INTRODUCTION
Cancer is one of the most serious diseases affecting public health globally because of its high incidence and fatality rate. The inability to target and direct medications to the cancer cells specifically limits the capabilities of present technologies for the diagnosis and treatment of tumors. It is urgently necessary to get over these biological constraints in cancer diagnosis and treatment by developing novel tumor-targeted techniques[1]. Tumor immunotherapy has attracted much attention owing to its efficient targeting and lasting curative effect. Unlike previous surgical excision, chemotherapy, and radiotherapy, tumor immunotherapy is developed to activate the immune system of patients and is hoped to utilize their own immune function to kill cancer cells[2]. In physiological conditions, the immune system identifies foreign substances or abnormal cells and then neutralizes these to protect metabolic homeostasis and health in humans. However, some pathological conditions, especially cancer, would disturb this homeostasis[3]. On the one hand, the surviving cancer cells exhibit lower immunogenicity after undergoing a long-term mutation, on the other hand, the cancer cells would construct a special tumor microenvironment that reduces the inflammatory response of immune cells and escape the immune surveillance[4, 5]. In immunotherapy, macrophages and dendritic cells (DCs) have important roles in the direct recognition of a mutant cell[6]. They phagocytose mutant cells and secrete a plethora of pro-inflammatory mediators that can initiate the inflammatory cascade and present antigens to T cells[6, 7]. This initiates the adaptive immune response and further stimulates T cell division, proliferation, and maturation. Some mature T cells differentiate into memory T cells that retain antigen memory and respond quickly to antigen re-entry, while the majority differentiate into effector cells with immune effects, such as regulatory T cells that produce cytokines to regulate immune response, natural killer (NK) T cells that target and kill foreign cells, and effector T cells that stimulate B-lymphocyte proliferation and antibody production[4, 8, 9]. Over the last few years, increasing biomedical research have indicated the potential of nanomaterials in modulating the immune response[8, 10]. Biomaterials alone, or conjugated with specific biomolecules, can be used to directly regulate the immune system, hence providing new approaches for the enhancement of tumor immunotherapy[4, 11].
Carbon dots (CDs) are fluorescent carbon nanomaterials with a size of less than 10 nm and are composed of graphitizedsp 2 carbon nuclei and shells containing amino, carboxyl, and hydroxyl groups on the surface[12]. In recent years, as a new type of carbon-based nanomaterial, CDs have drawn considerable scientific attention for their distinctive optical properties, low cost, eco-friendliness, the abundance of functional groups, high stability, and electron mobility[13]. Because of their good photoluminescence (PL), high quantum yield (QY), low toxicity, small size, and appreciable biocompatibility, they are used in a variety of fields, including the fields of biomedicine, catalysis, optoelectronics, and anticounterfeiting[14]. The fluorescence excitation and emission wavelength falling within the biological transparency window (650–900 nm) is always one of the major research directions in CDs[15]. There are two benefits to using the near-infrared (NIR) region as the excitation wavelength for fluorescence imaging or photochemical reactions[16]. First, compared to UV-visible light, NIR light can penetrate deeper and gather richer tissue information because it scatters and absorbs less when it comes into contacting with skin and tissue. Second, because the organism emits primarily blue or green fluorescence, NIR light can reduce the interference from spontaneous background fluorescence and enhance the imaging signal-to-noise ratio[15, 16]. So far, there have been recent cases of visible absorption and emission in the NIR range, making CDs attractive agents for biological applications[17]. Their unique fluorescent features, in particular, have fostered their widespread use in a variety of life science domains, including bio-sensing and bio-imaging[18]. In addition to their multicolored emission, tunable optical properties, and outstanding photostability, CDs can also be used as efficient tools for tumor therapy owing to their easy surface functionalization and excellent biocompatibility[14, 19]. On the one side, CDs can be employed as phototherapy agents, including photodynamic therapy (PDT) and photothermal therapy (PTT)[20, 21]. On the other side, the rational design would confer CDs the properties of nanoenzymes or chemotherapeutic agents involved in tumor chemodynamic therapy (CDT)[22]. However, each traditional treatment has its limitations and drawbacks. With a view toward more accurate and effective cancer treatment, collaborative treatments with immunotherapy are becoming increasingly attractive in current CDs research[4].
Tumor immunotherapy mainly includes nonspecific immunotherapy, monoclonal antibody immunotherapy, adoptive immunotherapy, and vaccine therapy[3]. In this mini-review, we will congregate and systematically discuss the relevant research available presently, regarding the application of CDs in tumor immunotherapy. The review collects the related immunotherapy applications of CDs in PDT, PTT, CDT, vaccine, and immunoadjuvant in recent years (Scheme 1). And then, we conclude the current situation of CDs in tumor immunotherapy, together with some challenges and prospects that remain in immunotherapy.