NIR-Responsive Microbubble Delivery Platforms for Controlled Drug Release in Cancer Therapy

Abstract

Cancer remains one of the leading causes of death worldwide. Therefore, the continuous development of effective therapeutic strategies is necessary. Conventional anticancer chemotherapy has low bioavailability and poor systemic distribution, resulting in serious side effects and limited therapeutic efficacy. To address these limitations, drug delivery systems that respond to external stimuli have been developed to release drugs at specific sites. In this study, a phase transition-based bubble-mediated emulsion system was developed to enable near-infrared (NIR)-induced drug release. This system consists of an oil phase, 2H,3H-perfluoropentane (PFC), a fluorinated liquid gas that evaporates at a certain temperature, and encapsulated IR-780 and paclitaxel to maintain stable microbubbles. Under NIR irradiation, IR-780 exhibits a photothermal conversion effect, which increases the temperature. Above the critical temperature, PFC undergoes a phase transition into gas, forming gas bubbles. This phase transition leads to a rapid volume expansion, destroys the microbubble structure, and triggers drug release. The NIR-responsive microbubble system developed in this study facilitated targeted and selective drug release through precise temperature control using the photothermal effects and phase transition. This system provides a novel platform to improve the efficacy of cancer therapies.

Keywords: cancer therapy; controlled release; drug delivery system; microbubble.

Scheme 1

Illustration of the NPMB system enabling controlled drug release for targeted cancer therapy.

Figure 1

(a) Optical microscopy image of NPMBs. (b) Size distribution analysis of free MBs, IR-780-loaded MBs, PTX-loaded MBs, and NPMBs measured by DLS. (c) CLSM images of NPMBs showing green fluorescence from IR-780 and red fluorescence from the model drug.

Figure 2

(a) Optical microscopy images showing morphological changes of NPMBs at various temperatures (20 °C, 40 °C, 60 °C, and 80 °C). (b) Temperature changes of NPMBs under different NIR irradiation intensities (0.5, 0.7, 1.0, 1.2, and 1.8 W/cm²). (c) Thermal response of NPMBs during repeated On–Off cycles of NIR irradiation. (d) Thermal imaging results comparing PBS solution, free IR-780, and NPMBs under NIR irradiation.

Figure 3

(a) Cumulative PTX release from NPMBs under different NIR irradiation intensities. (b) Time-dependent PTX release from NPMBs at 1.8 W/cm².

Figure 4

(a) Cell viability of HeLa cells treated with NPMBs under NIR irradiation. (b) Live/Dead cell staining images of HeLa cells under different treatment conditions: Control (untreated), NIR irradiation only, free IR-780, free PTX, NPMB without NIR irradiation, and NPMB with NIR irradiation. Green fluorescence (live cells, FDA staining) and red fluorescence (dead cells, PI staining).