Self-Heating Multistage Microneedle Patch for Topical Therapy of Skin Cancer.

Topical therapy is a favored route for treating skin cancers, but remain many challenges, such as low delivery efficiency, limited tumor tissue penetration, and unsatisfactory blood circulation. Here, a self-heating microneedle (MN) patch with multilevel structures, including a dissolvable base for rapid drug release, a degradable tip for sustained drug release, and a self-heating substrate is described. The thermally enhanced drug release performance is validated through both in vitro and in vivo experiments. High tumor therapeutic efficacy can be achieved due to the rapid release of 5-fluorouracil, while the sustained release of thymoquinone endows the MN patch with long-term tumor inhibition ability. It is further demonstrated the feasibility of such an MN patch for in vivo topical therapy of cutaneous squamous cell carcinoma with high efficacy, low side effects, and long-term inhibition of recurrence. This self-heating MN patch holds great promise for potential clinical applications, especially for the treatment of skin cancers.

Niobium Diselenide Nanosheets: An Emerging Biodegradable Nanoplatform for Efficient Cancer Phototheranostics in the NIR-II Window.

As a prominent class of 2D transition metal dichalcogenides (TMDCs), niobium diselenide nanosheets (NbSe2 NSs) have garnered tremendous interest on account of promising applications pertaining to optoelectronics and energy storage. Although NbSe2 NSs have many unique advantages such as inherent biocompatibility and broad absorption in the NIR region, their biomedical applications have rarely been reported, especially as therapeutic agents for the second near-infrared (NIR-II) range. Herein, a biodegradable nanotherapeutic platform consisting of NbSe2 NSs is designed and demonstrated for NIR-II light-triggered photothermal therapy. NbSe2 NSs synthesized by grinding and liquid exfoliation exhibit superior photothermal conversion efficiency (48.3%) and remarkable photothermal stability in the NIR-II region. In vitro assessment demonstrates that NbSe2 NSs have favorable photothermal cell ablation efficiency and biocompatibility. After intravenous injection in vivo, the NbSe2 NSs accumulate passively in tumor sites to facilitate fluorescence imaging and tumor ablation by NIR-II illumination. Furthermore, as a result of gradual degradation in the physiological environment, NbSe2 NSs can be excreted from the body to avoid potential toxicity caused by long-term retention in vivo. The results reveal a promising NIR-II light-triggered PTT strategy with the aid of NbSe2 NSs and the platform is expected to have large potential in cancer theranostics.

Modular polymer platform as a novel approach to head and neck cancer therapy.

Head and neck cancer is the sixth most common cancer in the world, with more than 300,000 deaths attributed to the disease annually. Aggressive surgical resection often with adjuvant chemoradiation is the cornerstone of treatment. However, the necessary chemoradiation treatment can result in collateral damage to adjacent vital structures causing a profound impact on quality of life. Here, we present a novel polymer of poly(lactic-co-glycolic) acid and polyvinyl alcohol that can serve as a versatile multidrug delivery platform as well as for detection on cross-sectional imaging while functioning as a fiduciary marker for postoperative radiotherapy and radiotherapeutic dosing. In a mouse xenograft model, the dual-layered polymer composed of calcium carbonate/thymoquinone was used for both polymer localization and narrow-field infusion of a natural therapeutic compound. A similar approach can be applied in the treatment of head and neck cancer patients, where immunotherapy and traditional chemotherapy can be delivered simultaneously with independent release kinetics.

Biodegradable Bi2 O2 Se Quantum Dots for Photoacoustic Imaging-Guided Cancer Photothermal Therapy.

As new 2D layered nanomaterials, Bi2 O2 Se nanoplates have unique semiconducting properties that can benefit biomedical applications. Herein, a facile top-down approach for the synthesis of Bi2 O2 Se quantum dots (QDs) in a solution is described. The Bi2 O2 Se QDs with a size of 3.8 nm and thickness of 1.9 nm exhibit a high photothermal conversion coefficient of 35.7% and good photothermal stability. In vitro and in vivo assessments demonstrate that the Bi2 O2 Se QDs possess excellent photoacoustic (PA) performance and photothermal therapy (PTT) efficiency. After systemic administration, the Bi2 O2 Se QDs accumulate passively in tumors enabling efficient PA imaging of the entire tumors to facilitate imaging-guided PTT without obvious toxicity. Furthermore, the Bi2 O2 Se QDs which exhibit degradability in aqueous media not only have sufficient stability during in vivo circulation to perform the designed therapeutic functions, but also can be discharged harmlessly from the body afterward. The results reveal the great potential of Bi2 O2 Se QDs as a biodegradable multifunctional agent in medical applications.

