image: a, the fiber-optic therapeutic probe features the minimal invasive nature to target the tumor in vivo. The fiber probe has photothermal therapy, drug delivery and thermally controlled release, temperature and drug release monitoring which can realize synergistic therapy as the pieces of puzzle displayed on the diagram. b, The schematic diagram drug release of optic-fiber therapeutic probe with a Dox@Agarose film. The low-melting agarose carrying Dox are coated on fiber surface, which can be well-reserved under the melting threshold. In the operation, Dox will be precisely released from the agarose film at the tumor lesion as the localized temperature was increased by transmitting the 980 nm pump laser into the fiber probe. c, Principle of the in-situ sensing of the fiber probe. The peak signal of FBG moving to longer wavelength indicates the increasing temperature, and interference signal of MZI shifting to shorter wavelength demonstrated the successful release of drugs. Abbreviations: MZI: Mach–Zehnder interferometer; FBG: Optical fiber Bragg grating; Δλ: wavelength shift.
Credit: by Yongkang Zhang et al.
Cancer, caused by the pathophysiological alterations in cell division, is one of the most fatal diseases worldwide. However, the poor delivery efficiency (only 1% of total dose of administration can arrive at tumor), systemic toxicity (the substantial amount of dissociative drugs would inevitably damage the normal tissues and organs mediated by circulatory system), and the lack of pharmacokinetic monitoring are the critical limitations of current chemotherapy. photoheating mediated activation of drug is a promising scheme to elicit on-target releasing thanks to the excellent spatiotemporal controllability and non-invasiveness of laser radiation. Nevertheless, the limited tissue penetration of external light radiation, time-consuming and insufficiency of drug retention, and lack of in-situ drug release monitoring during the treatment discourages the current photothermal-chemotherapy technology.
In a new paper published in Light: Science & Application, a team of scientists, led by Professor Bai-Ou Guan from Guangdong Provincial Key Laboratory of Optical Fiber Sensing and Communications, Institute of Photonics Technology, Jinan University, China, and co-workers have developed a fiber-optic drug delivery strategy for synergistic cancer photothermal-chemotherapy. Besides shipping photons to deep tumor lesions, the optical fiber can load photothermo-sensitizers and chemotherapeutics, and precisely guide them targeting to tumor via interventional method. As is depicted in Figure 1(b), once entering tumor, the fiber probe can be rapidly fueled by the incidence of laser to generate local hyperthermia, in which the fiber core dopants, i.e., the rare-earth ions, perform as photothermo-sensitizers. The localized high temperature then activates the low-melting-point agarose film, which is glued on fiber, to release the originally encapsulated doxorubicin (Dox).
The abundant degree-of-freedom of optical fiber allows the layout of multiple integrated sensors, such as Mach–Zehnder interferometer (MZI) based on the reflective multimode-singlemode fiber splicing structure and fiber Bragg grating (FBG), to quantify the release of antitumor drugs and govern the temperature of lesion by transmitting data to clinicians in the operating room and even in remote area, as is illustrated in Figure 1(c).
Compared with the conventional external laser radiation-based drug release method, fiber optic drug delivery not only overcomes the penetration limit for tackling deep and large tumors but also enhances the permeability and retention of Dox to scavenge the whole tumor based on the newly explored “central-to-peripheral” permeation mechanism, turning neoplasms into sitting ducks and regulating the time. Specifically, minimal invasive fiber-optic photothermal therapy can enhance the vascular permeability of tumor and regulates the TME, rendering the drugs fully pervading throughout the tumor. Furthermore, the melted agarose hydrogel particles that wrap drugs can dock at the tumor with a longer period and continue to make use of Dox to destroy tumor cells, which share similar effect with transcatheter arterial chemoembolization (TACE) but with a more preferable drug releasing rate. Either in vitro and in vivo experimental results confirm the pronounced efficacy of the fiber-optic drug delivery probe.
About the biosafety, the employment of agarose materials and Dox, which were both approved by Food and Drug Administration (FDA), and the photothermo-sensitizers, which are caged in the fiber core and taken out with the fiber after treatment, adequately guarantee the bio-safety of this new approach. The results of drug biodistribution after treatment further discloses high tumor-targeted efficiency of the proposed drug delivery strategy, with no evidence of affecting normal tissues and organs.
This technique lifts beyond a therapeutic probe by providing a high-efficiency and compatible drug screening and evaluation strategy for the research and development of new anticancer drugs, and even the re-assessment of the drugs that had been ruled-out due to the systemic toxicity.
Journal
Light Science & Applications
Article Title
Fiber-optic drug delivery strategy for synergistic cancer photothermal-chemotherapy