Photoinduced cancer therapy, a light-based therapeutic intervention, has attracted vast attention of numerous researchers due to the eminent characteristics, such as non-invasiveness, minimized side effects, spatiotemporal control and biological adaptability [1], [2], [3], [4], [5]. Photothermal therapy (PTT) and photodynamic therapy (PDT) are the main forms of photoinduced cancer therapy. Upon light irradiation, photosensitizers can be activated to generate heat for PTT [6] or singlet oxygen (1O2) for PDT [7], leading to cancer cell death and antitumor immunity. Conventional photosensitizers are mainly anthraquinones, porphyrins and chlorins with relatively short-wavelength absorption, limiting the anticancer applications because of the worse light penetration [8], [9]. Recently, near-infrared (NIR) activated photosensitizers (700–900 nm) are highly desired for photoinduced cancer therapy with less photodamage and deeper penetration, which can be absorbed minimally in tissues [10], [11]. It should not be overlooked that existing NIR activated photosensitizers also suffer from other defects, including poor photostability, low 1O2/heat generation capabilities, and ordinary antitumor immunity [12], [13], [14], [15], [16].
Synergistic implementation of PDT and PTT using optimized NIR-absorbing photosensitizers is expected to accomplish precision cancer treatment in an efficient, specific and controlled manner [17], [18], [19]. Very recently, boron dipyrromethene (BODIPY)-based cancer theranostics can employ multimodal imaging and therapies, which has garnered wide interest in the field of medicine, chemistry and biology [20]. BODIPY dyes have advantages in three main aspects, including intense absorption in the NIR range [21], [22] and tunable phototherapy (PDT and PTT) performance by rational molecular design [23], [24], [25], and excellent photophysical/photochemical properties [26]. Importantly, BODIPY-based photosensitizers can not only separately trigger PDT and PTT processes [27], [28], [29], [30], but also can be used for cancer therapy by synergetic PDT and PTT [31], [32]. To overcome the limited biological application of BODIPY dyes due to the hydrophobicity, PEGylation and chemical modification can be used [33], [34]. The amphiphilic modification is beneficial to assemble BODIPY dyes into multifunctional nanoparticles in aqueous solution and expand applications in the field of anticancer [33], [34]. On the other hand, dyes with a donor–acceptor-donor (D-A-D) architecture are also widely developed for PDT and PTT, because the reduced energy gap can increase absorption and emission wavelengths to obtain satisfactory photometric characteristics and tissue permeability [35], [36], [37], [38]. Consequently, BODIPY-based amphiphilic D-A-D dyes have the potential to be assembled into nanoparticles and utilized to achieve NIR-triggered PDT and PTT.
In this work, we reported a novel BODIPY-based amphiphilic dye (BDP-AP) with enhanced D-A-D structure, which can self-assemble into stable nanoparticles (BDP-AP NPs) in aqueous solution for NIR-triggered PDT and PTT. Through conjugating N,N-dimethylaniline (electron donor) on BODIPY (electron acceptor), D-A-D architecture structure was constructed. Next, the amphiphilic modification of BODIPY was realized by using amide bond to connect hydrophilic moiety. The assembled BDP-AP NPs have uniform morphology (diameter: ∼189 nm), and the maximum absorption peak is in the NIR range (770 nm). Under our test conditions, BDP-AP NPs simultaneously generated 1O2 and achieved preeminent photothermal conversion efficiency (61.42 %). Though synergetic PDT and PTT, 40 μg/mL BDP-AP NPs dramatically killed both 4T1 breast cancer cells in vitro and 4T1 tumor in vivo, and the antitumor process has no obvious side-effects on other tissues or organs of 4T1 tumor-bearing BALB/c female mice. Our BDP-AP NPs have promising applications in cancer therapy and intervention, and are expected to facilitate the rapid development of the synergistic PDT and PTT field.
Comments (0)