Black Phosphorus-Based Multimodal Nanoagent: Showing Targeted Combinatory Therapeutics against Cancer Metastasis.

In breast cancer chemophotothermal therapy, it is a great challenge for the development of multifunctional nanoagents for precision targeting and the effective treatment of tumors, especially for metastasis. Herein, we successfully design and synthesize a multifunctional black phosphorus (BP)-based nanoagent, BP/DTX@PLGA, to address this challenge. In this composite nanoagent, BP quantum dots (BPQDs) are loaded into poly(lactic-co-glycolic acid) (PLGA) with additional conjugation of a chemotherapeutic agent, docetaxel (DTX). The in vivo distribution results demonstrate that BP/DTX@PLGA shows striking tropism for targeting both primary tumors and lung metastatic tumors. Moreover, BP/DTX@PLGA exhibits outstanding controllable chemophotothermal combinatory therapeutics, which dramatically improves the efficacy of photothermal tumor ablation when combined with near-light irradiation. Mechanistically, accelerated DTX release from the nanocomplex upon heating and thermal treatment per se synergistically incurs apoptosis-dependent cell death, resulting in the elimination of lung metastasis. Meanwhile, in vitro and in vivo results further confirm that BP/DTX@PLGA possesses good biocompatibility. This study provides a promising BP-based multimodal nanoagent to constrain cancer metastasis.

Black-Phosphorus-Incorporated Hydrogel as a Sprayable and Biodegradable Photothermal Platform for Postsurgical Treatment of Cancer.

Photothermal therapy (PTT) is a fledgling therapeutic strategy for cancer treatment with minimal invasiveness but clinical adoption has been stifled by concerns such as insufficient biodegradability of the PTT agents and lack of an efficient delivery system. Here, black phosphorus (BP) nanosheets are incorporated with a thermosensitive hydrogel [poly(d,l-lactide)-poly(ethylene glycol)-poly(d,l-lactide) (PDLLA-PEG-PDLLA: PLEL)] to produce a new PTT system for postoperative treatment of cancer. The BP@PLEL hydrogel exhibits excellent near infrared (NIR) photothermal performance and a rapid NIR-induced sol-gel transition as well as good biodegradability and biocompatibility in vitro and in vivo. Based on these merits, an in vivo PTT postoperative treatment strategy is established. Under NIR irradiation, the sprayed BP@PLEL hydrogel enables rapid gelation forming a gelled membrane on wounds and offers high PTT efficacy to eliminate residual tumor tissues after tumor removal surgery. Furthermore, the good photothermal antibacterial performance prevents infection and this efficient and biodegradable PTT system is very promising in postoperative treatment of cancer.

2D Material-Based Nanofibrous Membrane for Photothermal Cancer Therapy.

One of the clinical challenges facing photothermal cancer therapy is health risks imposed by the photothermal nanoagents in vivo. Herein, a photothermal therapy (PTT) platform composed of a 2D material-based nanofibrous membrane as the agent to deliver thermal energy to tumors under near-infrared (NIR) light irradiation is described. The photothermal membrane, which is fabricated by an electrospinning poly(l-lactic acid) (PLLA) nanofibrous membrane loaded with bismuth selenide (Bi2Se3) nanoplates, exhibits very high photothermal conversion efficiency and long-term stability. Cell experiments and hematological analyses demonstrate that the Bi2Se3/PLLA membranes have excellent biocompatibility and low toxicity. PTT experiments performed in vivo with the Bi2Se3/PLLA membrane covering the tumor and NIR irradiation produce local hyperthermia to ablate the tumor with high efficiency. Different from the traditional systematical and local injection techniques, this membrane-based PTT platform is promising in photothermal cancer therapy, especially suitable for the treatment of multiple solid tumors or skin cancers, and long-term prevention of cancer recurrence after surgery or PTT, while eliminating the health hazards of nanoagents.

