Mussel-inspired "plug-and-play" hydrogel glue for postoperative tumor recurrence and wound infection inhibition.

Currently, clinical tumor resection is faced with two options: open and minimally invasive surgery. Open surgery is easy to completely remove the lesion but is prone to infection, while minimally invasive surgery recovers faster but may cause tumor recurrence. To fill the shortcomings of the two surgical modes and make the choice for tumor resection more effortlessly, we developed a postoperative black phosphorus-Ag nanocomposites-loaded dopamine-modified hyaluronic acid-Pluronic® F127 (BP-Ag@HA-DA-Plu) hydrogel implantation system that can prevent tumor recurrence and wound infection simultaneously. Experiments have shown that the hydrogel system combined with 808 nm near-infrared (NIR) irradiation has excellent anti-tumor, antibacterial, and wound healing abilities. Additionally, unlike existing surgical hydrogel products that require inconvenient in-situ cross-linking, the BP-Ag@HA-DA-Plu hydrogel system offers "plug-and-play" functionality during surgery due to its thermo-responsiveness, injectability, and adhesion, thereby greatly improving the efficiency of surgery.

Self-driven nanoprodrug platform with enhanced ferroptosis for synergistic photothermal-IDO immunotherapy.

Insufficient immune stimulation and stubborn immune resistance are the critical factors limiting tumor immunotherapy. Here, we report a multifunctional nanoprodrug platform with self-driven indoximod (IND) release and oxidative stress amplification. The aim is to awaken immune responses and block the indoleamine 2,3-dioxygenase (IDO) pathway through a combination of ferroptosis, photothermal therapy, and immunotherapy. This nanosystem improved the delivery efficiency of IND due to click chemistry linked ROS responsive prodrug and self-driven drug release. Meanwhile, the tactic of simultaneously increasing ROS and eliminating GSH amplified oxidative stress and strengthened ferroptosis, which further enhanced immunogenicity along with polydopamine-based photothermal therapy. IDO immunization combined with ferroptosis as well as photothermal therapy not only stimulated immune response, but also reversed immune suppression with enhanced immune memory. Therefore, primary tumor, distant tumor, and cancer metastasis were inhibited. This study provides a perspective on immunotherapeutics for cancer treatment.

An injectable hydrogel based on Bi2Se3 nanosheets and hyaluronic acid for chemo-photothermal synergistic therapy.

To resolve poor accumulation caused by systemic administration, injectable and responsive hydrogels are the prospective drug delivery systems for localized tumor treatment, owning to negligible invasiveness and accurate administration. Herein, an injectable hydrogel, based on dopamine (DA) crosslinked hyaluronic acid and Bi2Se3 nanosheets (NSs) loading with doxorubicin (DOX) coated with polydopamine (Bi2Se3-DOX@PDA), was developed for synergistic chem-photothermal cancer therapy. The ultrathin functional Bi2Se3-DOX@PDA NSs could be responsive to the weak acidic condition and photothermal effect under NIR laser irradiation, achieving controlled release of DOX. Moreover, nanocomposite hydrogel based on hyaluronic acid matrix could be precisely administrated through intratumoral injection since its injectability and self-healing capacity, remaining at injected sites for at least 12 days. Furthermore, the excellent therapeutics effect of Bi2Se3-DOX@PDA nanocomposite hydrogel was demonstrated on 4 T1 xenograft tumor with outstanding injectability and negligible systemic side-effect. In short, the construction of Bi2Se3-DOX@PDA nanocomposite hydrogel paves a prospective path for local treatment of cancers.

Mussel-Inspired Ligand Clicking and Ion Coordination on 2D Black Phosphorus for Cancer Multimodal Imaging and Therapy.

