Antibody‐based cancer therapy, one of the most significant therapeutic strategies, has achieved considerable success and progress over the past decades. Nevertheless, obstacles including limited ...tumor penetration, short circulation half‐lives, undesired immunogenicity, and off‐target side effects remain to be overcome for the antibody‐based cancer treatment. Owing to the rapid development of nanotechnology, antibody‐containing nanomedicines that have been extensively explored to overcome these obstacles have already demonstrated enhanced anticancer efficacy and clinical translation potential. This review intends to offer an overview of the advancements of antibody‐incorporated nanoparticulate systems in cancer treatment, together with the nontrivial challenges faced by these next‐generation nanomedicines. Diverse strategies of antibody immobilization, formats of antibodies, types of cancer‐associated antigens, and anticancer mechanisms of antibody‐containing nanomedicines are provided and discussed in this review, with an emphasis on the latest applications. The current limitations and future research directions on antibody‐containing nanomedicines are also discussed from different perspectives to provide new insights into the construction of anticancer nanomedicines.
A comprehensive review on the advancements of antibody‐incorporated nanomedicines for cancer therapy is offered. Diverse functionalization strategies, antibody formats, and cancer‐associated antigens are introduced and discussed, with an emphasis on their latest applications in antibody‐incorporated nanotherapeutics. The current limitations and future research directions on antibody‐containing nanomedicines are also proposed.
Objectives
MicroRNAs (miRNAs) are a type of small noncoding RNA employed by the cells for gene regulation. A single miRNA, typically 22 nucleotides in length, can regulate the expression of numerous ...genes. Over the past decade, the study of miRNA biology in the context of cancer has led to the development of new diagnostic and therapeutic opportunities.
Key findings
MicroRNA dysregulation is commonly associated with cancer, in part because miRNAs are actively involved in the mechanisms like genomic instabilities, aberrant transcriptional control, altered epigenetic regulation and biogenesis machinery defects. MicroRNAs can regulate oncogenes or tumour suppressor genes and thus when altered can lead to tumorigenesis. Expression profiling of miRNAs has boosted the possibilities of application of miRNAs as potential cancer biomarkers and therapeutic targets, although the feasibility of these approaches will require further validation.
Summary
In this review, we will focus on how miRNAs regulate tumour development and the potential applications of targeting miRNAs for cancer therapy.
Immuno‐oncology therapies have been approved for various solid tumors; however, the high cost of these treatments and their potential toxicities require a thorough assessment of their risks and ...benefits. Collection of data directly from patients through patient‐reported outcome instruments can improve the precision and reliability of adverse event detection, assess tolerability of adverse events, and provide an evaluation of health‐related quality of life (HRQOL) changes from immuno‐oncology therapies. There is robust development in HRQOL tools specifically for patients treated with immuno‐oncology agents. This review examines the history and basic concepts of HRQOL and patient‐reported outcome assessments commonly used in oncological trials, highlighting the strengths and weaknesses of current approaches when applied to immunotherapies, as well as some of the current efforts to develop tools for this field and opportunities for future research.
Lay Summary
Immuno‐oncology (IO) therapies are costly and carry potential toxicities known as immune‐related adverse events.
Evaluation of health‐related quality of life (HRQOL) can impact the risk‐benefit assessment of IO therapies.
Integration of HRQOL end points and patient‐reported outcome data for IO therapies are urgently needed.
Ongoing robust development of patient‐reported outcome tools specific to IO therapies are currently underway and will permit the evaluation of HRQOL for IO agents.
Improvement in precision and reliability of HRQOL evaluation will enhance the ultimate true value of these expensive and effective drugs.
The evaluation of patients' health‐related quality of life (HRQOL) affects the risk‐benefit assessment of immuno‐oncology therapies. The integration of HRQOL end points and patient‐reported outcome (PRO) data for immuno‐oncology therapies—with PRO tools designed specifically for these therapies—is urgently needed.
