In recent years, fiber optic technology, as a representative optical technology, has demonstrated more possible strategies for cancer theranostics with high sensitivity, minimal invasiveness, anti-electromagnetism, multiplexing, and high machinability^[1–4]. Fiber optic devices can directly approach deep lesions and further achieve tumor sensing^[5], photothermal therapy (PTT)^[6], photodynamic therapy (PDT)^[7], and light-controlled drug delivery and release^[8–11]. Due to clinical needs, integrating detection and therapeutic functions into a single fiber is a prevailing trend and is highly important for minimally invasive interventions, multiplexing, and spatiotemporal operability.

However, the materials that provide therapeutic functions for optical fibers often affect the fiber sensing capabilities, resulting in challenges for the current applications of all-in-one fiber theranostics. For example, graphene shows excellent photothermal effects, but its efficient energy transfer, surface defects, and π-π interactions result in fluorescence quenching^[12,13]. Similar materials, including graphene oxide^[14] and carbon nanotubes^[15], have demonstrated difficulty in achieving high sensitivity in sensing performance while enabling PTT. Therefore, the selection of materials is crucial for functionalizing optical fibers to achieve fiber photothermal effects while ensuring fluorescence efficiency.

Black phosphorus (BP), due to its unique electronic and physical properties, is a promising material for addressing the aforementioned issues. BP exhibits exceptionally high photothermal conversion efficiency, indicating that it can achieve higher temperatures and a broader range of PTT by safe and low-power laser irradiation. Currently, therapies based on BP, including PDT/PTT/immunotherapy^[16], photothermal-enhanced immunotherapy^[17], and infrared imaging-guided PTT^[18], have been developed. Importantly, in addition to its advantages in PTT applications, BP has low fluorescence quenching due to its direct bandgap, fewer surface defects, chemical stability, and weak π-π interactions, making it favorable for fiber fluorescence sensing^[19,20]. Additionally, as mentioned in previous research, gold nanostars (AuNS) can further enhance the fluorescence signal during detection^[21]. Therefore, combining BP with AuNS can provide a more efficient all-in-one strategy for fiber medicine compared to previous research^[22–24]. Furthermore, the application of hydrogels provides a convenient method for immobilizing these materials on optical fibers^[25].

In this study, BP is innovatively developed for fiber theranostics due to its non-interference with fluorescence sensing and controllable high photothermal effect. In this study, a fiber optic sensor based on hydrogel-encapsulated fluorescent molecules and photothermal materials is proposed for potential applications in tumor diagnosis and treatment. As shown in Fig. 1(a), the hypoxia-sensitive fluorescent probes and black phosphorus/gold nanostars (BP/AuNS) hydrogels are immobilized on the fiber tip to implement a dual-purpose strategy, enabling the detection of the tumor hypoxia microenvironment and the enabling execution of PTT. The nitroreductase (NTR) fluorescence on the fiber surface enables precise sensing of the tumor microenvironment without any interference from the BP. The fluorescence intensity of the sensor can be further enhanced by introducing gold nanostars (AuNS). In addition to significant fluorescence enhancement, the AuNS improved the photothermal conversion of the black phosphorus. As the preferred photothermal tool, BP/AuNS stands out among various photothermal materials by delivering higher thermal energy and a broader thermal radiation range with low pump power, thereby enabling more efficient, safe, and controllable PTT. Moreover, to demonstrate the general applicability of our technique in cancer diagnosis and treatment, we performed sensing and photothermal tests using in vitro porcine liver tissue as a tumor model. This fiber medical technology provides a novel platform for cancer sensing and treatment [Fig. 1(b)], showing great promise for cancer clinical medicine.

Graphene (Gr), carbon nanotubes (CNTs), graphene oxide (GrO), MXene, AgNO3, ascorbic acid, HAuCl4, and low-melting agarose were purchased from Shanghai Macklin Biochemical Co., Ltd. The BP was purchased from Beijing Kehua New Materials Technology Co., Ltd. Gold seeds were purchased from Najing Technology Co., Ltd. HCl was purchased from Guangzhou Rongman Biotechnology Co., Ltd. HF was purchased from Guangzhou Chemical Reagent Factory. NTR fluorescent probes were prepared by our laboratory as previously reported^[22].

