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.

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 near-infrared-photoresponsive shape memory implants based on black phosphorus nanofillers.

In this paper, we propose a new shape memory polymer (SMP) composite with excellent near-infrared (NIR)-photoresponsive shape memory performance and biodegradability. The composite is fabricated by using piperazine-based polyurethane (PU) as thermo-responsive SMP incorporated with black-phosphorus (BP) sheets as NIR photothermal nanofillers. Under 808 nm light irradiation, the incorporated BP sheets with concentration of only 0.08 wt% enable rapid temperature increase over the glass temperature of PU and trigger the shape change of the composite with shape recovery rate of ∼100%. The in vitro and in vivo toxicity examinations demonstrate the good biocompatibility of the PU/BP composite, and it degrades naturally into non-toxic carbon dioxide and water from PU and non-toxic phosphate from BP. By implanting PU/BP columns into back subcutis and vagina of mice, they exhibit excellent shape memory activity to change their shape quickly under moderate 808 nm light irradiaiton. Such SMP composite enable the development of intelligent implantable devices, which can be easily controlled by the remote NIR light and degrade gradually after performing the designed functions in the body.

Near-infrared light-triggered drug delivery system based on black phosphorus for in vivo bone regeneration.

A near-infrared (NIR) light-triggered drug delivery platform is produced by incorporating SrCl2 and BP nanosheets (BPs) into poly(lactic-co-glycolic acid) (PLGA) for bone regeneration. The fabricated BP-SrCl2/PLGA microspheres show efficient NIR absorption and photothermal effects due to the BPs. The NIR-triggered release behavior of Sr2+ by flawing the PLGA shells is investigated and the microspheres exhibit excellent cell viability and biodegradability. Implantation of the BP-SrCl2/PLGA microspheres into a rat femoral defect demonstrates good tissue compatibility and excellent bone regeneration capacity under NIR light irradiation. Our study indicates that local release of Sr2+ at optimal time periods controlled by NIR irradiation improves bone regeneration significantly and this NIR-triggered drug delivery system composed of BPs is suitable for therapies requiring precise control at specific time.

PLLA nanofibrous paper-based plasmonic substrate with tailored hydrophilicity for focusing SERS detection.

We report a new paper-based surface enhanced Raman scattering (SERS) substrate platform contributed by a poly(l-lactic acid) (PLLA) nanofibrous paper adsorbed with plasmonic nanostructures, which can circumvent many challenges of the existing SERS substrates. This PLLA nanofibrous paper has three-dimensional porous structure, extremely clean surface with good hydrophobicity (contact angle is as high as 133.4°), and negligible background interference under Raman laser excitation. Due to the strong electrostatic interaction between PLLA nanofiber and cetyltrimethylammonium bromide (CTAB) molecules, the CTAB-coated gold nanorods (GNRs) are efficiently immobilized onto the fibers. Such a hydrophobic paper substrate with locally hydrophilic SERS-active area can confine analyte molecules and prevent the random spreading of molecules. The confinement leads to focusing effect and the GNRs-PLLA SERS substrate is found to be highly sensitive (0.1 nM Rhodamine 6G and malachite green) and exhibit excellent reproducibility (∼8% relative standard deviation (RSD)) and long-term stability. Furthermore, it is also cost-efficient, with simple fabrication methodology, and demonstrates high sample collection efficiency. All of these benefits ensure that this GNRs-PLLA substrate is a really perfect choice for a variety of SERS applications.

Nanomechanical properties of poly(l-lactide) nanofibers after deformation.

Atomic force microscopy (AFM) technique was used to investigate the nanomechanical properties of poly(l-lactide) (PLLA) nanofibers produced by the thermally induced phase separation (TIPS) method. Firstly, AFM-based nanolithography was employed to produce localized deformations on the surface of single PLLA nanofiber, in which the AFM tip served as a nanoscale burin to draw a scratch longitudinally along the nanofiber. Secondly, the morphology and physical properties of the nanofiber before and immediately after the deformation were characterized with AFM and force spectroscopy measurement. During the initial stage of TIPS process, the crystallization of PLLA resulted in a regular arrangement of crystalline domains along the thinner fibrils which then assembled laterally into larger nanofibers. The deformation due to the nanoindentation and plowing with the probe induced structural variation of PLLA nanofibers and led to a functional consequence in their nanomechanical properties. The region after deformation had a higher adhesion force and elastic modulus, probably because the polymer chains became more compact and ordered under both compression and shear stresses.