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.