The combination of optical fiber and phototheranostic agents has emerged as a promising strategy to address the challenges of limited light penetration depth and systemic toxicity of nanomaterials. However, the multiplexing potential of fiber-optic probes remains underrated, resulting in enlarged incisions, repeated invasive procedures, and a lack of real-time therapeutic feedback. Herein, we propose a scheme for single‑fiber multifunctional integration leveraging wavelength division multiplexing technology.
As a proof-of-concept, by co-immobilizing pH indicator, temperature indicator, and photothermal agent with non-overlapped excitation bands onto tapered optical fiber surface, a fiber-optic theranostic probe enabling closed-loop tumor photothermal therapy was developed. Pre-treatment, the probe can achieve tumor edge identification through revealing the tumor pH gradient. Intra-treatment, the photothermal agent can convert optical energy into heat for photothermal therapy, while simultaneous temperature monitoring enables precise thermal dose control. Post-treatment, rapid efficacy assessment can be achieved via real-time monitoring of the reversal of acidic tumor microenvironment.
Animal experiments validate the excellent therapeutic efficacy and biocompatibility of the probe. This research opens new avenues for multifunctional fiber-optic theranostic platforms, where modular wavelength assignment enables customizable minimally invasive interventions and feedback monitoring, holding significant promise for both clinical practice and mechanistic exploration.
Cancer has become one of the most significant global public health challenges. In 2022 only, approximately 20 million new cancer cases were diagnosed worldwide while nearly 10 million cancer-related deaths. Motivated by this scenario, substantial efforts have been directed toward developing diagnostic and therapeutic methods with enhanced accuracy and efficacy. Theranostics, which integrates diagnostic and therapeutic functions into one spatially colocalized platform, allows for immediate, targeted therapy after diagnosis and enables real-time monitoring of therapeutic dose and efficacy, paving the way for personalized precision medicine.
In the last decade, photo-theranostic has garnered widespread attention due to its advantages of excellent specificity, high spatiotemporal controllability, and non-ionizing nature. However, several critical challenges prevent its clinical translation. One major obstacle is the inherently limited penetration depth of light (typically less than 10 mm) due to the scattering and absorption by tissues. Although fluorescence dyes in the second near-infrared (NIR-II) window exhibited unprecedented penetration depth, their design and synthesis remain a great challenge. Another significant limitation arises from the systemic toxicity caused by non-specific accumulation of nanomaterials on normal tissues and organs.
Against this background, the combination of optical fiber and phototheranostic agents has emerged as a promising solution Flexible and compact optical fibers enable end-to-end light transmission with minimal loss, facilitating sensing and treatment of deep-seated tumors, including surgically inaccessible sites. Furthermore, immobilizing phototheranostic agents on or within optical fibers effectively mitigates off-target toxicity through localized confinement. Benefitting from these features, optical fibers have been successfully applied for minimally invasive tumor therapy and in vivo biomarker monitoring.
Despite recent advances, the multiplexing potential of fiber-optic probes remains underrated. Current research remains limited to single-function-per-fiber implementations or suffers from inter-functional crosstalk, which primarily arises from spectral overlap in the absorption or emission bands among the functional reagents used. Consequently, achieving multi-parameter monitoring or integrated theranostics demand multi-fiber configurations. This inevitably increases device rigidity and dimensions, decreasing compatibility for interventional techniques while elevating risks of tissue damage and post-treatment inflammation .
Inspired by the wavelength division multiplexing (WDM) technology that leverages wavelength separation to enhance the transmission capacity of a single optical fiber, which has been widely used in fiber-optic communication, we propose in this work a scheme for fiber-optic multifunctional integration through modular wavelength assignment of photo-indicators&sensitizers to fully utilize the wavelength reservoir while suppress inter-functional crosstalk: (1) the UV–visible bands are employed for fluorescence probe excitation and emission to match the spectral characteristics of conventional fluorophores; (2) the NIR band, within the biological transparency window, is employed for photosensitizer excitation, ensuring compatibility with existing clinical therapeutic lasers and photosensitizers.
Specifically, a pH indicator (HPTS-IP, derivative of 8-hydroxy-1,3,6-pyrene trisulfonic acid), a temperature indicator (LnMOF, lanthanide metal-organic framework material), and a photothermal agent (ICG, indocyanine) were co-encapsulated within a hydrogel matrix and immobilized onto tapered optical fiber surface. Crucially, the excitation bands of these agents do not overlap with each other.
Consequently, the function of this probe can be switched on demand by using different excitation wavelengths. Clinically, this compact probe (diameter = 440 μm) can access tumor lesions via interventional procedures, enabling closed-loop tumor photothermal therapy with real-time feedback. Pre-treatment, the probe can achieve tumor edge identification through revealing the tumor pH gradient. Intra-treatment, the photothermal agent converts optical energy into heat for photothermal therapy , while simultaneous temperature monitoring enables precise thermal dose control. Post-treatment, rapid efficacy assessment can be achieved via real-time monitoring of the reversal of acidic tumor microenvironment (TME). This research establishes a paradigm shift for multifunctional fiber-optic theranostic platforms, offering significant potential for advancing both clinical practice and tumor mechanism research.
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