Elevated intracellular reactive oxygen species (ROS) and antioxidant defense systems have been recognized as one of the hallmarks of cancer cells. Compared with normal cells, cancer cells exhibit ...increased ROS to maintain their malignant phenotypes and are more dependent on the “redox adaptation” mechanism. Thus, there are two apparently contradictory but virtually complementary therapeutic strategies for the regulation of ROS to prevent or treat cancer. The first strategy, that is, chemoprevention, is to prevent or reduce intracellular ROS either by suppressing ROS production pathways or by employing antioxidants to enhance ROS clearance, which protects normal cells from malignant transformation and inhibits the early stage of tumorigenesis. The second strategy is the ROS‐mediated anticancer therapy, which stimulates intracellular ROS to a toxicity threshold to activate ROS‐induced cell death pathways. Therefore, targeting the regulation of intracellular ROS‐related pathways by small‐molecule candidates is considered to be a promising treatment for tumors. We herein first briefly introduce the source and regulation of ROS, and then focus on small molecules that regulate ROS‐related pathways and show efficacy in cancer therapy from the perspective of pharmacophores. Finally, we discuss several challenges in developing cancer therapeutic agents based on ROS regulation and propose the direction of future development.
Compared to noncancerous cells, tumor cells usually harbor elevated reactive oxygen species (ROS). Therefore, targeting regulation of ROS homeostasis in cancer cells has been recognized a promising approach in cancer prevention or treatment depending on the stage of tumor development.
•Stereospecific interactions between chiral AuNCs and proteins resulted different size distributions of L/D-NCs in cell medium.•D-AuNCs exhibited lower cytotoxicity compared with L-AuNCs.•The ...radiosensitizating efficiency of D-AuNC was higher than L-AuNC.•Chirality of metal clusters has significant effect on radiotherapy.
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Due to the homo-chirality preference of human body to most of chiral species, synthesizing enantiopure drugs and investigating the pharmacological activity of each enantiomer would have great meaning. However, the influence of chirality at nanoscale on the ability to enhance radiotherapy has not been studied. Herein, a pair of enantiomeric alkynyl-protected L/D-Au10(C13H17O5)10 nanoclusters (L/D-AuNCs) with strong chirality (g value up to 3.6 × 10-3) and circular polarization luminescence (glum ≈ 3 × 10-3) are prepared and applied as radiosensitizers. As a consequence, D-AuNCs exhibit better radiosensitization effect in vitro, which is confirmed by research on mechanisms including reactive oxygen species (ROS) burst mediated DNA breakage, cell cycle arrest and up-regulation of apoptotic protein expression. In vivo antitumor studies manifest that tumors treated with D-AuNCs and X-ray show a volume decrease of 51% compared with X-ray (4 Gy) only group. This work not only enriches the family of gold-based nano-radiosensitizers, but also further proves the significance of chirality in biomedicine.
2D nanomaterials with unique nanosheet structures, large surface areas, and extraordinary physicochemical properties have attracted tremendous interest. In the area of nanomedicine, research on ...graphene and its derivatives for diverse biomedical applications began as early as 2008. Since then, many other types of 2D nanomaterials, including transition metal dichalcogenides, transition metal carbides, nitrides and carbonitrides, black phosphorus nanosheets, layered double hydroxides, and metal–organic framework nanosheets, have been explored in the area of nanomedicine over the past decade. In particular, a large surface area makes 2D nanomaterials highly efficient drug delivery nanoplatforms. The unique optical and/or X‐ray attenuation properties of 2D nanomaterials can be harnessed for phototherapy or radiotherapy of cancer. Furthermore, by integrating 2D nanomaterials with other functional nanoparticles or utilizing their inherent physical properties, 2D nanomaterials may also be engineered as nanoprobes for multimodal imaging of tumors. 2D nanomaterials have shown substantial potential for cancer theranostics. Herein, the latest progress in the development of 2D nanomaterials for cancer theranostic applications is summarized. Current challenges and future perspectives of 2D nanomaterials applied in nanomedicine are also discussed.
