Nanoscale Carbon-Polymer Dots for Theranostics and Biomedical Exploration

In recent years, new carbonized nanomaterials have emerged in imaging, sensing, and various biomedical applications. Published literature shows that carbon dots (CDs) have been explored more extensively than any other nanomaterials. However, its polymeric version, carbon polymer dots (CPDs), did not get much attention. The non-conjugated and single-particle CPDs have all the merits of polymer and CDs, such as photoluminescent properties. The partially carbonized CPDs can be applied like CDs without surface passivation and functionalization. This merit can be further enhanced through the selection of desired precursors and control of carbonization synthesis. CPDs can absorb UV-visible-NIR light and can enhance the photoresponsive chemical and biochemical interactions. This review aims to introduce this area of renewed interest and provide insights into current developments of CPDs nanoparticles and present an overview of chemical, biological, and therapeutic applications.


Introduction
Carbon polymer dots (CPDs) are a member of carbon dots (CDs) and possess a hybrid structure of carbon core attached with organic polymer chains. CPDs are synthesized from different polymer precursors and small organic molecules using controlled canonizations, dehydration, hydrothermal, and condensation ( Figure 1). The controlled carbonizations allow the generation of large functional groups on its surface and play a significant role in maintaining hybrid properties between polymer and CDs. The abundant energy levels in CPDs increase the probability of intersystem crossing (ISC), and their covalently crosslinked framework structures significantly suppress the nonradiative transitions. Moreover, the "core-shell" structures of CPDs are identical compare with a carbon-based and small molecular fluorophore. The center core contributed emission center that retains outer polymer shell [1,2].
The photoluminescent (PL) properties of CPDs are distinguished from organic fluorophores by nonconjugated sub-fluorophores, including C=N, C=O, N=O, C-O, and different hetero-atom containing double (=) bonds. Fortunately, these sub-fluorophores' fluorescence in PCDs can be enhanced through physical immobilization or chemical crosslinking of polymer chains, which is entitled to the enhanced cross-link emission (CEE) effect. The low synthesis cost, unique structures, low toxicity, and excitation-dependent luminescence are among a few of the growing attractive merits of CPDs [3,4].

Carbon Polymer Dot (CPDs), Carbon Dots (CDs) and Polymer Dots (PDs)
The most familiar CDs are low-dimensional carbon-based nanoparticles (NPs). The NPs are typically ~20 nm size and sp2/sp3 hybrid carbon composition. The carbonization reaction in the hydrated media, as well as the precursor source of CDs, contributed to a large number of functional groups on its surface including, amine (-NH2), hydroxyl (-OH), and carboxylic (-COOH) groups. The CDs' surface functional groups can be a conjugated ligand to link other organic and inorganic materials. However, in its polymeric version, the carbon polymer dots (CPDs) belong to a center core carbon with a nonconjugated hybrid polymeric structure. The dominant polymeric parts in CPDs mainly determine the faith of this nanoscale material. Therefore compare to CDs, its hybrid form of CPDs shows better optical and photoluminescence quantum yield (PLQY) [1].
CPDs hold three unique properties. First, the incomplete carbonization results in a low molecular weight chain and many functional groups. Second, the reaction condition in the complex polymerization generates polydispersity on the PCDs structure. Lastly, dehydration and carbonization are attributed to the distinctly cross-linked network structure. On the other hand, the typical polymer dots (PDs) have a shortage of this identical cross-link feature. All of these properties are different compared with un-carbonized PDs and completely carbonized CDs [1,6,7].
In general, the partial carbonizations of polymer precursor sources have generated CPDs (Table 1). Therefore, the level of carbonization determines the functional and structural identity of hybrid PCDs polymer-carbon nanoparticles. The CDs' post-decoration can also reach the CPDs with polymer or organic molecules. The CPDs prepared by post-decoration have possessed the complete core structures of CDs with a clear boundary between the core and polymer shell. The carbon core of CPDs is supported to be the full carbonization core, concretely similar to CDs' core structures. The cores can show intrinsic state or sub-domain state emission, respectively, or a

Carbon Polymer Dot (CPDs), Carbon Dots (CDs) and Polymer Dots (PDs)
The most familiar CDs are low-dimensional carbon-based nanoparticles (NPs). The NPs are typically~20 nm size and sp2/sp3 hybrid carbon composition. The carbonization reaction in the hydrated media, as well as the precursor source of CDs, contributed to a large number of functional groups on its surface including, amine (-NH2), hydroxyl (-OH), and carboxylic (-COOH) groups. The CDs' surface functional groups can be a conjugated ligand to link other organic and inorganic materials. However, in its polymeric version, the carbon polymer dots (CPDs) belong to a center core carbon with a nonconjugated hybrid polymeric structure. The dominant polymeric parts in CPDs mainly determine the faith of this nanoscale material. Therefore compare to CDs, its hybrid form of CPDs shows better optical and photoluminescence quantum yield (PLQY) [1].
