentration of endogenous oxygen species (ROS) H2O2 to cytotoxic levels. These strategies are based on increasing the ROS levels through stimuli from drugs, the action of ROS-producing agents, and nanoparticulate catalysis. However, these techniques frequently are indiscriminatory, being cytotoxic to diseased cells and normal cells alike, leading to significant unwanted side-effects. The present work reports a new paradigm strategy based upon the catalytic action of a cell-discriminative, ROS-mediating, autophagy-suppressive nanoparticle, which is CePO4·H2O (rhabdophane). CePO4·H2O nanoparticles were synthesised using CeNO3·6H2O precipitated in an aqueous solution of sodium tripolyphosphate (STPP) at room temperature. The nanoparticles were well crystallised, equiaxed (~10-35 nm), of positive surface charge, and of general valence ratio 〖"Ce" 〗_"0.8" ^"3+" 〖"Ce" 〗_"0.2" ^"4+" 〖"PO" 〗_"4.1" . Materials characterisation involved particuological (hydrodynamic particle size, surface area, zeta potential), mineralogical (X-ray diffraction, laser Raman microspectroscopy), chemical (X-ray photoelectron spectroscopy), structural (Fourier transform infrared spectroscopy), and microstructural (transmission electron microscopy) analyses. Biological characterisation involved examination of the effects on HT-1080 fibrosarcoma cells and MRC-5 normal fibroblasts in terms of cellular interactions (cell viability by MTT assay), cellular uptake and trafficking (confocal laser scanning microscopy, biological transmission electron microscopy, flow cytometry), ROS generation (confocal laser scanning microscopy, flow cytometry), apoptosis (annexin V-FITC assay), gene expression (q-RT-PRC), and protein expression (western blot analyses). The key observations and conclusions from the biological evaluation are as follows: Discriminative Cytotoxicity: CePO4·H2O nanoparticles are the first to exhibit discriminative cytotoxicity: At 24 h, fibrosarcoma HT-1080 cell viability is ~10% but MRC-5 normal cell viability is ~45%. Discriminative Uptake: CePO4·H2O nanoparticles are the first, without the use of a targeting ligand, to be internalized readily by cancer cells but scarcely by normal cells. Self-Targeting: CePO4·H2O nanoparticles are trafficked toward the mitochondrial environment and possibly the converse trafficking. Mitochondrial Starvation: The preceding proximity between CePO4·H2O nanoparticles and cancer cell leads to increased phosphate concentration in the cellular environment, the concentration gradient of which effectively starves the mitochondria, leading to mitochondrial stress and dysfunction. Discriminative ROS Generation: CePO4·H2O nanoparticles are the first to demonstrate elevated cellular ROS in cancer cells by multiple mechanisms while normal cells exhibit only a low level of such elevation. Autophagy Suppression: CePO4·H2O nanoparticles suppress autophagy, thereby increasing cellular stress and suppressing cancer cell survival, thus offering a complement to mitochondrial starvation. Redox Switching: CePO4·H2O nanoparticles are the first nonmetallic nanoparticles to balance redox switching through simple electronic charge compensation rather than more complex ionic charge compensation. Biocompatibility: As hydrated phosphates, CePO4·H2O nanoparticles are more biocompatible than metals or oxides, suggesting greater feasibility of renal clearance. These advantages derive from the key role of the redox and defect equilibria arising from the oxidation reaction Ce3+ → Ce4+ + e′, which is induced by the acidic pH environment of the cancer call versus the stability of the Ce3+ valence in the basic pH environment of the normal cell. The former both elevates the ROS level and disrupts the electron transfer chain. Ultimately, the suppression of the proliferation of cancer cells derives from the cross-talk involving cellular ROS elevation, autophagy suppression, and their mitochondrial control