Proof-of-Concept Study of Multifunctional Hybrid Nanoparticle System Combined with NIR Laser Irradiation for the Treatment of Melanoma.

The global impact of cancer emphasizes the importance of developing innovative, effective and minimally invasive therapies. In the context of superficial cancers, the development of a multifunctional nanoparticle-based system and its in vitro and in vivo safety and efficacy characterization are, herein, proposed as a proof-of-concept. This multifunctional system consists of gold nanoparticles coated with hyaluronic and oleic acids, and functionalized with epidermal growth factor for greater specificity towards cutaneous melanoma cells. This nanoparticle system is activated by a near-infrared laser. The characterization of this nanoparticle system included several phases, with in vitro assays being firstly performed to assess the safety of gold nanoparticles without laser irradiation. Then, hairless immunocompromised mice were selected for a xenograft model upon inoculation of A375 human melanoma cells. Treatment with near-infrared laser irradiation for five minutes combined with in situ administration of the nanoparticles showed a tumor volume reduction of approximately 80% and, in some cases, led to the formation of several necrotic foci, observed histologically. No significant skin erythema at the irradiation zone was verified, nor other harmful effects on the excised organs. In conclusion, these assays suggest that this system is safe and shows promising results for the treatment of superficial melanoma.

A Smart Multifunctional Nanoparticle for Enhanced Near-Infrared Image-Guided Photothermal Therapy Against Gastric Cancer.

BACKGROUND: Surgery is considered to be a potentially curative approach for gastric cancer. However, most cases are diagnosed at a very advanced stage for the lack of typical symptoms in the initial stage, which makes it difficult to completely surgical resect of tumors. Early diagnosis and precise personalized intervention are urgent issues to be solved for improving the prognosis of gastric cancer. Herein, we developed an RGD-modified ROS-responsive multifunctional nanosystem for near-infrared (NIR) imaging and photothermal therapy (PTT) against gastric cancer. METHODS: Firstly, the amphiphilic polymer was synthesized by bromination reaction and nucleophilic substitution reaction of carboxymethyl chitosan (CMCh) and 4-hydroxymethyl-pinacol phenylborate (BAPE). Then, it was used to encapsulate indocyanine green (ICG) and modified with RGD to form a smart multifunctional nanoparticle targeted to gastric cancer (CMCh-BAPE-RGD@ICG). The characteristics were determined, and the targeting capacity and biosafety were evaluated both in vitro and in vivo. Furthermore, CMCh-BAPE-RGD@ICG mediated photothermal therapy (PTT) effect was studied using gastric cancer cells (SGC7901) and SGC7901 tumor model. RESULTS: The nanoparticle exhibited suitable size (≈ 120 nm), improved aqueous stability, ROS-responsive drug release, excellent photothermal conversion efficiency, enhanced cellular uptake, and targeting capacity to tumors. Remarkably, in vivo studies suggested that CMCh-BAPE-RGD@ICG could accurately illustrate the location and margin of the SGC7901 tumor through NIR imaging in comparison with non-targeted nanoparticles. Moreover, the antitumor activity of CMCh-BAPE-RGD@ICG-mediated PTT could effectively suppress tumor growth by inducing necrosis and apoptosis in cancer cells. Additionally, CMCh-BAPE-RGD@ICG demonstrated excellent biosafety both in vitro and in vivo. CONCLUSION: Overall, our study provides a biocompatible theranostic nanoparticle with enhanced tumor-targeting ability and accumulation to realize NIR image-guided PTT in gastric cancer.

Magneto-plasmonic nanostars for image-guided and NIR-triggered drug delivery.

Smart multifunctional nanoparticles with magnetic and plasmonic properties assembled on a single nanoplatform are promising for various biomedical applications. Owing to their expanding imaging and therapeutic capabilities in response to external stimuli, they have been explored for on-demand drug delivery, image-guided drug delivery, and simultaneous diagnostic and therapeutic (i.e. theranostic) applications. In this study, we engineered nanoparticles with unique morphology consisting of a superparamagnetic iron oxide core and star-shaped plasmonic shell with high-aspect-ratio gold branches. Strong magnetic and near-infrared (NIR)-responsive plasmonic properties of the engineered nanostars enabled multimodal quantitative imaging combining advantageous functions of magnetic resonance imaging (MRI), magnetic particle imaging (MPI), photoacoustic imaging (PAI), and image-guided drug delivery with a tunable drug release capacity. The model drug molecules bound to the core-shell nanostars were released upon NIR illumination due to the heat generation from the core-shell nanostars. Moreover, our simulation analysis showed that the specific design of the core-shell nanostars demonstrated a pronounced multipolar plasmon resonance, which has not been observed in previous reports. The multimodal imaging and NIR-triggered drug release capabilities of the proposed nanoplatform verify their potential for precise and controllable drug release with different applications in personalized medicine.

Hypoxia-Targeting Multifunctional Nanoparticles for Sensitized Chemotherapy and Phototherapy in Head and Neck Squamous Cell Carcinoma.

PURPOSE: Chemotherapy in head and neck squamous cell carcinoma (HNSCC) has many systemic side effects, as well as hypoxia-induced chemoresistance. To reduce side effects and enhance chemosensitivity are urgently needed. METHODS: We synthesized a drug delivery system (named CECMa NPs) based on cisplatin (CDDP) and metformin (chemotherapeutic sensitizer), of which chlorin e6 (Ce6) and polyethylene glycol diamine (PEG) were synthesized as the shell, an anti-LDLR antibody (which can target to hypoxic tumor cells) was modified on the surface to achieve tumor targeting. RESULTS: The NPs possessed a great synergistic effect of chemotherapy and phototherapy. After laser stimulation, both CDDP and metformin can be released in situ to achieve anti-tumor effects. Meanwhile, PDT and PTT triggered by a laser have anticancer effects. Furthermore, compared with free cisplatin, CECMa exhibits less systemic toxicity with laser irradiation in the xenograft mouse tumor model. CONCLUSION: CECMa effectively destroyed the tumors via hypoxia targeting multimodal therapy both in vitro and in vivo, thereby providing a novel strategy for targeting head and neck squamous cell carcinoma.

A disassembling strategy overcomes the EPR effect and renal clearance dilemma of the multifunctional theranostic nanoparticles for cancer therapy.

Despite multifunctional nanoparticles using for photothermal therapy can efficiently kill cancer cells, their further application is still hindered by the intrinsic high uptake in the reticuloendothelial system (RES) organs, causing the slow elimination from the body and potential toxicity to the body. Therefore, it is ideal to develop multifunctional nanoparticles which process the ability to effectively accumulate in tumors, while the nanoparticles can be rapidly excreted from the body via renal clearance after effective treatment. Herein, we report the multifunctional nanoparticles (FeTNPs) based on the coordination interaction of phenolic group and metal iron, which are composed of ferric iron, tannic acid (TA) and poly (glutamic acid)-graft-methoxypoly (ethylene glycol) (PLG-g-mPEG). FeTNPs exhibit the following highlighted features: (1) The effective accumulation in the tumor tissue is achieved based on EPR effect. (2) The dual photoacoustic (PA)/magnetic resonance (MR) imaging capacity can provide guidance for the photothermal therapy (PTT). (3) FeTNPs can be dynamically disassembled by deferoxamine mesylate (DFO) to accelerate elimination of the nanoparticles, thus reducing the potential toxicity for the body. The DFO triggered dynamic disassembling strategy may open a new avenue to overcome the dilemma between EPR effect and renal clearance.