First, we etched the fiber tip with HF, and the fiber showed cone-column structure (100–400 µm). This approach is beneficial for the transmission of excitation light and the collection of fluorescence signals. To integrate NTR probes onto the fiber tip surface, a sequential process involving hydroxylation, silanization, and immobilization was carried out as previously described^[22]. Furthermore, AuNS were prepared using a seed-mediated approach, as detailed in previous research^[21]. We rapidly and sequentially poured HAuCl4, gold seeds, AgNO3, and ascorbic acid into dilute HCl and then reacted the resulting solution with thorough stirring to obtain AuNS. Nanomaterial hydrogels were prepared by adding photothermal nanomaterials and AuNS to liquid-phase agarose. Finally, we wrapped the hydrogel around the fiber surface and dried it to obtain nanomaterial hydrogel-based fibers.

The morphology of the samples was examined using a scanning electron microscope (SEM) (Apreo 2 SEM) and a transmission electron microscope (TEM) (TF20). We used a fiber fluorescence spectrometer (QE Pro, Ocean Optic) for NTR fluorescence data collection, Fourier transform infrared spectroscopy (Nicolet iS 10, Thermo) to characterize light absorption, a thermal imager (FOTRIC 225 s, FOTRIC) for IR imaging data collection during photothermal manipulation, and a commercial smartphone (HUAWEI Mate 20 Pro, Huawei) for dual-wavelength emission imaging data collection.

To test and calibrate the fiber fluorescence, mixtures of different NTR concentrations in PBS-NTR-fluorescent molecules were prepared. The fluorescent signals were recorded three times at 37°C to generate error lines. In addition, after subtracting the baseline (PBS spectrum) and normalizing the spectrum values, the data were fitted using calibration functions. The limit of detection (LOD) and limit of quantification (LOQ) were calculated using the following equations:$$\begin{gathered} XLOD=f−1(yblank¯+10/3×σ), \\ XLOQ=f−1(yblank¯+10×σ), \end{gathered}$$where (f) is the calibrating function, and (yblank¯±σ) is the blank sample data.

We simulated the heating area of the BP/AuNS hydrogel fibers using COMSOL. Considering that fiber PTT is influenced only by the photothermal effect of BP/AuNS, this simulation was set up for BP/AuNS fibers. When the 980 nm pump laser is applied, the laser travels through the optical fiber and interacts with the BP/AuNS, triggering the photothermal effect. Most of the laser energy is converted into heat at the fiber surface, which rapidly diffuses outward from the outer diameter of the fiber. The heat is conducted through thermal conduction and little body fluid convection, causing the surrounding tumor model to heat up.

The heat source model of the PTT fiber can be expressed as^[22]q(r)={0(r<r1)η·α·P(r,z)(r1<r≤r2),where η is the thermal conversion efficiency, r1 is fiber radius, r2 is the radius of the BP/AuNS hydrogel on the fiber surface, α is the laser absorption coefficient, and P(r,z) is the spatial distribution of the laser, which can be expressed as P(r,z)=P0·Pt·exp(−α·z),where P0 is the input power, and Pt(r) is the normalized energy distribution of the fundamental core mode.

The model can be regarded as two-dimensional and axisymmetric, with the core region generating the maximum amount of heat radially. The BP serves as the primary photothermal agent, while the AuNS is used in trace amounts. We use a finite element analysis model to simulate the temperature distribution of fiber PTT. The simulation results are consistent with the in vitro tissue photothermal tests. The remaining relevant parameters are as follows^[26]: kglass=1.4Wm−1K−1, Cpglass=730Jkg−1K−1, ρglass=2210kgm−3, kBP=20Wm−1K−1, CpBP=700Jkg−1K−1, ρBP=2690kgm−3, ktumor=0.52Wm−1K−1, Cptumor=3540Jkg−1K−1, and ρtumor=1079kgm−3, where ρ is the material density, Cp is the specific heat capacity at atmospheric pressure, and k is the thermal conductivity. The model uses the tumor boundary as the outer limit, with the probe performing PTT in the central region. The initial temperature was 308.15 K (35°C).