CPDs hold three unique properties. First, the incomplete carbonization results in a low molecular weight chain and many functional groups. Second, the reaction condition in the complex polymerization generates polydispersity on the PCDs structure. Lastly, dehydration and carbonization are attributed to the distinctly cross-linked network structure. On the other hand, the typical polymer dots (PDs) have a shortage of this identical cross-link feature. All of these properties are different compared with un-carbonized PDs and completely carbonized CDs [1,6,7].
In general, the partial carbonizations of polymer precursor sources have generated CPDs (Table 1). Therefore, the level of carbonization determines the functional and structural identity of hybrid PCDs polymer-carbon nanoparticles. The CDs' post-decoration can also reach the CPDs with polymer or organic molecules. The CPDs prepared by postdecoration have possessed the complete core structures of CDs with a clear boundary between the core and polymer shell. The carbon core of CPDs is supported to be the full carbonization core, concretely similar to CDs' core structures. The cores can show intrinsic state or sub-domain state emission, respectively, or a semi-crystalline carbon core structure composed of tiny carbon clusters surrounded by polymer frames or a partly dehydrated cross-linking close-knit polymer structure core that can be an ordered carbon skeleton structure [1,8].
The nanoscale carbon core appears like a sub-domain in CPDs, which are considered pi-conjugated graphene (G) and diamond (D) like hybrid structures. The pi-conjugated could also appear like a fullerene structure. As a result, studies show amorphous structural properties of CPDs. In one notable report, the CPDs demonstrated a needle-like shape on the TEM (transmission electron microscopy) [5]. Other reports also show 0.20 nm lattice spacing of CPDs on the high-resolution transmission electron microscopy (HR-TEM). The studies also demonstrated a thin amorphous layer on every side of CPDs. At the same time, the X-ray diffraction patterns showed identical peaks around 18.7 • and interlayer spacing of 0.47 and 0.34 nm, respectively. This could be due to the hybridized structural effects of polymer and carbonized parts. Therefore, sustained optical absorption and long-term aqueous stability of CPDs was demonstrated well suited for biomedical exploration [2,5].
The large surface functional groups and sustain photostability are one of the iconic merits of CPDs. The FT-IR and XPS report in different studies has shown many carbon, nitrogen, and oxygen-containing functional groups. As most of the CPDs synthesize by surface oxidation during pyrolysis, oxygen-containing functional groups dominate. In other literature, it has also been found that CPDs can provide rapid optical response potential for biomedical sciences [5].
The transmission electron microscope (TEM) images usually determine the size of any nanoparticles like carbon-polymer dots and non-carbon dots. The size distribution can be measured using dynamic light scattering (DLS) and surface charge through a zeta sizer. All of these data were used to recognize nanoparticles' size and shape. The differences between CPDs and CDs can be compared in TEM and DLS analysis. In the case of CPDs, the size determined in DLS measurements was bigger than TEM (size) results. The result (larger size) explained the extension of polymeric parts presence on the CPDs in the aqueous-based DLS study. However, such prominent size differences were not noticed in CDs analysis due to lack of polymer moiety [6].
In some cases, the scanning electron microscope (SEM) with energy-dispersive X-ray spectroscopy (EDX) are combined (SEM/EDX) and used to determine the size and elemental composition measurements. Additionally, X-ray photoelectron spectroscopy (XPS), nuclear magnetic resonance (NMR) spectroscopy, and infrared (IR) have provided valuable information about the nature of the composition, either it is carbon-polymer dots or carbon dots. In the XPS analysis, the higher percentages of sp2 type carbon at 284 eV and a π-π* transition peak appeared at 292 eV for the CDs were different identities compare with CPDs. At the 1H-NMR signal, the respective peaks of the precursor (polymer) sources were found to be a presence in the CPDs nanocomposite, but no meaningful (polymeric) peaks were observed in the CDs materials [9,10]. As both are carbon-based nanomaterials, the Raman spectroscopic D and G band can identify the ratio of carbon-carbon single and carbon=carbon double bond [9][10][11].
