Organic Semiconducting Photoacoustic Nanodroplets for Laser-Activatable Ultrasound Imaging and Combinational Cancer Therapy

Abstract

Combination of photoacoustic (PA) and ultrasound (US) imaging offers high spatial resolution images with deep tissue penetration, which shows great potential in applications in medical imaging. Development of PA/US dual-contrast agents with high contrast and excellent biocompatibility is of great interest. Herein, an organic semiconducting photoacoustic nanodroplet, PS-PDI-PAnD, is developed by stabilizing low-boiling-point perfluorocarbon (PFC) droplet with a photoabsorber and photoacoustic agent of perylene diimide (PDI) molecules and coencapsulating the droplet with photosensitizers of ZnFPc molecules. Upon irradiation, the PDI acts as an efficient photoabsorber to trigger the liquid-to-gas phase transition of the PFC, resulting in dual-modal PA/US imaging contrast as well as photothermal heating. On the other hand, PFC can serve as an O reservoir to overcome the hypoxia-associated resistance in cancer therapies, especially in photodynamic therapy. The encapsulated photosensitizers will benefit from the sustained oxygen release from the PFC, leading to promoted photodynamic efficacy regardless of pre-existing hypoxia in the tumors. When intravenously injected into tumor-bearing mice, the PS-PDI-PAnDs show a high tumor accumulation via EPR effect. With a single 671 nm laser irradiation, the PS-PDI-PAnDs exhibit a dual-modal PA/US imaging-guided synergistic photothermal and oxygen self-enriched photodynamic treatment, resulting in complete tumor eradication and minimal side effects. The PS-PDI-PAnDs represents a type of PFC nanodroplets for synergistic PDT/PTT treatment upon a single laser irradiation, which is expected to hold great potential in the clinical translation in dual-modal PA/US imaging-guided combinational cancer therapy.

Photoacoustic Imaging: Contrast Agents and Their Biomedical Applications

“…Organic molecular PA contrast agents, including porphyrin, melanin, cyanine‐based dyes, and perylene‐diimide (PDI), have been widely applied in PA imaging due to their excellent biodegradability and biocompatibility. In 2011, Zheng and co‐workers developed porphysomes by combining porphyrin with phospholipids and integrating porphyrin–phospholipids into nanovesicles via a self‐assembly approach .…”

“…Copyright 2017, American Chemical Society. (I–K) Reproduced with permission . Copyright 2018, American Chemical Society.…”

“…PDI (Figure G), as a widely used semiconducting polymer, has received considerable attention in PA imaging due to its strong NIR‐light‐absorption ability and excellent biocompatibility. Moreover, PDI possesses very high photothermal stability and photothermal conversion efficiency, and is easily modified . Cheng and co‐workers successfully developed an excellent contrast agent of PDI‐based NIR‐absorptive organic NPs for PA imaging in the tumor region of the tumor‐bearing mice .…”

“…Fan and co‐workers rationally designed an efficient PA contrast agent consisting of amphiphilic PDI derivatives and cRGD‐modified NIR‐absorptive organic semiconducting NPs through a self‐assembly method, which could be used to selectively light up early thrombus in living mice (Figure H). Recently, Cheng and co‐workers developed photosensitizer (PS)‐loaded PDI PA activating nanodroplets (PS‐PDI‐PAnD) consisting of a PDI shell with long alky chains and a liquid perfluoropentane core . The photosensitizer ZnF16Pc showed excellent compatibility at the interlayer of the core–shell nanostructure (Figure I,J).…”

Advanced Nanotechnology Leading the Way to Multimodal Imaging‐Guided Precision Surgical Therapy

“…[149][150][151] Biocompatible SPNs were developed with biodegradability, being advantageous compared with inorganic probes. [149][150][151] Biocompatible SPNs were developed with biodegradability, being advantageous compared with inorganic probes.…”