Cell-borne 2D nanomaterials for efficient cancer targeting and photothermal therapy.

Two of the challenges for clinical implementation of nano-therapeutic strategies are optimization of tumor targeting and clearance of the nanoagents in vivo. Herein, a cell-mediated therapy by transporting 2D Bi2Se3 nanosheets within macrophage vehicles is described. The Bi2Se3 nanosheets with excellent near-infrared photothermal performance exhibit high macrophage uptake and negligible cytotoxicity thus facilitating the fabrication of Bi2Se3-laden-macrophages. Compared with bare Bi2Se3, the Bi2Se3-laden-macrophages after intravenous injection show prolonged blood circulation and can overcome the hypoxia-associated drug delivery barrier to target the tumor efficiently and dramatically enhance the efficiency of photothermal cancer therapy. The Bi2Se3-laden-macrophages possess good biocompatibility as demonstrated by the biochemical and histological analyses and furthermore, most of the materials are excreted from the body within 25 days. Our findings reveal a desirable system for highly efficient near-infrared photothermal cancer therapy.

Biodegradable black phosphorus-based nanospheres for in vivo photothermal cancer therapy.

Photothermal therapy (PTT) offers many advantages such as high efficiency and minimal invasiveness, but clinical adoption of PTT nanoagents have been stifled by unresolved concerns such as the biodegradability as well as long-term toxicity. Herein, poly (lactic-co-glycolic acid) (PLGA) loaded with black phosphorus quantum dots (BPQDs) is processed by an emulsion method to produce biodegradable BPQDs/PLGA nanospheres. The hydrophobic PLGA not only isolates the interior BPQDs from oxygen and water to enhance the photothermal stability, but also control the degradation rate of the BPQDs. The in vitro and in vivo experiments demonstrate that the BPQDs/PLGA nanospheres have inappreciable toxicity and good biocompatibility, and possess excellent PTT efficiency and tumour targeting ability as evidenced by highly efficient tumour ablation under near infrared (NIR) laser illumination. These BP-based nanospheres combine biodegradability and biocompatibility with high PTT efficiency, thus promising high clinical potential.

Metabolizable Ultrathin Bi2 Se3 Nanosheets in Imaging-Guided Photothermal Therapy.

Poly(vinylpyrrolidone)-encapsulated Bi2 Se3 nanosheets with a thickness of 1.7 nm and diameter of 31.4 nm are prepared by a solution method. Possessing an extinction coefficient of 11.5 L g(-1) cm(-1) at 808 nm, the ultrathin Bi2 Se3 nanosheets boast a high photothermal conversion efficiency of 34.6% and excellent photoacoustic performance. After systemic administration, the Bi2 Se3 nanosheets with the proper size and surface properties accumulate passively in tumors enabling efficient photoacoustic imaging of the entire tumors to facilitate photothermal cancer therapy. In vivo biodistribution studies reveal that they are expelled from the body efficiently after 30 d. The ultrathin Bi2 Se3 nanosheets have large clinical potential as metabolizable near-infrared-triggered theranostic agents.

Ultrasmall Black Phosphorus Quantum Dots: Synthesis and Use as Photothermal Agents.

Black phosphorus quantum dots (BPQDs) were synthesized using a liquid exfoliation method that combined probe sonication and bath sonication. With a lateral size of approximately 2.6 nm and a thickness of about 1.5 nm, the ultrasmall BPQDs exhibited an excellent NIR photothermal performance with a large extinction coefficient of 14.8 L g(-1) cm(-1) at 808 nm, a photothermal conversion efficiency of 28.4%, as well as good photostability. After PEG conjugation, the BPQDs showed enhanced stability in physiological medium, and there was no observable toxicity to different types of cells. NIR photoexcitation of the BPQDs in the presence of C6 and MCF7 cancer cells led to significant cell death, suggesting that the nanoparticles have large potential as photothermal agents.