2D nanomaterials with their unique nanosheet structure, large surface area, and extraordinary physicochemical properties have attracted tremendous interest for application in many different fields including nanomedicine in recent years. The recent progress in the development of different classes of 2D nanomaterials in biomedicine, especially for cancer theranostic applications, is summarized.
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•Recent advances in metal–organic frameworks (MOFs) as drug carriers are discussed.•Encapsulation and controlled release of drugs by means of MOFs are reviewed.•Therapeutic ...applications of various MOFs are demonstrated.•Cutaneous treatment and controlled release of caffeine through MOFs are presented.•Applications of MOFs in cosmetics are discussed.
Metal-organic frameworks (MOFs) have grabbed attention over the past decades, because of their properties and applications in several areas. MOFs are a class of coordination polymers that are formed through metal ion/clusters and organic linkers. A wide range of metal centers and organic linkers can be utilized to construct one-, two-, or three-dimensional structures. They exhibit excellent features including adjustable pore sizes, great surface area, and various functionalities and are applied in several areas, energy storage, CO2 adsorption, catalysis, cosmetics, drug storage and delivery. Because of low cytotoxicity, high biodegradability, and high biocompatibility, MOFs are suitable for biomedical applications. Besides, due to mentioned properties, MOFs can be used in cosmetics including skin disease treatments, controlled release of fragrances, storage and release of caffeine, and determination of parabens in cosmetic creams too. The utilization of suitable carriers to deliver the drugs in the body effectively is one of the main challenges in biomedicine. A large number of the current carriers reveal rapid drug release and poor loading. Since MOFs demonstrate good loading of drug in their pores, they are suitable carriers in drug delivery system. Owing to tunable pores size and large surface area, MOFs are good choice in the cosmetic industry. In the present review, the MOFs applications in drug delivery and cosmetics are considered and evaluated.
Fenton reaction‐mediated chemodynamic therapy (CDT) can kill cancer cells via the conversion of H2O2 to highly toxic HO•. However, problems such as insufficient H2O2 levels in the tumor tissue and ...low Fenton reaction efficiency severely limit the performance of CDT. Here, the prodrug tirapazamine (TPZ)‐loaded human serum albumin (HSA)–glucose oxidase (GOx) mixture is prepared and modified with a metal–polyphenol network composed of ferric ions (Fe3+) and tannic acid (TA), to obtain a self‐amplified nanoreactor termed HSA–GOx–TPZ–Fe3+–TA (HGTFT) for sustainable and cascade cancer therapy with exogenous H2O2 production and TA‐accelerated Fe3+/Fe2+ conversion. The HGTFT nanoreactor can efficiently convert oxygen into HO• for CDT, consume glucose for starvation therapy, and provide a hypoxic environment for TPZ radical‐mediated chemotherapy. Besides, it is revealed that the nanoreactor can significantly elevate the intracellular reactive oxygen species content and hypoxia level, decrease the intracellular glutathione content, and release metal ions in the tumors for metal ion interference therapy (also termed “ion‐interference therapy” or “metal ion therapy”). Further, the nanoreactor can also increase the tumor’s hypoxia level and efficiently inhibit tumor growth. It is believed that this tumor microenvironment‐regulable nanoreactor with sustainable and cascade anticancer performance and excellent biosafety represents an advance in nanomedicine.
A self‐amplified nanoreactor termed HSA–GOx–TPZ–Fe3+–TA (HGTFT), consisting of human serum albumin, glucose oxidase, tirapazamine (TPZ), Fe3+, and tannic acid (TA), is prepared for sustainable and cascade cancer therapy with exogenous H2O2 production and TA‐accelerated Fe3+/Fe2+ conversion. The nanoreactor can convert oxygen into HO• for chemodynamic therapy, consume glucose for starvation therapy, and provide a hypoxic environment for TPZ radical‐mediated chemotherapy.
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