The incomplete or partial carbonizations of CPDs have molded polymeric merit with many surface functional groups. The chemical functional groups can work as a reactive bridge to, linked with others that are advantageous for requiring modification. Furthermore, the low toxicity and biocompatibility, and simple process-ability are more promising for biological application than organic dyes or inorganic quantum dots (QDs) [11].
The carbon skeleton and surface polymeric functional groups of CPDs have been made identical from a single molecular state. The identical hybrid structures provided synergistic effects for photoluminescence (PL). Many reports believe that sub-fluorophores where extended pi-electron and surface chemistry work together to create an energy gap of the surface state. The new sub-levels on the pi-electronic system with electrons and holes (e/h) pair recombine, which play an essential role in photoluminescence (PL) [3]. The sub-levels on PCDs can be created during synthesis through surface oxidation or others methods.

Current Status and Correlation of Different CPDs
At present, the hydrothermal route has been used to synthesize CPDs from various sources (Table 1). The exothermic reaction of hydrothermal carbonization facilitated the conversion of organic compounds to structured carbons [8,[10][11][12][13][14][15][16]. Both low temperature and high temperature were used in this regard for desired carbonization [19]. The reaction can be stopped in several stages for incomplete elimination of water or carbonization that results from the synthesis of partial carbonized CPDs. Several other studies show the controlled dehydration against carbon sources using the strong acid-assisted synthesis of CPDs [22][23][24]. The solvothermal, microwave heat-based and regulated chemical reactions were used to achieve desired carbonization and synthesis of CPDs [28,33]. At the end of synthesis, centrifugation, dialysis, or electrophoresis were used to separate and purify CPDs. At the same time, the chromatography can be used for the purification of CPDs.
In general, a hydrothermal process, a dehydration reaction, or a microwave-assisted method can be used to synthesize CDs and CPDs. In the case of CPDs synthesis, the reaction condition needs to optimize for the required CPDs. For example, the chemical and fluorescence properties need to evaluate at a different time (5 min, 10 min, 20 min, or 30 min) of dehydration reaction. The exact reaction time that allows required CPDs depends on the nature of the polymer precursor source and the dehydration reaction environment. However, the maximum dehydration at a specific reaction time resulting vanish all polymeric precursors, which results in the CDs [1,3,7]. For example, 1.5 min dehydration of Hyaluronic Acid (HA) by H 2 SO 4 (30N) shown partial carbonized CPDs (Hyaluronic Acid Fluorescent Carbon Nanoparticle) and 10 min dehydration generated CDs (Fluorescent Carbon Nanoparticle). The carbonization of fewer than 1.5 min did not show any noticeable fluorescence, and carbonizations of fewer than 10 min were allowed CPDs formation. The critical point was that the reaction conditions needed to be finely adjusted to get a higher yield and controlled the carbonization reaction [39].
The specific nanoparticles with polymeric hybrid structures have allowed explorations of different promising applications. Both unmodified and modified CPDs including doped CPDs are potential for metal ions sensing. The inherent PL properties showed fluorescence-based detection of different metal ions including, Cr (VI), Co 2+ , and Mn 2+ (Table 2) [28,33,40]. Furthermore, the room-temperature phosphorescence, light-emitting diodes and photocatalysis applications against CPDs are very promising [8,17,31]. Different notable studies demonstrated that polymer-based CPDs could be used as skin sensors to monitor pathophysiological conditions, including cancer [15,25]. In the anti-counterfeit materials, pH probe and photocatalytic exploration of CPDs are among the few areas that get considerable attention [13,14,18]. Moreover, the biocompatibility of CPDs is demonstrated through the hepatobiliary system and kidney eliminations that can work towards in biomedical sciences including, the drug delivery system [33]. Therefore the notable studied confirmed that CPDs are promising for drug (doxorubicin)-loading, Photodynamic Therapy (PDT), and theranostics applications [11,23,24,32].

