A light-controllable specific drug delivery nanoplatform for targeted bimodal imaging-guided photothermal/chemo synergistic cancer therapy.

Breast cancer is a severe threat to the health and lives of women due to its difficult early diagnosis and the unsatisfactory therapeutic efficacy of breast cancer treatments. The development of theranostic strategies to combat breast cancer with high accuracy and effectiveness is therefore urgently needed. In this study, we describe a near-infrared (NIR) light-controllable, targeted and biocompatible drug delivery nanoplatform (PFH-PTX@PLGA/SPIO-Her) for photoacoustic (PA)/ultrasound (US) bimodal imaging-guided photothermal (PTT)/chemo synergistic cancer therapy of breast cancer. Carboxyl-modified PEGylated poly (lactic-co-glycolic acid) (PLGA-PEG-COOH) constituted the skeleton of the nanoplatform. Especially, the antibody Herceptin was modified onto the surface of nanoplatform for active HER2-targing to facilitate the tumor accumulation of the nanoplatform. The encapsulated superparamagnetic iron oxide (SPIO) nanoparticles could be employed as an excellent PA imaging agent to guide tumor therapy. When exposed to NIR light, the SPIO also could transform NIR light into thermal energy for photothermal ablation of tumor. The NIR-induced thermal effect subsequently triggered the optical droplet vaporization (ODV) of perfluorohexane (PFH) to generate PFH gas bubbles, which not only achieved the US imaging enhancement, but also contributed to the release of loaded paclitaxel (PTX) from the nanoplatform for significantly improving PTT therapeutic efficacy. Our results demonstrated that the targeted tumor accumulation, accurate real-time bimodal imaging, and the abundant drug release at the tumor site were all closely associated with the PTT therapeutic efficacy. Therefore, the theranostic nanoplatform is a very promising strategy for targeted imaging-guided photothermal/chemo synergistic tumor therapy with high therapeutic efficacy and minimized side effects. STATEMENT OF SIGNIFICANCE: Breast cancer is the most frequent cancer in women. Herein, we successfully developed a light-controllable and HER2 targeted theranostic nanoparticels (PFH-PTX@PLGA/SPIO-Her) as a specific drug delivery nanoplatform to overcome the low accuracy of tumor detection and the low specificity of traditional chemo-therapeutic protocols. The study demonstrated that PFH-PTX@PLGA/SPIO-Her could actively target to breast cancer cells with positive HER2 expression. The biocompatible PFH-PTX@PLGA/SPIO-Her nanoparticles as both photoacoustic/ultrasound bimodal imaging agents, photothermal-conversion nanomaterials (photothermal hyperthermia) and controllable drug delivery nanoagents (optical droplet vaporization) have completely eradicated the tumor without severe side effects. The theranostic strategy not only integrates strengthens of traditional imaging or therapeutic modalities, but also paves a new way for the efficient cancer treatment by taking the advantage of quickly-developing nanomedicine.

Guo Y ，Wang XY ，Chen YL ，Liu FQ ，Tan MX ，Ao M ，Yu JH ，Ran HT ，Wang ZX ... -  《-》

Folate-receptor-targeted laser-activable poly(lactide-co-glycolic acid) nanoparticles loaded with paclitaxel/indocyanine green for photoacoustic/ultrasound imaging and chemo/photothermal therapy.

Liu F ，Chen Y ，Li Y ，Guo Y ，Cao Y ，Li P ，Wang Z ，Gong Y ，Ran H ... -  《International Journal of Nanomedicine》

Targeted polydopamine nanoparticles enable photoacoustic imaging guided chemo-photothermal synergistic therapy of tumor.

Near infrared light responsive nanoparticles can transfer the absorbed NIR optical energy into heat, offering a desirable platform for photoacoustic (PA) imaging guided photothermal therapy (PTT) of tumor. However, a key issue in exploiting this platform is to achieve optimal combination of PA imaging and PTT therapy in single nanoparticle. Here, we demonstrate that the biodegradable polydopamine nanoparticles (PDAs) are excellent PA imaging agent and highly efficient for PTT therapy, thus enabling the optimal combination of PA imaging and PTT therapy in single nanoparticle. Upon modification with arginine-glycine-aspartic-cysteine acid (RGDC) peptide, PDA-RGDC can successfully target tumor site. Moreover, PDA-RGDC can load a chemotherapy drug, doxorubicin (DOX), whose release can be triggered by near-infrared (NIR) light and pH dual-stimuli. The in vitro and in vivo experiments show that this platform can deliver anti-cancer drugs to target cells, release them intracellular upon NIR irradiation, and effectively eliminate tumors through chemo-photothermal synergistic therapeutic effect. Our results offer a way to harness PDA-based theranostic agents to achieve PA imaging-guided cancer therapy. NIR-light adsorbed nanoparticles combing the advantage of PAI and PTT (TNP-PAI/PTT) are expected to play a significant role in the dawning era of personalized medicine. However, the reported Au-, Ag-, Cu-, Co-, and other metal based, carbon-based TNP-PAI/PTT suffer from complex multicomponent system and poor biocompatibility and biodegradability. To overcome this limitation, biocompatible polydopamine nanoparticles (PDAs), structurally similar to naturally occurring melanin, were designed as both PA imaging contrast agent and a chemo-thermotherapy therapy agent for tumor. RGDC peptide modified PDAs can improve the PA imaging and PTT efficiency and specific targeted deliver doxorubicin (DOX) to perinuclear region of tumor cells. Our finding may help the development of PDA-based nanoplatform for PA imaging-directed synergistic therapy of tumor in clinic.