As a promising 2D nanocarrier, the biggest challenge of bare black phosphorus nanosheets (BP NSs) lies in the inherent instability, while it can be improved by surface modification strategies to a great extent. Considering the existing infirm BP NSs surface modification strategies, A mussels-inspired strong adhesive biomimetic peptide with azide groups for surface modification to increase the stability of BP NSs is synthesized. The azide groups on the peptide can quickly and precisely bind to the targeting ligand through click chemistry, solving the problem of nonspecificity of secondary modification of other mussel-mimicking materials. Besides, a catechol-Gd3+ coordination network is further constructed for magnetic resonance imaging (MRI) and inducing intracellular endo/lysosome escape. The fabricated BP-DOX@Gd/(DOPA)4 -PEG-TL nanoplatform exhibits enhanced antitumor abilities through synergetic chemo/photothermal effects both in vitro and in vivo.

pH-Sensitive and Charge-Reversal Polymeric Nanoplatform Enhanced Photothermal/Photodynamic Synergistic Therapy for Breast Cancer.

As reported, breast cancer is one of the most common malignancies in women and has overtaken lung cancer as the most commonly diagnosed cancer worldwide by 2020. Currently, phototherapy is a promising anti-tumor therapy due to its fewer side effects, less invasiveness, and lower cost. However, its application in cancer therapeutics is limited by the incomplete therapeutic effect caused by low drug penetration and monotherapy. Herein, we built a charge-reversal nanoplatform (Ce6-PLGA@PDA-PAH-DMMA NPs), including polydopamine (PDA) and chlorin e6 (Ce6) for enhancing photothermal/photodynamic synergistic therapy. The PAH-DMMA charge-reversal layer enabled Ce6-PLGA@PDA-PAH-DMMA NPs to have long blood circulation at the normal physiological environment and to successfully realize charge reversal under the weakly acidic tumor microenvironment, improving cellular uptake. Besides, in vitro tests demonstrated that Ce6-PLGA@PDA-PAH-DMMA NPs had high photothermal conversion and greater anti-tumor activity than no charge-reversal nanoparticles, which overcame the limited tumor therapeutic efficacy of PTT or photodynamic therapy alone. Overall, the design of pH-responsive and charge-reversal nanoparticles (Ce6-PLGA@PDA-PAH-DMMA NPs) provided a promising approach for synergistic PTT/PDT therapy against breast cancer.

A light-weight periodic plate with embedded acoustic black holes and bandgaps for broadband sound radiation reduction.

Conceiving lightweight structures with low vibration and sound radiation properties is an important topic. The concept of Acoustic Black Hole (ABH) offers new impetus to tackle this problem. Most existing ABH structures are based on simple ABH cells. Apart from the reduced structural strength, systematic ABH effects occur typically above the cut-on frequency of the ABH element, which is perceived as a bottlenecking problem. To tackle the problem, this paper examines the sound radiation properties of a plate comprising periodically tangled ABH cells. Through combining ABH effects with sub-wavelength bandgaps (BGs), numerical and experimental studies show that the plate exhibits reduced sound radiation properties in an ultra-broad frequency range, far below the cut-on frequency of an ABH element. This is owing to the tangled nature of the ABH elements, which extends the actual dimension of the ABH, lowers its onset frequency and reduces the sound radiation efficiency through creating slow waves. Inside the BGs, the reduced sound radiation is mainly due to the redistribution of the vibration energy, basically confined to the excitation area. Capitalizing on the combined ABH and BG features alongside improved mechanical properties, the proposed structure shows promise as a light-weight solution for broadband noise reduction.

Charge-reversal biodegradable MSNs for tumor synergetic chemo/photothermal and visualized therapy.

Given the difficulties of biodegradation of mesoporous silica nanoparticles (NPs), enrichment and penetration of tumor sites, and real-time monitoring of the treatment process, we developed a kind of mannose-doping doxorubicin-loading mesoporous silica nanoparticle (MSN-Man-DOX) and coated by polydopamine-Gd3+ (PDAGd) metal-phenolic networks, as well as modified by poly (2-Ethyl-2-Oxazoline) (PEOz), constructing a novel nanomedicine MSN-Man-DOX@PDA-Gd-PEOz. Its pH-responsive charge reversal, photothermal, biodegradation, drug release, and magnetic resonance imaging (MRI) properties were evaluated in vitro. Cellular uptake, tumor penetration, lysosomal escape properties, as well as cell safety and toxicity of the nanoplatform were investigated through cell experiments. Finally, the MRI, organ distribution, photothermal condition, and comprehensive anti-tumor therapy in vivo were evaluated comprehensively through animal experiments. Research results showed that MSN-Man-DOX@PDA-Gd-PEOz had outstanding tumor enrichment and penetration abilities, which can produce excellent treatment effects through the synergistic effect of chemotherapy and photothermal therapy (PTT) with the function of magnetic resonance imaging contrast agent for disease monitoring. Besides, after finishing the therapeutic effect MSN-Man-DOX@PDA-Gd-PEOz can be biodegraded, so it had a good prospect of clinical application.