Bio-Conjugation and Surface Functionalization
CPDs have shown different types of chemical functional groups, including COOH and -OH that can integrate with other materials. For example, CPDs that conjugate therapeutic agents could perform medical imaging and anticancer activity and real-time tracing for diagnosis and therapeutic monitoring. The combined diagnosis and therapeutic, commonly known as theranostic, can be a promising area for CPDs. Additionally, the CPDs integrated nanomaterials can be a potential candidate for thermo-and pH-responsive drug delivery, photo-optical temperature sensing, photothermal and photodynamic therapy, and other biomedical sciences [41]. Therefore, we can expect that many exciting explorations are waiting in the study of the polymeric characteristic of CPDs.
The distinguishing property of CPDs is randomness in polymeric type structure and polydispersity. Due to the mixed presence of polymer chains and carbon clusters during synthesis, it is most analogous to typical polymeric property. The reaction synthesis condition including temperature, time, and pH, determines the nature of CPDs. As a result, variability in structure has been found in its structures. Therefore optical properties are also affected owing to differences in size and morphology [4]. It is imperative in the case of improved quasi-mono-dispersed CPDs.
CPDs have shown a strong absorption band near the UV area and a broad spectrum from visible to NIR region. The hybrid carbon-polymeric structures and polydispersity are mainly responsible for the broad absorption spectrum. In CPDs, the carbonized parts mainly exhibited π-π* type transition while the surface functional groups and lone pair electron contributed n-π* transition. The size-related quantum confinement effects and energy bandgap can be a liable factor of identical light absorption bands. Moreover, the dense carbon parts in the CPDs and different groups could be a reason for generating the energy gap. The size variation due to polydispersity and surface chemistry might combinedly control the characteristic of optical property. As the mechanism of optical absorption of CPDs is still unclear, more studies are required to make satisfactory elusive [4].
The difficulties in determining the mechanism of CPDs' optical absorption properties are mainly because of the large hetero-atom. It is related to carbon-polymer hybrid configuration. Some studies proposed the similarity relation between fluorescent polymer materials and CPDs optical behavior. The fluorescent polymeric materials belong to fluorescent molecules conjugated polymer. The heteroatom like C-O, C-N, and N-O on the fluorescent polymeric materials works like a fluorophore. In this configuration, the polymeric chain works to decrease the energy bandgap resulting emission of fluorescence energy [4,42].

Biomedical and Theranostic Applications of Carbon Polymer Dots (CPDs)
The advancement in low-dimensions nanomaterials drug-carrier has rapidly translated into clinical practice. Interestingly, the one-dimensional (1D) nanomaterials of carbon dots (CDs) are relatively well-explored compared with their polymeric version, carbon polymer dots (CPDs). However, the unique polymeric properties of CPDs nanomaterials make them well-suited for the different biomedical fields. Recent studies have shown that CPDs are potential candidates in biomedical sciences, both as nanocarriers and nanotransducers [43][44][45][46]. CPDs are a potential candidate for the researcher to develop novel functional materials. The conjunctions of required organic and inorganic building moieties into the CPDs have made it more realistic [1]. Furthermore, the unique fabrication of CPDs with other bioactive molecules has been demonstrated in different published reports. Therefore, it is expected that CPDs can be more attractive than carbon dots (CDs) [7,24]. For example, CPDs like CDs could deliver the anticancer drug to its targeted area and perform the theranostic activity ( Figure 2). J. Nanotheranostics 2021, 2, FOR PEER REVIEW 8 nomaterials make them well-suited for the different biomedical fields. Recent studies have shown that CPDs are potential candidates in biomedical sciences, both as nanocarriers and nano-transducers [43][44][45][46]. CPDs are a potential candidate for the researcher to develop novel functional materials. The conjunctions of required organic and inorganic building moieties into the CPDs have made it more realistic [1]. Furthermore, the unique fabrication of CPDs with other bioactive molecules has been demonstrated in different published reports. Therefore, it is expected that CPDs can be more attractive than carbon dots (CDs) [7,24]. For example, CPDs like CDs could deliver the anticancer drug to its targeted area and perform the theranostic activity ( Figure 2). In one notable study, the controlled carbonization method using hyaluronic acid (HA) results from partial-carbonized HA-FCN with remaining HA (Figure 2). Hyaluronic acid (HA) is commonly used in tumor-targeted drug delivery owing to CD-44 receptor binding affinity. The noticeable exploration showed in vivo for targeted delivery and bio-imaging potentials. Moreover, fully carbonized the fluorescent carbon nanoparticle (FCN) from the same sources resulted in a biocompatible bioimaging probe [46]. Further extension of this notable study found HA-FCN conjugated with boronic acid to form diol-linkage with cyclodextrin. Finally, the chemotherapeutic paclitaxel was part of the inclusion complex into HA-FCN conjugated cyclodextrin. Their novel attempts have allowed for controlling drug release in response to extracellular tumor environment (pH) and external-remote photo thermally [47]. These facts have fueled efforts to develop a robust drug delivery system that can bring new hope for cancer treatment.