The immobilization of nanomaterials on an optical fiber surface can be an effective method for providing functionality to the fiber. Phase-change hydrogels were prepared to anchor various nanomaterials onto the fibers, excluding the possibility that different nanomaterials can combine differently with fibers. To enable effective tumor detection and treatment with optical fibers, we screened nanomaterials carried on fibers in terms of both the fluorescence detection of NTR (cancer marker) and the efficiency of photothermal conversion.

For fiber thermotherapy, we prioritize the temperature elevation of the fiber probe. Carbon nanotubes (CNTs), MXenes, graphene oxide (GrO), graphene (Gr), and BP were preferred for optical fiber photothermal testing due to their excellent photothermal effects. Therefore, we first tested and compared the temperatures provided by these photothermal materials on the fibers. As shown in Fig. 2(a), as the input 980 nm near-infrared region (NIR) power increases, the temperatures of the fiber probes with nanomaterials increase. The BP-decorated fiber (BP fiber) probes showed optimum photothermal properties, reaching a temperature of 212°C with only 150 mW of pump power in air. This approach avoided the risks of using high-power lasers. Moreover, the absorption spectra showed that the BP had broad-spectrum absorption and significantly higher absorption in the NIR compared to other nanomaterials [Fig. 2(b)]. The results demonstrated that the BP fiber was the optimal thermal probe and had the potential for rapid photothermal conversion in tumor therapy.

In addition, a previously reported oxygen-depleted fluorescent probe was utilized for NTR-specific detection via fluorescence. However, the presence of some photothermal conversion materials still causes sensing signal annihilation. Therefore, gold nanoparticles were incorporated to reduce the fluorescence quenching caused by the graphitic structure of certain nanomaterials and to enhance the fluorescence detection efficiency. We chose to utilize AuNS to enhance the fluorescence sensing functionality due to its enhanced local electromagnetic field and adjustable morphology, which enables further optimization of sensing performance. In Fig. 2(c), carbon nanotube/Au nanostars (CNTs/AuNS), MXene/Au nanostars (MXene/AuNS), graphene oxide/Au nanostars (GrO/AuNS), graphene/Au nanostars (Gr/AuNS), and black phosphorus/Au nanostars (BP/AuNS) were prepared separately on fibers for NTR fluorescence sensing. Compared to other fibers, the BP/AuNS fiber showed the highest fluorescence intensity, proving its ability to detect fluorescence. Thus, the combination of BP and AuNS is an excellent strategy for fluorescence sensing and photothermal conversion.

As shown in Fig. 2(d), we formulated hydrogels with a mixture of BP and AuNS (a gold nanostructure), which were covered with fibers and then allowed to dry naturally. The 10-µm-thick gel material was stably bound to the cone-column fiber (100–400 µm). The obtained fiber can be directly used for photothermal and fluorescence testing and has good robustness. In addition, the insets show the SEM images of the BP and TEM images of the AuNS with average diameters of 30 µm and 120 nm, respectively. The proposed hydrogel technique helped protect the encapsulated BP/AuNS, preventing it from being oxidized or degraded under environmental influences, thus safeguarding the probe and stabilizing its performance.

The fluorescence and photothermal properties of fibers are mainly related to the interaction between the nanomaterial and the light from the fiber. Then, we further improved the fluorescence sensing and photothermal conversion efficiency by regulating the AuNS structure, changing the content of the BP and the AuNS, and tailoring the fiber end diameter.

For fiber photothermal activity, as the amount of BP modification increases, indicated by the density of the BP/AuNS hydrogel on the surface, the fiber can achieve higher temperatures with the same pump power. As shown in Fig. 3(a), compared with that of the hydrogel with a lower BP density, the temperature of the fiber with a BP concentration of 5mgmL−1 reaches 305°C (300 mW), indicating a significant temperature increase. However, further increasing the BP density to 10mgmL−1 did not further enhance the photoheating outcome due to the capacity limit of the fiber surface area, but it did affect the fluorescence intensity for NTR sensing [Fig. 3(b)].