Li Y ，Jiang C ，Zhang D ，Wang Y ，Ren X ，Ai K ，Chen X ，Lu L ... -  《-》

Chemotherapeutic drug-photothermal agent co-self-assembling nanoparticles for near-infrared fluorescence and photoacoustic dual-modal imaging-guided chemo-photothermal synergistic therapy.

Multimodal imaging-guided synergistic combination therapy has shown great potential for cancer treatment. However, the nanocarrier-based theranostic systems suffer from batch-to-batch variation, complexity of multicomponent, poor drug loading, and carrier-related toxicity issues. To address these issues, herein we developed a novel carrier-free theranostic system with nanoscale characteristics for near-infrared fluorescence (NIRF) and photoacoustic (PA) dual-modal imaging-guided synergistic chemo-photothermal therapy (PTT). Indocyanine green (ICG) and epirubicin (EPI) could co-self-assemble into small molecular nanoparticles (NPs) in aqueous solution without any molecular precursor or excipient via collaborative interactions (electrostatic, π-π stacking, and hydrophobic interactions). The exceptionally high dual-drug loading (∼92wt%) ICG-EPI NPs showed good physiological stability, preferable photothermal response, excellent NIRF/PA imaging properties, pH-/photo-responsive drug release behavior, and promoted cellular endocytosis compared with free ICG or EPI. Importantly, the ICG-EPI NPs showed excellent tumor targeting ability with high spatial resolution and deep penetration via in vivo NIRF/PA dual-modal imaging. Moreover, in comparison with individual chemotherapy or PTT, the combinational chemo-PTT therapy of ICG-EPI NPs with NIR laser irradiation synergistically induced apoptosis and death of cancer cells in vitro, and showed synergistic chemo-PTT efficiency in vivo as evidenced by highly efficient tumor ablation. Furthermore, the ICG-EPI NPs exhibited inappreciable toxicity. This co-self-assembly of both FDA-approved agents provides a safe and "Molecular economical" strategy in the rational design of multifunctional nano-theranostic systems for real-time self-monitoring intracellular drug delivery and targeting multimodal imaging-guided synergistic combination therapy.

Li Y ，Liu G ，Ma J ，Lin J ，Lin H ，Su G ，Chen D ，Ye S ，Chen X ，Zhu X ，Hou Z ... -  《-》

Multifunctional Mesoporous Polydopamine With Hydrophobic Paclitaxel For Photoacoustic Imaging-Guided Chemo-Photothermal Synergistic Therapy.

Chemo-photothermal therapy has attracted intensive attention because of its low side effects and better therapeutic efficiency. Although many photothermal agents have been loaded with chemotherapeutic drugs for chemo-photothermal therapy, their applications are limited by complex synthetic protocols and long-term safety. Therefore, there is significant clinical value in the development of a simple system of biocompatible and biodegradable photothermal nanomaterials with high payloads of chemotherapeutic drugs for chemo-photothermal synergistic therapy. In this study, PEG-modified polydopamine nanoparticles with mesoporous structure (MPDA-PEG) were successfully obtained by an emulsion-induced interface assembly strategy. Subsequently, paclitaxel (PTX) dissolved in acetone was loaded into the mesoporous channels of MPDA-PEG nanoparticles by solution absorption method. A PTX-loaded MPDA-PEG (MPDA-PEG-PTX) nanoplatform for combination of photothermal therapy (PTT) and chemotherapy was developed. The synthesized MPDA-PEG nanoparticles had a great photothermal effect under near-infrared (NIR) laser irradiation and exhibited an enhanced photothermal effect with the increase of particle size. Meanwhile, MPDA-PEG nanoparticles also had a high payload of PTX, and the PTX release could be greatly accelerated by elevated temperature from photothermal effect. In MTT cytotoxicity assay, A549 cells incubated with MPDA-PEG-PTX under NIR laser irradiation (PTT + chemotherapy group) exhibited better therapeutic effect than single chemotherapy (MPDA-PEG-PTX group) and PTT (MPDA-PEG + Laser group). The synergistic therapeutic effect of MPDA-PEG-PTX with NIR laser irradiation in vivo was further investigated under the guidance of photoacoustic imaging (PAI), tumors of nude mice treated with MPDA-PEG-PTX with NIR laser irradiation were completely eliminated with minimal side effect. The MPDA-PEG-PTX nanoplatform is a simple and effective platform which can completely inhibit tumor growth with minimal side effects under NIR irradiation, and it exhibits better therapeutic effect than single chemotherapy and PTT.

Zhang L ，Yang P ，Guo R ，Sun J ，Xie R ，Yang W ... -  《International Journal of Nanomedicine》