The most attractive properties of these CPDs for biological applications are the broad absorption of light in the UV-Vis-NIR region, photoluminescence, exceptional photo-response, photosensitized production of singlet oxygen, and vast surface area for the covalent and non-covalent anchoring of diagnostic agents and drugs/DNA/RNA. In one notable study, the controlled carbonization method using hyaluronic acid (HA) results from partial-carbonized HA-FCN with remaining HA (Figure 2). Hyaluronic acid (HA) is commonly used in tumor-targeted drug delivery owing to CD-44 receptor binding affinity. The noticeable exploration showed in vivo for targeted delivery and bio-imaging potentials. Moreover, fully carbonized the fluorescent carbon nanoparticle (FCN) from the same sources resulted in a biocompatible bioimaging probe [46]. Further extension of this notable study found HA-FCN conjugated with boronic acid to form diol-linkage with cyclodextrin. Finally, the chemotherapeutic paclitaxel was part of the inclusion complex into HA-FCN conjugated cyclodextrin. Their novel attempts have allowed for controlling drug release in response to extracellular tumor environment (pH) and external-remote photo thermally [47]. These facts have fueled efforts to develop a robust drug delivery system that can bring new hope for cancer treatment.
The most attractive properties of these CPDs for biological applications are the broad absorption of light in the UV-Vis-NIR region, photoluminescence, exceptional photoresponse, photosensitized production of singlet oxygen, and vast surface area for the covalent and non-covalent anchoring of diagnostic agents and drugs/DNA/RNA. Furthermore, the functionalized CPDs showed promising results in biosensing. In one studied, α-l-Fucosidase (AFu) diseases biomarker was evaluated using hydrolyzate of 4-nitrophenylα-l-fucopyranoside on the functionalized CPDs [48]. Therefore, drug and gene delivery, photothermal or photodynamic therapy, biosensing, and medical imaging are promising areas for CPDs [4,49,50].
The nanoscale based nano-fabrication is a very emerging research area. The typical metal ion sensing required lengthy and complex instrumental spectroscopic techniques. However, the carbonized CPDs have stable optical properties that could be utilized in electrochemistry and wastewater treatment to absorb and separate metal ions. In one notable study, the researcher successfully measured Cu 2+ ions using nano-fabricate CPDs. The low-cost, straightforward, and effective methods in this finding could be extended to other similar platforms ( Figure 3) [51,52].
The nanoscale based nano-fabrication is a very emerging research area. The typical metal ion sensing required lengthy and complex instrumental spectroscopic techniques. However, the carbonized CPDs have stable optical properties that could be utilized in electrochemistry and wastewater treatment to absorb and separate metal ions. In one notable study, the researcher successfully measured Cu 2+ ions using nano-fabricate CPDs. The low-cost, straightforward, and effective methods in this finding could be extended to other similar platforms ( Figure 3) [51,52].
The remarkable optical properties of CPDs and cross-linked polymeric properties have inspired potential applications in biomedical sciences [53,54]. The cytocompatibility and bioimaging merits of CPDs demonstrated on KB (human oral squamous carcinoma) cells. The minimum cytotoxicity against CPDs was shown on the MTT assay. The empirical finding suggested that CPDs could be used in high concentrations in vivo [54,55]. The intravenous injection mouse studies against mouse was exhibited in vivo bioimaging potentiality. The emission wavelength recorded 600 nm in response to 540 nm excitation wavelength that is a potential for fluorescence bioimaging [56]. The targeting drug delivery system (DDS) is crucial for improving tumor area-specific drug release and therapeutic efficacy [57,58]. At present, different light-responsive nanomaterials have been studyied as upcoming anticancer drug carriers. In this platform, the successful targeting with light-responsive nanomaterials could be used as PDT by generating toxic reactive oxygen species (ROS). It could also be used as PTT by producing heat to kill the cancer cells thermally (Figure 3) [32]. The polymer with carbonized CDs in response to excitation light can utilize area-specific cancer therapy. The photo-responsive CPDs could use like CDs for the development of essential therapeutic materials [59,60].