To solve the above issue, we introduced gold nanoparticles and customized gold nanostructures to enhance fluorescence sensing. The bare fiber, the BP/Au nanoparticle (BP/AuNP) fiber, the BP/AuNS(S30) fiber, the BP/AuNS(S20) fiber, and the BP/AuNS(S10) fiber were prepared^[21]. As shown in Figs. 3(c) and 3(d), due to the electromagnetic enhancement effect of the AuNS, the BP/AuNS(S10) fiber enables a 2.5-fold increase in fluorescence intensity compared to the bare silica fiber. This result indicated that the AuNS(S10) was the optimal gold nanostructure for fluorescence enhancement. Notably, increasing the concentration of the AuNS can also enhance the fluorescence signal, with a saturation concentration of 0.1 nM, as shown in Fig. 3(e). This was attributed to the limited space on the fiber surface for anchoring the AuNS. In addition, the AuNS can further enhance the fiber photothermal conversion efficiency due to the gold plasma effect. Figure 3(f) shows the temperature changes in the air for different fiber probes under laser pumping.

In addition, it is important to design a fiber structure for fluorescence sensing and photothermal effects. The end diameter of the fiber probe can directly influence the light–matter interaction of the NTR probes and the photosensitizers on the fiber, thereby providing different intensities of the evanescent field. As the fiber diameter decreases, the fluorescence signal intensity increases, as shown in Fig. 3(g). However, the fluorescence efficiency reaches saturation when the diameter is reduced to less than 100 µm because the evanescent field has already utilized diameters less than 100 µm. Moreover, when the fiber end diameter is 100 µm, the fiber probe has an LOD of 1.61ngmL−1 and a temperature of 255°C with a 200 mW pump [Figs. 3(h) and 3(i)]. There would be a compromise between the fiber evanescent field intensity and the density of the BP/AuNS concerning the fiber diameter, as shown in the parabolic-like curves. Therefore, the 150 µm end diameter fiber was preferred as the optimal probe for realizing integrated theranostics.

To validate the feasibility of the fiber theranostic strategy for clinical applications, BP/AuNS fibers were characterized for fluorescence sensing in a mixed PBS-NTR-NTR probe solution. As shown in Fig. 4(a), we performed in vitro calibration by testing the PBS-NTR-NTR probe mixtures with different NTR concentrations using a fiber-optic probe. The intensity of the emitted fluorescence peaks enhanced with increasing concentrations of NTR. Within a wide range of NTR concentrations (0–1000ngmL−1), the intensities of the emission peaks can be depicted by logistic fitting (R2=0.990). At lower concentrations (ranging from 0–30ngmL−1), an approximately linear correlation was observed (I=0.00576×C+0.20242; R2=0.998; I, intensity; C, concentration of NTR), with an LOD of 1.61ngmL−1 and an LOQ of 5.36ngmL−1. This demonstrated that cancer diagnosis can be effectively performed by BP/AuNS fibers. Furthermore, the fiber probe has high-temperature resistance, as shown in Fig. 4(c). After 1 min of high-temperature processing at 200°C, the fluorescence retention of the BP/AuNS fibers was 88.7%. However, the fluorescence sensing ability decreased after 7 days of fiber storage in air, resulting in a fluorescence retention of 71.6% [Fig. 4(b)]. This result indicated that the heat resistance of the BP/AuNS and NTR probes can retain their fluorescence sensing properties, but the BP/AuNS hydrogel slowly denatures in the air, leading to a decrease in the fluorescence detection efficiency of the sensor. In addition, higher temperatures, high humidity, and extreme pH conditions can also cause severe and irreversible effects on the probe.

Next, we characterized the theranostic functions of the BP/AuNS fiber sensor using ex vivo pork tissue as the experimental substrate. NTR fluorescence sensing and photothermal conversion were effectively validated via simulations and tests with a tumor model. As shown in Fig. 5(a), the PBS-NTR-NTR probe mixture is injected into fresh pork liver tissue, which is recognized as a biological model with a tumor microenvironment. With a plug-and-play strategy, the fiber optic can directly invade tissue for further diagnosis and treatment.

For fluorescence sensing, the sensor can differentiate tumor models with different NTR concentrations (0–1000ngmL−1), as shown in Fig. 5(b). We utilized a theranostic probe to detect the fluorescence intensity of the tumor model. Similar to the results of mixed-solution fluorescence testing, the spectrum indicated that the NTR density was directly proportional to fluorescence intensity. The statistical analysis was conducted on tumor models and blank samples. Compared to the blank sample, both the 10 and 50ngmL−1 samples yielded significantly positive results, demonstrating that fiber probes can effectively measure the NTR in tumor tissues.