Charge-reversal nanomedicine based on black phosphorus for the development of A Novel photothermal therapy of oral cancer.

Driven by the lifestyle habits of modern people, such as excessive smoking, drinking, and chewing betel nut and other cancer-causing foods, the incidence of oral cancer has increased sharply and has a trend of becoming younger. Given the current mainstream treatment means of surgical resection will cause serious damage to many oral organs, so that patients lose the ability to chew, speak, and so on, it is urgent to develop new oral cancer treatment methods. Based on the strong killing effect of photothermal therapy on exposed superficial tumors, we developed a pH-responsive charge reversal nanomedicine system for oral cancer which is a kind of classic superficial tumor. With excellent photothermal properties of polydopamine (PDA) modified black phosphorus nanosheets (BP NSs) as basal material, then used polyacrylamide hydrochloride-dimethylmaleic acid (PAH-DMMA) charge reversal system for further surface modification, which can be negatively charged at blood circulation, and become a positive surface charge in the tumor site weakly acidic conditions due to the breaking of dimethylmaleic amide. Therefore, the uptake of oral cancer cells was enhanced and the therapeutic effect was improved. It can be proved that this nanomedicine has excellent photothermal properties and tumor enrichment ability, as well as a good killing effect on oral cancer cells through in vitro cytotoxicity test and in vivo photothermal test, which may become a very promising new model of oral cancer treatment.

Black phosphorus-based nano-drug delivery systems for cancer treatment: Opportunities and challenges.

In this comment, the opportunities of black phosphorus-based nano-drug delivery systems for cancer treatment are highlighted.Image, graphical abstract.

Applications of Surface Modification Technologies in Nanomedicine for Deep Tumor Penetration.

The impermeable barrier of solid tumors due to the complexity of their components limits the treatment effect of nanomedicine and hinders its clinical translation. Several methods are available to increase the penetrability of nanomedicine, yet they are too complex to be effective, operational, or practical. Surface modification employs the characteristics of direct contact between multiphase surfaces to achieve the most direct and efficient penetration of solid tumors. Furthermore, their simple operation makes their use feasible. In this review, the latest surface modification strategies for the penetration of nanomedicine into solid tumors are summarized and classified into "bulldozer strategies" and "mouse strategies." Additionally, the evaluation methods, existing problems, and the development prospects of these technologies are discussed.

Polydopamine-Based "Four-in-One" Versatile Nanoplatforms for Targeted Dual Chemo and Photothermal Synergistic Cancer Therapy.

Abstract: The development of versatile nanoscale drug delivery systems that integrate with multiple therapeutic agents or methods and improve the efficacy of cancer therapy is urgently required. To satisfy this demand, polydopamine (PDA)-modified polymeric nanoplatforms were constructed for the dual loading of chemotherapeutic drugs. The hydrophobic anticancer drug docetaxel (DTX) was loaded into the polymeric nanoparticles (NPs) which were fabricated from the star-shaped copolymer CA-PLGA. Then DTX-loaded NPs were coated with PDA, followed by conjugation of polyelethyl glycol (PEG)-modified targeting ligand aptamer AS1411(Apt) and adsorption of the hydrophilic anticancer drug doxorubicin (DOX). This "four-in-one" nanoplatform, referred to as DTX/NPs@PDA/DOX-PEG-Apt, demonstrated high near-infrared photothermal conversion efficiency and exhibited pH and thermo-responsive drug release behavior. Furthermore, it was able to specifically target MCF-7 human breast carcinoma cells and provide synergistic chemo-photothermal therapy to further improve the anticancer effect both in vitro and in vivo, providing a novel promising strategy for cancer therapy.

pH-Responsive Dual Drug-Loaded Nanocarriers Based on Poly (2-Ethyl-2-Oxazoline) Modified Black Phosphorus Nanosheets for Cancer Chemo/Photothermal Therapy.