At the same time, photothermal-dependent light-responsive CPDs could be employed in temperature-controlled drug delivery and photothermal chemotherapy [61,62]. In this arena, the inorganic metal oxide nanoparticles and fully carbonized graphene The remarkable optical properties of CPDs and cross-linked polymeric properties have inspired potential applications in biomedical sciences [53,54]. The cytocompatibility and bioimaging merits of CPDs demonstrated on KB (human oral squamous carcinoma) cells. The minimum cytotoxicity against CPDs was shown on the MTT assay. The empirical finding suggested that CPDs could be used in high concentrations in vivo [54,55]. The intravenous injection mouse studies against mouse was exhibited in vivo bioimaging potentiality. The emission wavelength recorded 600 nm in response to 540 nm excitation wavelength that is a potential for fluorescence bioimaging [56].
The targeting drug delivery system (DDS) is crucial for improving tumor area-specific drug release and therapeutic efficacy [57,58]. At present, different light-responsive nanomaterials have been studyied as upcoming anticancer drug carriers. In this platform, the successful targeting with light-responsive nanomaterials could be used as PDT by generating toxic reactive oxygen species (ROS). It could also be used as PTT by producing heat to kill the cancer cells thermally (Figure 3) [32]. The polymer with carbonized CDs in response to excitation light can utilize area-specific cancer therapy. The photo-responsive CPDs could use like CDs for the development of essential therapeutic materials [59,60].
At the same time, photothermal-dependent light-responsive CPDs could be employed in temperature-controlled drug delivery and photothermal chemotherapy [61,62]. In this arena, the inorganic metal oxide nanoparticles and fully carbonized graphene oxide, CDs, and carbon nanotubes are well-recognized materials; however, CPDs did get much recognition in the research community [63][64][65][66][67][68]. For instance, the polymeric nature of CPDs can load maximum drug on its lengthy chain to perform a light-triggered controlled drug release upon irradiation.
Photo-responsive CPDs are also potentially light harvesting; with potential for photocatalysis application [69]. Studies showed presences of abundant functional groups can regulate electron-donating or withdrawing function. Therefore, the -NH2 or -COOH functional groups containing CPDs act as cathode or anode interlayers for the development of polymer solar cells (PSCs) [70].

Perspective and Future Directions
Carbon polymer dots (CPDs) are a new variant of well-known carbon dots (CDs). The distinctive polymer/carbon hybrid structure, low degree of carbonization, nonconjugated fluorescent polymeric nature, and high degree of crosslinking have made CPDs the most promising candidate in other biomedical explorations. CPDs gained tremendous attention in the biology field because of high water solubility, high quantum yield, low toxicity, surface functionalization, and accessible synthesis methods. The synthesis methods of CPDs with changing morphology are still unclear due to the lack of systematic structure characteristics and complex polymer/carbon hybrid features. However, the controlled synthesis of desired CPDs can contribute to bioimaging, biosensing, biomedicine, and drug delivery systems. The hybrid polymeric nature of CPDs provided easy surface functionalization according to desire properties like blending, grafting, and covalent bonding with the functional molecule, polymer, or inorganic materials. It will explore the enormous possibility of targeted drug delivery, phototherapy, medical bioimaging, and small molecule and ion detection. The previous researches of photoresponsive CPDs are very promising because of small sizes, functionalization potentiality, and the ability to introduce multiple therapeutic agents on its surface. A collective effort from nanotechnology has required the development of cancer theranostic to overcome the hurdle of translating photoresponsive CPDs.

Conclusions
The cooperative effort from nanotechnology needs to synthesize carbon polymer dots (CPDs) for biomedical application. Though scale-up synthesis and purification of CPDs are still challenging, the photophysical and biocompatible properties are up-and-coming. Moreover, different bioactive therapeutic can be anchored to its surface to develop a brandnew drug delivery system (DDS). The combined therapeutic with diagnostic nanoparticles (NPs) known as theranostics NPs, set a potential site for CPDs. The exploration of CPDs is still in the early stage; however, the preliminary works are so attractive to shift the paradigm of traditional NPs. Therefore, the unique properties of CPDs are expected to translate their potential role clinically.