To evaluate the therapeutic effectiveness of the BP/AuNS fibers, we also characterized the range of photothermal action. As shown in Figs. 5(c) and 5(d), we simulate BP/AuNS fiber-mediated thermally driven processes by COMSOL. The simulation results indicate that thermal energy in the air and tumor accumulates with increased heating time. The thermal levels are visually represented in the simulation diagram, highlighting the temperature differences in various regions. According to previous reports^[27,28], irreversible damage to tumor tissue occurs when hyperthermia temperature exceeds 42°C, and 10 min of high temperatures (42°C–46°C) can lead to necrosis of tumor cells. Therefore, we considered the 45°C isotherm to be the effective PTT boundary for tumor necrosis. As shown in Fig. 5(c), the radiation radius of the photothermal agent of the fiber in air reached a maximum of 4.35 mm (45°C) in 1 min. For the tumor model in Fig. 5(d), the simulation diagram shows that after 1 min of fiber-mediated PTT, the necrotic tissue region has a radius of 1.30 mm. When the PTT duration is increased to 15 min, the radius of the necrotic tissue region expands to 2.50 mm. Then, we characterized the thermal radiation range of the BP/AuNS fibers using a photothermal imager to verify the PTT effectiveness and action intervals in ex vivo pork liver. As shown in Fig. 5(e), the thermal radiation range of the fiber expands with increasing NIR laser power. When the power increased from 0 to 200 mW, the 45°C isotherm expanded from 0 to 2.65 mm, and the average tissue temperature increased from 23.9°C to 52.2°C. After 10 min of 150 mW photothermal radiation, the photothermal resistance tended to be optimal, as shown in Fig. 5(f), where the thermal radiation range (45°C) and average temperature were 2.4 mm and 46.4°C, respectively. The results of the simulations and tests were generally consistent. Theoretically, tumors can be effectively eradicated and suppressed at this temperature. Thus, these results demonstrated the promising application of BP/AuNS fibers as an ideal diagnostic and therapeutic tool for cancer. However, our fiber probe is not suitable for reuse in practical applications. On the one hand, due to the sensitivity of the BP, repeated use may lead to performance degradation caused by exposure to environmental factors such as oxygen and moisture, which can severely affect the probe’s photothermal and sensing performance. On the other hand, the hypoxia fluorescence molecules we utilized react with tumor markers, resulting in a reduction of sensing performance after each use. Fortunately, the fiber can be reused after cleaning, and simple functionalization can ensure reproducibility and stability of the device.

In summary, BP has been innovatively applied in fiber sensing and photothermal optimization. It offers a design pathway that does not interfere with fluorescence signals while enabling more efficient and safe PTT. Based on this, we proposed a nanomaterial-incorporated hydrogel fiber sensor that operates in a plug-and-play manner and that is used for minimally invasive photomedicine. We achieved NTR detection and excellent fiber photothermal effects using fluorescent molecules and BP/AuNS hydrogels on the same fiber. The fiber fluorescence intensity increased as the concentration of the NTR increased, and the LOD and LOQ were 1.61 and 5.36ngmL−1, respectively. BP/AuNS fibers can be used to accurately diagnose in vivo tumors by assessing NTR levels. In addition, the BP/AuNS hydrogel on the fiber can release thermal energy via the low-power 980 nm laser. The evaluation of tumor simulations and models showed that the effective fiber PTT range radius was ∼2.5mmin vivo. The fabricated BP/AuNS fiber was also applied to demonstrate an interventional photomedicine in a tumor model, which was proposed here for cancer theranostics. Furthermore, the application of hydrogels enables the combination of optical fibers and drugs, promoting the integration of fiber medicine and chemotherapy. However, the strategy has obvious drawbacks. Although the protection provided by the hydrogel reduces the oxidation and degradation of black phosphorus, the probe struggles to withstand long-term exposure to high temperatures, high humidity, and extreme pH environments. This, along with the consumption of fluorescent molecules on the probe, indicates that the fiber probe is not suitable for repeated use. Once technological advancements address these issues, with remarkable detection sensitivity, good photothermal effects, and unique minimally invasive intervention strategies, BP/AuNS fibers are promising for broad application in the field of oncology photomedicine.