The development of multifunctional nanoparticles has attracted increasing attention. The versatility of nanoparticles largely depends on their physiochemical properties (especially size). However, the optimized size range may be different for the bioapplications of each function associated with multifunctional nanoparticles. It is important to investigate every optimized size range to ascertain which size enables the best function of the nanoparticles before deciding their final size. In this work, we synthesized a series of monodisperse Fe3O4 nanoparticles with identical surface properties ranging in size from 60 to 310 nm and systematically investigated their biobehavior and application. Our data indicate that compared to their large counterparts, small Fe3O4 nanoparticles exhibited greater cellular internalization and deeper penetration into multicellular spheroids, thus enabling a higher photothermal ablation efficacy in vitro. Interestingly, larger Fe3O4 nanoparticles showed greater accumulation in tumors, thereby inducing more efficient tumor growth inhibition. In addition, 120 nm may be the optimal diameter of Fe3O4 nanoparticles for magnetic resonance imaging and photoacoustic tomography in vitro. However, more efficient in vivo imaging mediated by Fe3O4 nanoparticles will predominantly depend on their high accumulation. Our work presents a different appropriate size range for each biofunction of Fe3O4 nanoparticles, which could be a valuable reference for future nanoparticle design.
Both photothermal therapy (PTT) and photodynamic therapy (PDT) are phototherapeutic approaches, which have been widely investigated for cancer therapy mediated by an external light source. Here, a nanosystem presenting the synchronous PTT and PDT effect realized through one-step near-infrared (NIR) light irradiation is reported. This system was fabricated by conjugating indocyanine green (ICG) on hollow gold nanospheres (HAuNS) using branched-polyethylenimine (PEI, MW = 10 kDa) as optimal linker, which provided a high ICG payload as well as a covering layer with suitable thickness on HAuNS to maintain ICG fluorescence and reactive oxygen species (ROS) productivity. The resulting system (ICG-PEI-HAuNS) had the molar ratio of ICG:PEI:Au = 3:0.33:5. Compared with free ICG, ICG-PEI-HAuNS exhibited dramatically enhanced stability of ICG molecules and greater intratumoral accumulation. The conjugation of ICG caused significantly higher plasmon absorption of ICG-PEI-HAuNS in the NIR region compared with HAuNS alone, inducing remarkably enhanced photothermal conversion efficiency and synchronous photodynamic effect under NIR light irradiation. Interestingly, compared with PTT or PDT alone, synchronous PTT and PDT produced by ICG-PEI-HAuNS upon NIR light irradiation induced significantly stronger antitumor and metastasis inhibition effects both in vitro and in vivo, which might be a promising strategy for cancer treatment.
Purpose To develop a near-infrared (NIR) light-sensitive liposome, which contains hollow gold nanospheres (HAuNS) and doxorubicin (DOX), and evaluate their potential utility for enhancing antitumor activity and controlling drug release. Methods The liposomes (DOX&HAuNS-TSL) were designed based on a thermal sensitive liposome (TSL) formulation, and hydrophobically modified HAuNS were attached onto the membrane of the liposomes. The behavior of DOX release from the liposomes was investigated by the dialysis, diffusion in agarose gel and cellular uptake of the drug. The biodistribution of DOX&HAuNS-TSL was assessed by i.v. injection in tumor-bearing nude mice. Antitumor efficacy was evaluated both histologically using excised tissue and intuitively by measuring the tumor size and weight. Results Rapid and repetitive DOX release from the liposomes (DOX&HAuNS-TSL), could be readily achieved upon NIR laser irradiation. The treatment of tumor cells with DOX&HAuNS-TSL followed by NIR laser irradiation showed significantly greater cytotoxicity than the treatment with DOX&HAuNS-TSL alone, DOX-TSL alone (chemotherapy alone) and HAuNS-TSL plus NIR laser irradiation (Photothermal ablation, PTA, alone). In vivo antitumor study indicated that the combination of simultaneous photothermal and chemotherapeutic effect mediated by DOX&HAuNS-TSL plus NIR laser presented a significantly higher antitumor efficacy than the PTA alone mediated by HAuNS-TSL plus NIR laser irradiation. Conclusions Our study could be as the valuable reference and direction for the clinical application of PTA in tumor therapy.
The development of multifunctional nanoplatforms based on magnetic nanoparticles (MNPs) has attracted increasing attention. MNPs especially exhibit excellent responsiveness under the guidance of an external magnetic field (MF), resulting in tumor-specific, targeted delivery. The behavior and magnetic-targeting efficiency of MNPs largely depend on their physiochemical properties, especially the particle size; however, the optimal size range may vary across the multiple bioapplications associated with multifunctional nanoparticles. The optimal size range of nanoparticles for external MF-mediated targeted delivery has rarely been reported. In this work, we synthesized a series of monodisperse FeO nanoparticles with identical surface properties ranging in size from 10 to 310 nm, and we systematically investigated their behavior and MF-assisted antitumor efficacy. Our data indicated that smaller FeO nanoparticles exhibited greater cellular internalization, while larger FeO nanoparticles showed greater tumor accumulation. Larger FeO nanoparticles exhibited stronger magnetic responsiveness both in vitro and in vivo, which could be used to further induce increased accumulation of nanoparticles and their payload (e.g., doxorubicin) into the tumor site under the guidance of an external MF. Our work demonstrated that larger FeO nanoparticles, with a diameter of up to 310 nm, exhibited the best magnetic-targeting efficiency mediated by an external MF and the strongest antitumor efficacy from combination photothermal-chemotherapy. Our results could serve as a valuable reference for the future design of MNPs and their targeted delivery via the modulation of an external MF.
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