Synergistic cancer therapy, such as those combining chemotherapeutic and photothermal methods, has stronger treatment effect than that of individual ones. However, it is challenging to efficiently deliver nanocarriers into tumor cells to elevate intracellular drug concentration. Herein, we developed an effective pH-responsive and dual drug co-delivery platform for combined chemo/photothermal therapy. An anticancer drug doxorubicin (DOX) was first loaded onto the surface of black phosphorus (BP). With poly(2-ethyl-2-oxazoline) (PEOz) ligand conjugated onto the polydopamine (PDA) coated BP nanosheets, targeted long circulation and cellular uptake in vivo was significantly improved. With another anticancer drug bortezomib (BTZ) loaded onto the surface of the nanocapsule, the platform can co-deliver two different drugs. The surface charge of the nanocapsule was reversed from negative to positive at the tumor extracellular pH (∼6.8), ionizing the tertiary amide groups along the PEOz chain, thus facilitating the cell internalization of the nanocarrier. The cytotoxicity therapeutic effect of this nanoplatform was further augmented under near-infrared laser irradiation. As such, our DOX-loaded BP@PDA-PEOz-BTZ platform is very promising to synergistic cancer therapy.

A Versatile Platform Based on Black Phosphorus Nanosheets with Enhanced Stability for Cancer Synergistic Therapy.

Cancer can be effectively treated by photothermal therapy in combination with chemotherapy. Black phosphorus (BP) nanosheets (NSs) have been considered as a promising nanocarrier for synergistic chemo/photothermal therapy. However, the intrinsic instability of bare BP is a great challenge for drug delivery applications. Herein, we coated the BP NSs with polydopamine (PDA), and prepared a novel nanocapsule BP@PDA-PEG-FA that was modified with targeting polymer mercapto group-poly(ethylene glycol)-folic acid (HS-PEG-FA). The nanocapsule was loaded with doxorubicin (DOX) as a model drug for cervical cancer therapy. This BP-based drug delivery system exhibited enhanced stability, significantly high photothermal efficiency, and targeting ability for cancer cells. Furthermore, DOX was released from the DOX-loaded BP NSs in a tumor microenvironment at low pH under near-infrared (NIR) laser irradiation, demonstrating the effects of synergistic therapy. Both in vitro and in vivo experiments proved that the synergistic therapy combining chemotherapy with photothermal therapy had high biocompatibility, outstanding antitumor efficacy and potential clinical application.

TPGS-Functionalized Polydopamine-Modified Mesoporous Silica as Drug Nanocarriers for Enhanced Lung Cancer Chemotherapy against Multidrug Resistance.

A nanocarrier system of d-a-tocopheryl polyethylene glycol 1000 succinate (TPGS)-functionalized polydopamine-coated mesoporous silica nanoparticles (NPs) is developed for sustainable and pH-responsive delivery of doxorubicin (DOX) as a model drug for the treatment of drug-resistant nonsmall cell lung cancer. Such nanoparticles are of desired particle size, drug loading, and drug release profile. The surface morphology, surface charge, and surface chemical properties are also successfully characterized by a series of techniques such as transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), Brunauer-Emmett-Teller (BET) method, thermal gravimetric analysis (TGA), dynamic light scattering (DLS), and Fourier transform infrared spectroscopy (FTIR). The normal A549 cells and drug-resistant A549 cells are employed to access the cytotoxicity and cellular uptake of the NPs. The therapeutic effects of TPGS-conjugated nanoparticles are evaluated in vitro and in vivo. Compared with free DOX and DOX-loaded NPs without TPGS ligand modification, MSNs-DOX@PDA-TPGS exhibits outstanding capacity to overcome multidrug resistance and shows better in vivo therapeutic efficacy. This splendid drug delivery platform can also be sued to deliver other hydrophilic and hydrophobic drugs.